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Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis

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ClinicalTrials.gov Identifier: NCT01753076
Recruitment Status : Completed
First Posted : December 20, 2012
Results First Posted : April 19, 2017
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis
Interventions Drug: Ozanezumab
Drug: Placebo
Enrollment 304
Recruitment Details  
Pre-assignment Details A total of 304 participants were randomized (151 to placebo; 153 to ozanezumab 15 milligrams [mg]/kilogram [kg]), and 303 participants (151 placebo; 152 ozanezumab 15 mg /kg ) received at least one dose of investigational product (one of the participants who did not receive any study drug was re-randomized to ozanezumab).
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description Participants (par) received placebo once every 2 weeks by intravenous infusion up to Week 46. Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46.
Period Title: Overall Study
Started 151 152
Completed 110 106
Not Completed 41 46
Reason Not Completed
Adverse Event             17             18
Lack of Efficacy             3             1
Lost to Follow-up             2             1
Physician Decision             4             2
Withdrawal by Subject             14             24
Other-Reached Protocol-defined Stopping             1             0
Arm/Group Title Placebo Ozanezumab 15 mg/kg Total
Hide Arm/Group Description Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Total of all reporting groups
Overall Number of Baseline Participants 151 152 303
Hide Baseline Analysis Population Description
One participant who did not receive any study drug was excluded from the intent-to-treat (ITT) population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 151 participants 152 participants 303 participants
55.5  (11.04) 55.7  (10.40) 55.6  (10.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 152 participants 303 participants
Female
54
  35.8%
49
  32.2%
103
  34.0%
Male
97
  64.2%
103
  67.8%
200
  66.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 151 participants 152 participants 303 participants
African American/African Heritage 1 2 3
Asian - Central/South Asian Heritage 2 3 5
Asian - East Asian Heritage 3 8 11
Asian - Japanese Heritage 5 10 15
Asian - South East Asian Heritage 13 5 18
White - Arabic/North African Heritage 3 2 5
White - White/Caucasian/European Heritage 124 121 245
Mixed Race 0 1 1
1.Primary Outcome
Title Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival
Hide Description The joint rank score is a combined assessment of function and survival. Function is assessed using change from Baseline in the ALSFRS-R total score. To calculate joint rank scores, every participant was compared with all other participants in a pair wise manner and assigned a score of -1, 0 or 1 based on their relative outcomes. A subject's joint rank score is the sum of their scores across the pair wise comparisons. The . The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing. Lower scores of ALSFRS-R reflect greater impairment.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only on-treatment data (data within 21 days of the last dose) were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 151 152
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
15.0  (13.58) -14.9  (13.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.120
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -30.0
Confidence Interval (2-Sided) 95%
-67.9 to 7.9
Estimation Comments A negative mean difference means that the direction of effect is in favor of placebo.
2.Secondary Outcome
Title Change From Baseline in the ALSFRS-R Total Score at Week 48
Hide Description The rate of decline was estimated by the change from Baseline in ALSFRS-R. The monthly slope for the ALSFRS-R score (i.e., the monthly rate of decline) was calculated as change from Baseline in the ALSFRS-R score at the last visit for that treatment period divided by the study day at the last visit for that treatment period /30.4. The Week 0 (Visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only on-treatment data (data within 21 days of the last dose) were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 104 101
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-9.1  (0.64) -10.4  (0.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.1 to 0.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Rate of Decline Over Week 48 in the ALSFRS-R Total Score
Hide Description The rate of decline was estimated by the change from Baseline in ALSFRS-R. The monthly slope for the ALSFRS-R score (i.e., the monthly rate of decline) was calculated as change from Baseline in the ALSFRS-R score at the last visit for that treatment period divided by the study day at the last visit for that treatment period devided by 30.4. The Week 0 (Visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only on-treatment data (data within 21 days of the last dose) were analyzed..
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 149 150
Least Squares Mean (Standard Error)
Unit of Measure: change in scores on a scale per month
-0.84  (0.063) -0.96  (0.062)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.173
Comments [Not Specified]
Method Random coefficients analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.30 to 0.05
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Slow Vital Capacity (SVC) at Week 48
Hide Description SVC was measured by using a validated spirometer. Three SVC measurements were performed for each participant at each assessment provided the difference from the second trial (if arranged by the numerical value) was not greater than 10%. If the difference between the best and the next best (based on the largest numerical value) SVC value from the first three trials was greater than 10%, additional trials (up to 5 in total) could have been performed. The Week 0 (visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. A mixed-model repeated measures (MMRM) adjusted for treatment, visit, treatment by visit, Baseline SVC, Baseline SVC by visit, riluzole use. and country group was used for the analysis.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at indicated time points were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 96 98
Least Squares Mean (Standard Error)
Unit of Measure: Liters (L)
-0.899  (0.0804) -1.026  (0.0804)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.265
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.127
Confidence Interval (2-Sided) 95%
-0.351 to 0.097
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Muscle Strength as Measured by Hand Held Dynamometry (HHD) Score at Week 48
Hide Description The HHD is a device placed between the hand of the practitioner and the tested body part and provides a quantified measurement of muscle strength. Each muscle was tested twice, and both values were recorded. Additionally, a third trial could have been performed if the variability between the first two trials was greater than 15 % or if the rater thought that one of the first two trials was not valid. The Week 0 (Visit 2) value was considered to be the Baseline value. Percent change from Baseline for each muscle group was calculated as 100*(HHD score minus the Baseline score) divided by the Baseline score. The average percent change was the mean percent change across the muscle groups that were non-missing/non-zero at Baseline. MMRM adjusted for treatment, visit, treatment by visit, number of non-missing/non-zero muscle groups at Baseline, number of non-missing/non-zero muscle groups at Baseline by Visit, riluzole use, and country group was used for the analysis.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 99 95
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-34.7  (3.77) -42.9  (3.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.125
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.2
Confidence Interval (2-Sided) 95%
-18.7 to 2.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Clinical Global Impression-improvement Scale (CGI-I) Responders at Week 48
Hide Description The CGI-I scale is a single observer-rated item measuring global improvement relative to Baseline. The CGI-I score is rated on a 7-point scale, from 1 (very much improved) to 7 (very much worse). Participant status at Baseline was assessed using the Clinical Global Impression Severity scale (CGI-S), which is a 7-point scale (1: normal, not at all ill; 7: most extremely ill) used to rate the severity of the participant's illness. Participants achieving a score of 1-4 in the CGI-I at Week 48 were considered to be responders. A a logistic regression adjusted for CGI-S at Baseline, riluzole use, and world region was used for the analysis.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 101 97
Measure Type: Number
Unit of Measure: Participants
23 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.36 to 1.49
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Overall Survival at Week 48 and Week 60
Hide Description Overall survival is defined as the time from randomization to death or censoring at the time point of analysis, whichever comes first. Kaplan Meier estimates at Week 48 were evaluated at Day 344. A participant was considered to have completed if he/she was censored at Day 344. Kaplan Meier estimates at Week 60 were evaluated at Day 428. A participant was considered to have completed if he/she was censored at Day 428. Confidence intervals were estimated using the Brookmeyer Crowley method. Results are shown as the estimated percentage of participants alive at Weeks 48 and 60. Week 48: Only on-treatment data (data within 21 days of the last dose) were analyzed. Week 60: Including off treatment data (data after 21 days after the last dose) were analyzed.
Time Frame Week 48 and Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Outcome assessments conducted at Week 48 and Week 60.
Participants received ozanezumab 15 mg/kg once every 2 weeks by intravenous infusion up to Week 46. Outcome assessments conducted at Week 48 and Week 60.
Overall Number of Participants Analyzed 151 152
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 48
95.5
(92.0 to 99.0)
94.3
(90.4 to 98.1)
Week 60
87.4
(81.5 to 93.3)
85.4
(79.4 to 91.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.986
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.34 to 2.89
Estimation Comments Week 48
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.923
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.53 to 2.01
Estimation Comments Week 60
8.Secondary Outcome
Title Progression-free Survival at Week 48
Hide Description Progression-free survival at Week 48 is defined as the time from randomization to progression (decline of at least six points on the ALSFRS-R from Baseline) or death or censored at Week 48, whichever comes first. Kaplan Meier estimates at Week 48 were evaluated at Day 344. A participant was considered to have completed if he/she was censored at Day 344. Confidence intervals were estimated using the Brookmeyer Crowley method. Results are shown as the estimated percentage of participants alive and without disease progression at Week 48.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only on-treatment data (data within 21 days of the last dose) were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 151 152
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants surviving
30.8
(23.0 to 38.6)
28.5
(21.1 to 35.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.642
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.81 to 1.42
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in the EuroQol 5 Dimensions-5 Level Short Form (EQ-5D-5L) Utility Score at Week 48
Hide Description A utility score for each participant was calculated based on the value set for England. The Week 0 (Visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. EQ-5D-5L is a standardized, participant-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant’s health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). . For each of these dimensions, the participant self assigned a score: 1 (no problems); 2 (slight problems); 3 (moderate problems); 4 (severe problems); 5 (extreme problems).Minimum score on scale was 1 and maximum score was 5 for each dimension. A negative change from Baseline indicates improvement.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 103 102
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-0.234  (0.0207) -0.238  (0.0207)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.004
Confidence Interval (2-Sided) 95%
-0.062 to 0.053
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Total Score at Week 48
Hide Description The ALSAQ-40 is a disease specific health status assessment for individuals with ALS/motor neuron disease. The ALSAQ-40 is comprised of 40 questions measuring 5discrete dimensions of health status that are affected by the disease: physical mobility (10 items); activities of daily living and independence (10 items); eating and drinking (3 items); communication (7 items); emotional reactions (10 items). Participants were asked to indicate the frequency of each event by selecting one of five options (Likert scale: 0-4): never/rarely/sometimes/often/ always or cannot do at all. The total score (minimum possible score=0, maximum possible score=160) was calculated by adding the five domain scores. A low score indicates a better health state. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. A mixed-model repeated measures adjusted for treatment, Visit, Treatment by Visit, and Baseline ALSAQ-40 total score was used for the analysis.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with data available at the specified time points were analyzed
Arm/Group Title Placebo Ozanezumab 15 mg/kg
Hide Arm/Group Description:
Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Participants received ozanezumab 15 milligrams per kilogram (mg/kg) once every 2 weeks by intravenous infusion up to Week 46. Final outcome assessment conducted at Week 48.
Overall Number of Participants Analyzed 102 96
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
19.2  (1.47) 20.6  (1.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanezumab 15 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-2.8 to 5.5
Estimation Comments [Not Specified]
Time Frame Up to Week 64
Adverse Event Reporting Description AEs and SAEs were collected in members of the Safety Population, comprised of all participants in the treatment cohort who gave informed consent, were randomized, and received at least one dose of study medication.
 
Arm/Group Title Placebo Ozanezumab IV
Hide Arm/Group Description Participants received placebo once every 2 weeks by intravenous infusion up to Week 46. Participants received ozanezumab 15 mg/kg once every 2 weeks by intravenous infusion up to Week 46.
All-Cause Mortality
Placebo Ozanezumab IV
Affected / at Risk (%) Affected / at Risk (%)
Total   13/151 (8.61%)   18/152 (11.84%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Ozanezumab IV
Affected / at Risk (%) Affected / at Risk (%)
Total   46/151 (30.46%)   47/152 (30.92%) 
Blood and lymphatic system disorders     
Anaemia  1  0/151 (0.00%)  1/152 (0.66%) 
Cardiac disorders     
Myocardial infarction  1  3/151 (1.99%)  1/152 (0.66%) 
Cardiac arrest  1  0/151 (0.00%)  1/152 (0.66%) 
Coronary artery stenosis  1  1/151 (0.66%)  0/152 (0.00%) 
Stress cardiomyopathy  1  1/151 (0.66%)  0/152 (0.00%) 
Ear and labyrinth disorders     
Vertigo positional  1  1/151 (0.66%)  1/152 (0.66%) 
Vertigo  1  0/151 (0.00%)  1/152 (0.66%) 
Eye disorders     
Blindness unilateral  1  1/151 (0.66%)  0/152 (0.00%) 
Gastrointestinal disorders     
Dysphagia  1  2/151 (1.32%)  0/152 (0.00%) 
Constipation  1  1/151 (0.66%)  0/152 (0.00%) 
Ileus  1  1/151 (0.66%)  0/152 (0.00%) 
Oral disorder  1  1/151 (0.66%)  0/152 (0.00%) 
Salivary hypersecretion  1  0/151 (0.00%)  1/152 (0.66%) 
Subileus  1  1/151 (0.66%)  0/152 (0.00%) 
Vomiting  1  1/151 (0.66%)  0/152 (0.00%) 
General disorders     
Chest pain  1  0/151 (0.00%)  2/152 (1.32%) 
Catheter site pain  1  1/151 (0.66%)  0/152 (0.00%) 
Death  1  1/151 (0.66%)  0/152 (0.00%) 
Euthanasia  1  1/151 (0.66%)  0/152 (0.00%) 
Non-cardiac chest pain  1  0/151 (0.00%)  1/152 (0.66%) 
Pyrexia  1  1/151 (0.66%)  0/152 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/151 (0.00%)  1/152 (0.66%) 
Infections and infestations     
Pneumonia  1  2/151 (1.32%)  4/152 (2.63%) 
Lower respiratory tract infection  1  1/151 (0.66%)  1/152 (0.66%) 
Sepsis  1  1/151 (0.66%)  1/152 (0.66%) 
Appendicitis  1  0/151 (0.00%)  1/152 (0.66%) 
Bacteraemia  1  0/151 (0.00%)  1/152 (0.66%) 
Bronchitis  1  0/151 (0.00%)  1/152 (0.66%) 
Infection  1  0/151 (0.00%)  1/152 (0.66%) 
Lobar pneumonia  1  1/151 (0.66%)  0/152 (0.00%) 
Upper respiratory tract infection  1  0/151 (0.00%)  1/152 (0.66%) 
Urosepsis  1  1/151 (0.66%)  0/152 (0.00%) 
Injury, poisoning and procedural complications     
Facial bones fracture  1  2/151 (1.32%)  1/152 (0.66%) 
Head injury  1  2/151 (1.32%)  1/152 (0.66%) 
Fall  1  1/151 (0.66%)  1/152 (0.66%) 
Humerus fracture  1  1/151 (0.66%)  1/152 (0.66%) 
Ligament sprain  1  1/151 (0.66%)  1/152 (0.66%) 
Rib fracture  1  1/151 (0.66%)  1/152 (0.66%) 
Wound  1  1/151 (0.66%)  1/152 (0.66%) 
Contusion  1  1/151 (0.66%)  0/152 (0.00%) 
Eye penetration  1  1/151 (0.66%)  0/152 (0.00%) 
Face injury  1  1/151 (0.66%)  0/152 (0.00%) 
Jaw fracture  1  1/151 (0.66%)  0/152 (0.00%) 
Joint dislocation  1  0/151 (0.00%)  1/152 (0.66%) 
Laceration  1  1/151 (0.66%)  0/152 (0.00%) 
Multiple fractures  1  1/151 (0.66%)  0/152 (0.00%) 
Procedural complication  1  0/151 (0.00%)  1/152 (0.66%) 
Scapula fracture  1  0/151 (0.00%)  1/152 (0.66%) 
Skin abrasion  1  1/151 (0.66%)  0/152 (0.00%) 
Stoma site pain  1  1/151 (0.66%)  0/152 (0.00%) 
Stress fracture  1  0/151 (0.00%)  1/152 (0.66%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/151 (0.00%)  1/152 (0.66%) 
Dehydration  1  1/151 (0.66%)  0/152 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  0/151 (0.00%)  1/152 (0.66%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder neoplasm  1  0/151 (0.00%)  1/152 (0.66%) 
Bladder transitional cell carcinoma  1  0/151 (0.00%)  1/152 (0.66%) 
Prostate cancer  1  0/151 (0.00%)  1/152 (0.66%) 
Nervous system disorders     
Amyotrophic lateral sclerosis  1  2/151 (1.32%)  2/152 (1.32%) 
Cerebral haemorrhage  1  0/151 (0.00%)  1/152 (0.66%) 
Cerebrovascular accident  1  1/151 (0.66%)  0/152 (0.00%) 
Dyskinesia  1  0/151 (0.00%)  1/152 (0.66%) 
Motor neurone disease  1  1/151 (0.66%)  0/152 (0.00%) 
Paraesthesia  1  1/151 (0.66%)  0/152 (0.00%) 
Parosmia  1  1/151 (0.66%)  0/152 (0.00%) 
Subarachnoid haemorrhage  1  1/151 (0.66%)  0/152 (0.00%) 
Syncope  1  0/151 (0.00%)  1/152 (0.66%) 
Psychiatric disorders     
Suicidal ideation  1  0/151 (0.00%)  1/152 (0.66%) 
Suicide attempt  1  0/151 (0.00%)  1/152 (0.66%) 
Renal and urinary disorders     
Nephrolithiasis  1  0/151 (0.00%)  2/152 (1.32%) 
Urinary retention  1  2/151 (1.32%)  0/152 (0.00%) 
Calculus urinary  1  1/151 (0.66%)  0/152 (0.00%) 
Haematuria  1  0/151 (0.00%)  1/152 (0.66%) 
Renal colic  1  1/151 (0.66%)  0/152 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  7/151 (4.64%)  12/152 (7.89%) 
Pneumonia aspiration  1  4/151 (2.65%)  4/152 (2.63%) 
Dyspnoea  1  3/151 (1.99%)  4/152 (2.63%) 
Pulmonary embolism  1  3/151 (1.99%)  3/152 (1.97%) 
Acute respiratory failure  1  1/151 (0.66%)  3/152 (1.97%) 
Hypercapnia  1  1/151 (0.66%)  1/152 (0.66%) 
Respiratory distress  1  2/151 (1.32%)  0/152 (0.00%) 
Asphyxia  1  0/151 (0.00%)  1/152 (0.66%) 
Hypoxia  1  0/151 (0.00%)  1/152 (0.66%) 
Pleurisy  1  1/151 (0.66%)  0/152 (0.00%) 
Respiratory arrest  1  1/151 (0.66%)  0/152 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/151 (0.66%)  1/152 (0.66%) 
Thrombosis  1  2/151 (1.32%)  0/152 (0.00%) 
Haematoma  1  0/151 (0.00%)  1/152 (0.66%) 
Hypertension  1  1/151 (0.66%)  0/152 (0.00%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Ozanezumab IV
Affected / at Risk (%) Affected / at Risk (%)
Total   119/151 (78.81%)   120/152 (78.95%) 
Gastrointestinal disorders     
Diarrhoea  1  12/151 (7.95%)  25/152 (16.45%) 
Constipation  1  12/151 (7.95%)  23/152 (15.13%) 
Nausea  1  11/151 (7.28%)  14/152 (9.21%) 
Dyspepsia  1  4/151 (2.65%)  10/152 (6.58%) 
Vomiting  1  8/151 (5.30%)  5/152 (3.29%) 
General disorders     
Fatigue  1  13/151 (8.61%)  11/152 (7.24%) 
Oedema peripheral  1  12/151 (7.95%)  12/152 (7.89%) 
Peripheral swelling  1  7/151 (4.64%)  8/152 (5.26%) 
Infections and infestations     
Nasopharyngitis  1  32/151 (21.19%)  35/152 (23.03%) 
Urinary tract infection  1  10/151 (6.62%)  5/152 (3.29%) 
Bronchitis  1  8/151 (5.30%)  6/152 (3.95%) 
Injury, poisoning and procedural complications     
Fall  1  68/151 (45.03%)  56/152 (36.84%) 
Contusion  1  18/151 (11.92%)  11/152 (7.24%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  8/151 (5.30%)  13/152 (8.55%) 
Arthralgia  1  9/151 (5.96%)  11/152 (7.24%) 
Pain in extremity  1  7/151 (4.64%)  13/152 (8.55%) 
Musculoskeletal pain  1  6/151 (3.97%)  11/152 (7.24%) 
Nervous system disorders     
Headache  1  26/151 (17.22%)  29/152 (19.08%) 
Dizziness  1  14/151 (9.27%)  16/152 (10.53%) 
Psychiatric disorders     
Anxiety  1  9/151 (5.96%)  7/152 (4.61%) 
Depression  1  5/151 (3.31%)  11/152 (7.24%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  20/151 (13.25%)  17/152 (11.18%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  5/151 (3.31%)  8/152 (5.26%) 
Vascular disorders     
Haematoma  1  10/151 (6.62%)  5/152 (3.29%) 
Hypertension  1  8/151 (5.30%)  4/152 (2.63%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01753076     History of Changes
Other Study ID Numbers: 112264
First Submitted: December 17, 2012
First Posted: December 20, 2012
Results First Submitted: December 1, 2016
Results First Posted: April 19, 2017
Last Update Posted: December 21, 2017