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Long Term Safety and Efficacy Study of Tanezumab in Subjects With Osteoarthritis of the Hip or Knee

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ClinicalTrials.gov Identifier: NCT02528188
Recruitment Status : Completed
First Posted : August 19, 2015
Results First Posted : January 10, 2020
Last Update Posted : January 10, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Chronic Pain
Osteoarthritis, Hip
Osteoarthritis, Knee
Interventions Drug: NSAID
Biological: Tanezumab 2.5 mg
Biological: Tanezumab 5 mg
Enrollment 3021
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56. Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56. Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Period Title: Overall Study
Started 1008 1005 1008
Treated 1002 998 996
Completed 741 729 757
Not Completed 267 276 251
Reason Not Completed
Adverse Event             23             22             8
Protocol Violation             4             6             4
Lack of Efficacy             19             21             22
Withdrawal by Subject             97             104             100
Lost to Follow-up             25             21             31
Death             4             4             0
Other             89             91             74
Randomized but not treated             6             7             12
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID Total
Hide Arm/Group Description Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56. Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56. Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48. Total of all reporting groups
Overall Number of Baseline Participants 1002 998 996 2996
Hide Baseline Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1002 participants 998 participants 996 participants 2996 participants
60.30  (9.17) 61.15  (9.57) 60.25  (9.46) 60.57  (9.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1002 participants 998 participants 996 participants 2996 participants
Female
637
  63.6%
654
  65.5%
662
  66.5%
1953
  65.2%
Male
365
  36.4%
344
  34.5%
334
  33.5%
1043
  34.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1002 participants 998 participants 996 participants 2996 participants
White
705
  70.4%
712
  71.3%
680
  68.3%
2097
  70.0%
Black or African American
166
  16.6%
162
  16.2%
186
  18.7%
514
  17.2%
Asian
110
  11.0%
95
   9.5%
99
   9.9%
304
  10.1%
Other
21
   2.1%
29
   2.9%
31
   3.1%
81
   2.7%
1.Primary Outcome
Title Percentage of Participants With Adjudicated Primary Composite Joint Safety Outcome
Hide Description Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive osteoarthritis (OA) type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of joint space width (JSW) (greater than or equal to [>=] 2 millimeters [mm]) within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.9
(2.8 to 5.3)
7.1
(5.6 to 8.9)
1.5
(0.8 to 2.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.39
Confidence Interval (2-Sided) 95%
0.58 to 4.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.61
Confidence Interval (2-Sided) 95%
3.55 to 8.14
Estimation Comments [Not Specified]
2.Primary Outcome
Title Observation Time-Adjusted Event Rate of Participants With Adjudicated Primary Composite Joint Safety Outcome
Hide Description Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Primary joint safety outcome included participants with adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 1000 participant-years
38.3
(28.0 to 52.5)
71.5
(56.7 to 90.2)
14.8
(8.9 to 24.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 23.5
Confidence Interval (2-Sided) 95%
9.3 to 37.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 56.7
Confidence Interval (2-Sided) 95%
38.4 to 74.9
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16
Hide Description WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions, which may not be a whole (integer) number, scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.22  (0.11) -3.33  (0.11) -3.07  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis P-Value 0.0148
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.46 to -0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. Analysis of covariance (ANCOVA) model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis P-Value 0.1597
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.36 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
Hide Description WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.27  (0.11) -3.39  (0.11) -3.08  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis P-Value 0.0030
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.52 to -0.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis P-Value 0.0691
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.40 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16
Hide Description PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using Interactive Response Technology (IRT), where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.96  (0.04) -0.97  (0.04) -0.94  (0.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis P-Value 0.3431
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.11 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis P-Value 0.6332
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.09 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Adjudicated Secondary Composite Joint Safety Outcome
Hide Description Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.0
(0.5 to 1.8)
2.2
(1.4 to 3.3)
0.5
(0.2 to 1.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4082
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.75 to 2.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0238
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
0.31 to 3.63
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Observation Time-Adjusted Event Rate of Participants With Adjudicated Secondary Composite Joint Safety Outcome
Hide Description Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Secondary joint safety outcome included primary osteonecrosis, rapidly progressive OA (type-2), subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 1000 participant-years
9.7
(5.2 to 18.1)
21.8
(14.4 to 33.1)
4.9
(2.1 to 11.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2035
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 4.8
Confidence Interval (2-Sided) 95%
-2.6 to 12.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 16.9
Confidence Interval (2-Sided) 95%
6.8 to 27.0
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Individual Adjudicated Joint Safety Outcome
Hide Description Any participant with incidence of an adjudicated outcome of rapidly progressive OA (type-1 only), rapidly progressive OA (type-2 only), rapidly progressive OA (type-1 or type-2 combined), subchondral insufficiency fracture, primary osteonecrosis, and pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of JSW >=2 mm within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Rapidly Progressive OA Type 1 or 2
3.2
(2.2 to 4.5)
6.3
(4.9 to 8.0)
1.2
(0.6 to 2.1)
Rapidly Progressive OA type 1
2.9
(1.9 to 4.1)
4.9
(3.7 to 6.4)
1.1
(0.6 to 2.0)
Rapidly Progressive OA type 2
0.3
(0.1 to 0.9)
1.4
(0.8 to 2.3)
0.1
(0.0 to 0.6)
Primary Osteonecrosis
0.1
(0.0 to 0.6)
0.1
(0.0 to 0.6)
0
(0.0 to 0.4)
Pathological Fracture
0
(0.0 to 0.4)
0
(0.0 to 0.4)
0
(0.0 to 0.4)
Subchondral Insufficiency Fracture
0.6
(0.2 to 1.3)
0.7
(0.3 to 1.4)
0.4
(0.1 to 1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Rapidly progressive OA Type 1 or 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0248
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference
Estimated Value 1.99
Confidence Interval (2-Sided) 95%
0.31 to 4.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Rapidly Progressive OA Type 1 or 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 5.11
Confidence Interval (2-Sided) 95%
3.16 to 7.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Rapidly Progressive OA Type 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0366
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 1.79
Confidence Interval (2-Sided) 95%
0.16 to 3.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Rapidly Progressive OA Type 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 3.81
Confidence Interval (2-Sided) 95%
1.99 to 6.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Rapidly Progressive OA Type 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6168
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
-0.76 to 1.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Rapidly Progressive OA Type 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0388
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.17 to 2.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Primary osteonecrosis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7245
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.74 to 1.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Primary osteonecrosis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7182
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.74 to 1.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Subchondral insufficiency fracture
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6824
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
-0.96 to 1.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Subchondral insufficiency fracture
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5632
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-0.86 to 2.03
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Observation Time-Adjusted Event Rate of Participants With Individual Adjudicated Joint Safety Outcome
Hide Description Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Individual joint safety outcome included rapidly progressive OA (type-1 only), rapidly progressive OA (type-2 only), rapidly progressive OA (type-1 or type-2 combined), subchondral insufficiency fracture, primary osteonecrosis, and pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 1000 participant-years
Rapidly Progressive OA Type 1 or 2
31.4
(22.2 to 44.4)
63.3
(49.5 to 81.1)
11.9
(6.7 to 20.9)
Rapidly Progressive OA Type 1
28.4
(19.8 to 40.9)
49.1
(37.1 to 65.0)
10.9
(6.0 to 19.6)
Rapidly Progressive OA Type 2
2.9
(0.9 to 9.1)
13.9
(8.2 to 23.4)
1.0
(0.1 to 7.0)
Primary Osteonecrosis
1.0
(0.1 to 6.9)
1.0
(0.1 to 7.0)
0 [1] 
(NA to NA)
Pathological Fracture
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
Subchondral Insufficiency Fracture
5.8
(2.6 to 13.0)
6.9
(3.3 to 14.5)
3.9
(1.5 to 10.5)
[1]
95% CI was not estimable since no participants had events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Rapidly Progressive OA Type 1 or 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 19.56
Confidence Interval (2-Sided) 95%
6.78 to 32.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Rapidly Progressive OA Type 1 or 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 51.48
Confidence Interval (2-Sided) 95%
34.47 to 68.50
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Rapidly Progressive OA Type 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0047
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 17.58
Confidence Interval (2-Sided) 95%
5.39 to 29.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Rapidly Progressive OA Type 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 38.22
Confidence Interval (2-Sided) 95%
23.05 to 53.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Rapidly Progressive OA Type 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3214
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
-1.89 to 5.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Rapidly Progressive OA Type 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 12.88
Confidence Interval (2-Sided) 95%
5.36 to 20.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Subchondral Insufficiency Fracture
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5394
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
-4.17 to 7.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Subchondral Insufficiency Fracture
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3636
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 2.98
Confidence Interval (2-Sided) 95%
-3.44 to 9.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Primary osteonecrosis
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Poisson model for rate difference
Estimated Value 1.0
Estimation Comments 95% CI was not estimable since there were less number of participants with events.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Primary osteonecrosis
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 1.0
Estimation Comments 95% CI was not estimable since there were less number of participants with events.
10.Secondary Outcome
Title Percentage of Participants With Total Joint Replacement or Adjudicated Primary Composite Joint Safety Outcome
Hide Description Percentage of participants with total joint replacement (hip, knee or shoulder) or adjudicated primary composite joint safety outcomes were reported. Adjudicated primary composite joint safety outcomes included primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.6
(6.9 to 10.5)
13.1
(11.1 to 15.4)
3.7
(2.6 to 5.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The event of adjudicated primary osteonecrosis in the tanezumab 2.5 mg treatment group is not included in this analysis. Conclusions for this analysis do not change as the comparison to NSAID is already statistically significant in favor of NSAID.
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 4.87
Confidence Interval (2-Sided) 95%
2.43 to 7.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact methods for risk difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 9.41
Confidence Interval (2-Sided) 95%
6.73 to 12.52
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Observation Time-Adjusted Event Rate of Participants With Total Joint Replacement or Adjudicated Primary Composite Joint Safety Outcome
Hide Description Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Adjudicated primary composite joint safety outcomes included primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame Baseline up to Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 1000 participant-years
84.9
(68.7 to 104.9)
132.5
(111.7 to 157.3)
36.7
(26.6 to 50.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The event of adjudicated primary osteonecrosis in the tanezumab 2.5 mg treatment group is not included in this analysis. Conclusions for this analysis do not change as the comparison to NSAID is already statistically significant in favor of NSAID.
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 48.25
Confidence Interval (2-Sided) 95%
26.76 to 69.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Poisson model for rate difference
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 95.83
Confidence Interval (2-Sided) 95%
70.25 to 121.42
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Medial or Lateral Joint Space Width of the Index Knee (Kellgren-Lawrence Grade 2 or 3) at Weeks 56 and 80
Hide Description Change from baseline in JSW was defined as change in JSW compared to baseline in participants with Kellgren-Lawrence grade 2 or 3 over the course of the study. It was measured radiographically in the medial and lateral tibiofemoral of knee in participants with OA. Kellgren-Lawrence grade system was a method of classifying the severity of knee OA using five grades i.e. 0 [no radiographic features of OA], 1 [doubtful joint space narrowing (JSN) and possible osteophytic lipping], 2 [definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph], 3 [multiple osteophytes, definite JSN, sclerosis, possible bony deformity], 4 [large osteophytes, marked JSN, severe sclerosis and definite bony deformity]. Higher grade indicating worse knee function. The number of participants with progression of OA in the index knee are summarized separately by the compartment of OA at baseline (medial or lateral).
Time Frame Baseline, Weeks 56 and 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 651 668 695
Least Squares Mean (Standard Error)
Unit of Measure: millimeter
Change in Medial JSW at Week 56 Number Analyzed 486 participants 506 participants 523 participants
-0.25  (0.03) -0.34  (0.03) -0.19  (0.03)
Change in Medial JSW at Week 80 Number Analyzed 402 participants 413 participants 432 participants
-0.33  (0.04) -0.37  (0.04) -0.25  (0.03)
Change in Lateral JSW at Week 56 Number Analyzed 110 participants 94 participants 114 participants
-0.26  (0.07) -0.32  (0.07) -0.27  (0.07)
Change in Lateral JSW at Week 80 Number Analyzed 88 participants 75 participants 98 participants
-0.46  (0.08) -0.32  (0.09) -0.37  (0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change in medial JSW width at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0979
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.15 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change in medial JSW at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.24 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change in medial JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1162
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.17 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change in medial JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0128
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.22 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change in lateral JSW at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8885
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.17 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change in lateral JSW at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6345
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.24 to 0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change in lateral JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4406
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.32 to 0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change in lateral JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7109
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.19 to 0.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Joint Space Width of the Index Hip (Kellgren-Lawrence Grade 2 or 3) at Weeks 56 and 80
Hide Description Change from baseline in JSW was defined as narrowing in JSW compared to baseline in participants with Kellgren-Lawrence grade 2 or 3 over the course of the study. It was measured radiographically in the index hip in participants with OA. Kellgren-Lawrence grade system was a method of classifying the severity of hip OA using five grades i.e. 0 (no radiographic features of OA), 1 (doubtful JSN and possible osteophytic lipping), 2 (definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph), 3 (multiple osteophytes, definite JSN, sclerosis, possible bony deformity), 4 (large osteophytes, marked JSN, severe sclerosis and definite bony deformity). Higher grade indicating worse hip function.
Time Frame Baseline, Weeks 56 and 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 123 132 120
Least Squares Mean (Standard Error)
Unit of Measure: millimeter
Change at Week 56 Number Analyzed 110 participants 112 participants 107 participants
-0.35  (0.06) -0.40  (0.06) -0.21  (0.06)
Change at Week 80 Number Analyzed 89 participants 89 participants 86 participants
-0.46  (0.07) -0.35  (0.07) -0.28  (0.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.30 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0230
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.35 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0645
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.37 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.26 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Progression of Osteoarthritis in the Index Knee (Kellgren-Lawrence Grade 2 or 3) According to Bland and Altman Method at Weeks 56 and 80
Hide Description Progression of OA according to Bland-Altman as defined by a decrease JSW >=1.96 times within-participant standard deviation of change in JSW. The number of participants with progression of OA in the index knee are summarized separately by the compartment of OA at baseline (medial or lateral). Kellgren-Lawrence grade system was a method of classifying the severity of knee OA using five grades i.e. 0 [no radiographic features of OA], 1 [doubtful joint space narrowing (JSN) and possible osteophytic lipping], 2 [definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph], 3 [multiple osteophytes, definite JSN, sclerosis, possible bony deformity], 4 [large osteophytes, marked JSN, severe sclerosis and definite bony deformity]. Higher grade indicating worse knee function.
Time Frame Weeks 56 and 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 651 668 695
Measure Type: Count of Participants
Unit of Measure: Participants
Decreased medial JSW at Week 56 Number Analyzed 486 participants 506 participants 523 participants
33
   6.8%
43
   8.5%
20
   3.8%
Decreased medial JSW at Week 80 Number Analyzed 402 participants 413 participants 432 participants
29
   7.2%
38
   9.2%
16
   3.7%
Decreased lateral JSW at Week 56 Number Analyzed 110 participants 94 participants 114 participants
5
   4.5%
8
   8.5%
9
   7.9%
Decreased lateral JSW at Week 80 Number Analyzed 88 participants 75 participants 98 participants
9
  10.2%
4
   5.3%
7
   7.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Decrease in medial JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0358
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.85
Confidence Interval (2-Sided) 95%
1.04 to 3.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Decrease in medial JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.37
Confidence Interval (2-Sided) 95%
1.37 to 4.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Decrease in medial JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0301
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
1.07 to 3.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Decrease in medial JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.65
Confidence Interval (2-Sided) 95%
1.45 to 4.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Decrease in lateral JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3002
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.18 to 1.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Decrease in lateral JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8997
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.39 to 2.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Decrease in lateral JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4559
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.48
Confidence Interval (2-Sided) 95%
0.53 to 4.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Decrease in lateral JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5996
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.20 to 2.54
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Number of Participants With Progression of Osteoarthritis in the Index Hip (Kellgren-Lawrence Grade 2 or 3) According to Bland and Altman Method at Weeks 56 and 80
Hide Description Progression of OA according to Bland-Altman methodology as defined by a decrease in JSW >=1.96 times within-participant standard deviation of the change in JSW in the index hip. The number of participants with progression of OA in the index hip per Bland-Altman methodology are reported. Kellgren-Lawrence grade system was a method of classifying the severity of hip OA using five grades i.e. 0 (no radiographic features of OA), 1 (doubtful JSN and possible osteophytic lipping), 2 (definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph), 3 (multiple osteophytes, definite JSN, sclerosis, possible bony deformity), 4 (large osteophytes, marked JSN, severe sclerosis and definite bony deformity). Higher grade indicating worse hip function.
Time Frame Weeks 56 and 80
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 123 132 120
Measure Type: Count of Participants
Unit of Measure: Participants
Week 56 Number Analyzed 110 participants 112 participants 107 participants
10
   9.1%
10
   8.9%
3
   2.8%
Week 80 Number Analyzed 89 participants 89 participants 86 participants
9
  10.1%
9
  10.1%
3
   3.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Decrease at Week 56: Logistic regression model included treatment, and baseline JSW as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0714
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.37
Confidence Interval (2-Sided) 95%
0.90 to 12.65
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Decrease at Week 56: Logistic regression model included treatment, and baseline JSW as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0681
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.42
Confidence Interval (2-Sided) 95%
0.91 to 12.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Decrease at Week 80: Logistic regression model included treatment, and baseline JSW as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0967
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.12
Confidence Interval (2-Sided) 95%
0.81 to 11.95
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Decrease at Week 80: Logistic regression model included treatment, and baseline JSW as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0976
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.11
Confidence Interval (2-Sided) 95%
0.81 to 11.90
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline in WOMAC Pain Subscale at Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Hide Description WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS, which may not be a whole (integer) number. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo).
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
Change at Week 2 -1.65  (0.08) -1.49  (0.08) -1.55  (0.08)
Change at Week 4 -2.25  (0.09) -2.29  (0.09) -1.98  (0.09)
Change at Week 8 -2.41  (0.10) -2.65  (0.10) -2.27  (0.10)
Change at Week 24 -2.73  (0.13) -2.86  (0.13) -2.67  (0.13)
Change at Week 32 -2.64  (0.13) -2.68  (0.13) -2.57  (0.13)
Change at Week 40 -2.56  (0.13) -2.57  (0.13) -2.52  (0.13)
Change at Week 48 -2.54  (0.13) -2.48  (0.13) -2.47  (0.13)
Change at Week 56 -2.44  (0.13) -2.37  (0.13) -2.42  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2212
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.27 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4557
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.10 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.45 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.50 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1273
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.33 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.57 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6349
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.31 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1339
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.44 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6237
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.33 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4224
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.37 to 0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7526
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.31 to 0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7328
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.31 to 0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5888
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.33 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9345
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.28 to 0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8782
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.29 to 0.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7076
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.22 to 0.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline in WOMAC Pain Subscale at Week 64
Hide Description WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS, which may not be a whole (integer) number. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 1000 participants 995 participants 994 participants
7.01  (1.12) 7.02  (1.12) 6.96  (1.08)
Change at Week 64 Number Analyzed 437 participants 419 participants 445 participants
-3.47  (2.45) -3.12  (2.40) -3.85  (2.07)
18.Secondary Outcome
Title Change From Baseline in WOMAC Physical Function Subscale at Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Hide Description WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Time Frame Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo).
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Week 2 -1.76  (0.08) -1.64  (0.08) -1.55  (0.08)
Change at Week 4 -2.29  (0.09) -2.31  (0.09) -1.96  (0.09)
Change at Week 8 -2.46  (0.10) -2.69  (0.10) -2.27  (0.10)
Change at Week 24 -2.78  (0.13) -2.88  (0.13) -2.66  (0.13)
Change at Week 32 -2.66  (0.13) -2.67  (0.13) -2.55  (0.13)
Change at Week 40 -2.56  (0.13) -2.57  (0.13) -2.50  (0.13)
Change at Week 48 -2.56  (0.14) -2.49  (0.13) -2.45  (0.13)
Change at Week 56 -2.45  (0.14) -2.36  (0.13) -2.41  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0150
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.37 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3286
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.25 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.50 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.53 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0517
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.37 to 0.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.61 to -0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3621
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.37 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0832
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.47 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4072
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.38 to 0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3404
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.39 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6344
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.34 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5756
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.35 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4394
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.38 to 0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7747
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.31 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7305
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.32 to 0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7330
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.22 to 0.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in WOMAC Physical Function Subscale at Week 64
Hide Description WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 1000 participants 995 participants 994 participants
7.09  (1.07) 7.08  (1.11) 6.99  (1.09)
Change at Week 64 Number Analyzed 437 participants 419 participants 445 participants
-3.42  (2.40) -3.12  (2.41) -3.81  (2.12)
20.Secondary Outcome
Title Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Hide Description PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using IRT, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Time Frame Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).
Arm/Group Title Tanezumab 2.5 mg Tanezumab 5 mg NSAID
Hide Arm/Group Description:
Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.
Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Overall Number of Participants Analyzed 1002 998 996
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Week 2 -0.67  (0.03) -0.67  (0.03) -0.63  (0.03)
Change at Week 4 -0.81  (0.03) -0.84  (0.03) -0.69  (0.03)
Change at Week 8 -0.77  (0.03) -0.85  (0.03) -0.76  (0.03)
Change at Week 24 -0.74  (0.05) -0.79  (0.05) -0.74  (0.05)
Change at Week 32 -0.72  (0.05) -0.71  (0.05) -0.72  (0.05)
Change at Week 40 -0.70  (0.05) -0.69  (0.05) -0.69  (0.05)
Change at Week 48 -0.70  (0.05) -0.66  (0.05) -0.67  (0.05)
Change at Week 56 -0.65  (0.05) -0.60  (0.05) -0.66  (0.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2159
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.10 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2049
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.10 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.19 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tanezumab 5 mg, NSAID
Comments Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.21 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tanezumab 2.5 mg, NSAID
Comments Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis