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Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)

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ClinicalTrials.gov Identifier: NCT02332590
Recruitment Status : Active, not recruiting
First Posted : January 7, 2015
Results First Posted : July 25, 2017
Last Update Posted : August 29, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Sarilumab
Drug: Adalimumab
Drug: Placebo (for sarilumab)
Drug: Placebo (for adalimumab)
Enrollment 369
Recruitment Details The study was conducted at 86 centers in 15 countries. A total of 540 participants were screened between 28 January 2015 and 09 July 2015, of whom 369 participants were randomized and 171 were screen failures. Screen failures were mainly due to exclusion criteria met and inclusion criteria not met.
Pre-assignment Details Participants were randomized in 1:1 ratio (Adalimumab 40 mg every 2 weeks [q2w]: Sarilumab 200 mg q2w) and treated for 24 weeks. Completers are those participants who completed 24 weeks randomized treatment.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks. Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Period Title: Overall Study
Started 185 184
Treated 184 184
Completed 156 [1] 165 [2]
Not Completed 29 19
Reason Not Completed
Adverse Event             15             11
Lack of Efficacy             4             2
Poor compliance to protocol             3             1
Randomized but not treated             1             0
Other than specified above             6             5
[1]
155 participants entered open-label treatment period and 1 did not enroll.
[2]
All 165 participants entered open-label treatment period.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg Total
Hide Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks. Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks. Total of all reporting groups
Overall Number of Baseline Participants 185 184 369
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 185 participants 184 participants 369 participants
53.6  (11.9) 50.9  (12.6) 52.2  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 185 participants 184 participants 369 participants
Female
150
  81.1%
157
  85.3%
307
  83.2%
Male
35
  18.9%
27
  14.7%
62
  16.8%
1.Primary Outcome
Title Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24
Hide Description DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the American College of Rheumatology (ACR) rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS); Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Least square (LS) mean and standard error (SE) at Week 24 were obtained using Mixed-effect model with repeated measures (MMRM) approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants. Number of participants analyzed = participants with DAS28-ESR assessment at both baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 165
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.20  (0.106) -3.28  (0.105)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline DAS28-ESR score as a continuous covariates. Hierarchical testing procedure was used to control overall alpha error rate at 0.05 level and handle multiple endpoint analyses. Testing was then performed sequentially in order endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.077
Confidence Interval (2-Sided) 95%
-1.361 to -0.793
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
2.Secondary Outcome
Title Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24
Hide Description DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants who discontinued treatment prior to Week 24 were analyzed as non-responders.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
7.0 26.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.879
Confidence Interval (2-Sided) 95%
2.536 to 9.389
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
3.Secondary Outcome
Title Percentage of Participants Achieving ACR50 Criteria at Week 24
Hide Description ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (C-reactive protein [CRP] level); participant’s assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant’s global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician’s global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant’s assessment of physical function (measured by Health Assessment Questionnaire - Disability Index [HAQ-DI], with scoring range of 0 [better health] - 3 [worst health]). ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. Participants were analyzed as non-responders from the time they discontinued treatment.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
29.7 45.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.976
Confidence Interval (2-Sided) 95%
1.289 to 3.028
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
4.Secondary Outcome
Title Percentage of Participants Achieving ACR70 Criteria at Week 24
Hide Description ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant’s assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant’s global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician’s global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant’s assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better health] - 3 [worst health]). ACR70 was defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments. Participants were analyzed as non-responders from the time they discontinued treatment.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
11.9 23.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0036
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.286
Confidence Interval (2-Sided) 95%
1.300 to 4.020
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
5.Secondary Outcome
Title Percentage of Participants Achieving ACR20 Criteria at Week 24
Hide Description ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant’s assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant’s global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician’s global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant’s assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better health] - 3 [worst health]). ACR20 was defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments. Participants were analyzed as non-responders from the time they discontinued treatment.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
58.4 71.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments Threshold for significance 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.800
Confidence Interval (2-Sided) 95%
1.168 to 2.773
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
6.Secondary Outcome
Title Change From Baseline in HAQ-DI at Week 24
Hide Description Physical function was assessed by HAQ-DI. It consisted of at least 2 or 3 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with HAQ-DI assessment at both baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 158 165
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.43  (0.045) -0.61  (0.045)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI score as a continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.182
Confidence Interval (2-Sided) 95%
-0.305 to -0.059
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
7.Secondary Outcome
Title Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24
Hide Description SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures health-related quality of life (HRQL) in the last 4 weeks covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 sub-scales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 4 sub-scales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a sub-scale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with SF-36 PCS score assessment at both baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 157 159
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.09  (0.555) 8.74  (0.555)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline SF-36 PCS score as a continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.650
Confidence Interval (2-Sided) 95%
1.147 to 4.153
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
8.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24
Hide Description The FACIT-F is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score range from 0 to 52, where higher score corresponds to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 by MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with FACIT-F score assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 158 165
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
8.41  (0.709) 10.18  (0.701)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg, Sarilumab 200 mg
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline FACIT-F score as a continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0689
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.768
Confidence Interval (2-Sided) 95%
-0.137 to 3.674
Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
9.Secondary Outcome
Title Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24
Hide Description SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures HRQL in the last 4 weeks covering 2 summary measures: PCS and MCS. PCS with 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with SF-36 - mental health component summary score assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 157 159
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.83  (0.774) 7.86  (0.773)
10.Secondary Outcome
Title Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24
Hide Description DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with DAS28-CRP score assessment at both baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 156 163
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.97  (0.094) -2.86  (0.093)
11.Secondary Outcome
Title Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24
Hide Description DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by hs-CRP in mg/L. The DAS28-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
13.5 34.2
12.Secondary Outcome
Title Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24
Hide Description DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.
Time Frame Week 24
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Hide Analysis Population Description
ITT Population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
14.1 42.9
13.Secondary Outcome
Title Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24
Hide Description CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant’s global disease activity (in cm), and physician’s global assessment (in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. Participants were analyzed as non-responders from the time they discontinued treatment.
Time Frame Week 24
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Hide Analysis Population Description
ITT population.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 185 184
Measure Type: Number
Unit of Measure: percentage of participants
2.7 7.1
14.Secondary Outcome
Title Change From Baseline in CDAI at Week 24
Hide Description CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant’s global disease activity (in cm), and physician’s global assessment of disease VAS (in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. LS means and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
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Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with CDAI assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 158 165
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-25.20  (0.842) -28.94  (0.834)
15.Secondary Outcome
Title Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24
Hide Description EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. EQ-5D specifically included to address concerns regarding the health economic impact of RA. EQ-5D-3L comprises of 5 questions on mobility, self-care, pain/discomfort, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems). The 5-dimensional 3-level systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-3L-VAS records the participant’s self-rated health on a vertical VAS that allows the participants to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
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ITT population. Number of participants analyzed = participants with EQ-5D-3L score assessment both at baseline and Week 24. Here, Number Analyzed = participants with available data for specified category for each arm, respectively.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 156 164
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
EQ-5D Single index utility score Number Analyzed 156 participants 160 participants
0.26  (0.019) 0.32  (0.019)
EQ-5D VAS Number Analyzed 156 participants 164 participants
19.94  (1.720) 24.22  (1.686)
16.Secondary Outcome
Title Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24
Hide Description RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well-being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Each NRS is assessed as a number between 0 and 10 that corresponds to the 7 domains. The values for each of these domains are weighed by participant assessment of relative importance and combined in a single and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
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ITT population. Number of participants analyzed = participants with RAID assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 157 161
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.30  (0.168) -3.08  (0.168)
17.Secondary Outcome
Title Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 60 70
Least Squares Mean (Standard Error)
Unit of Measure: days
0.05  (0.611) -0.28  (0.547)
18.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 60 70
Least Squares Mean (Standard Error)
Unit of Measure: days
-3.50  (0.525) -3.74  (0.456)
19.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 60 69
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.510  (0.3470) -2.919  (0.3073)
20.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 169
Least Squares Mean (Standard Error)
Unit of Measure: days
-4.22  (0.405) -5.49  (0.400)
21.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to Arthritis
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 169
Least Squares Mean (Standard Error)
Unit of Measure: days
-4.87  (0.451) -6.70  (0.445)
22.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 169
Least Squares Mean (Standard Error)
Unit of Measure: days
-3.33  (0.376) -4.14  (0.371)
23.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed =participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 168
Least Squares Mean (Standard Error)
Unit of Measure: days
-2.57  (0.401) -3.43  (0.398)
24.Secondary Outcome
Title Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
Hide Description The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 168
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.605  (0.2110) -3.276  (0.2099)
25.Secondary Outcome
Title Change From Baseline in Morning Stiffness VAS at Week 24
Hide Description RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with morning stiffness VAS assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 156 165
Least Squares Mean (Standard Error)
Unit of Measure: mm
-29.29  (1.970) -35.08  (1.947)
26.Secondary Outcome
Title Change From Baseline in Individual ACR Component - TJC and SJC at Week 24
Hide Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with TJC and SJC assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 158 166
Least Squares Mean (Standard Error)
Unit of Measure: joints
TJC -16.45  (0.781) -18.23  (0.772)
SJC -12.20  (0.450) -13.44  (0.444)
27.Secondary Outcome
Title Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24
Hide Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). Physician global VAS & participant global VAS was done on 100 mm horizontal anchored VAS, ranging from 0 “no arthritis activity” to 100 “maximal arthritis activity” and Pain VAS on 100 mm VAS, ranging from 0 “no pain” to 100 “worst pain”. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with individual ACR components assessment both at baseline and Week 24. Here, Number Analyzed = participants with available data for specified category for each arm, respectively.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 158 166
Least Squares Mean (Standard Error)
Unit of Measure: mm
Physician global VAS Number Analyzed 158 participants 166 participants
-37.80  (1.431) -45.33  (1.414)
Participant global VAS Number Analyzed 158 participants 165 participants
-24.82  (1.752) -33.30  (1.731)
Pain VAS Number Analyzed 157 participants 165 participants
-27.41  (1.802) -36.19  (1.776)
28.Secondary Outcome
Title Change From Baseline in Individual ACR Component - CRP Level at Week 24
Hide Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with CRP assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 156 164
Least Squares Mean (Standard Error)
Unit of Measure: mg/L
-2.91  (1.461) -17.01  (1.431)
29.Secondary Outcome
Title Change From Baseline in Individual ACR Component- ESR Level at Week 24
Hide Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). The ESR is a blood test that can reveal inflammatory activity. Inflammation can cause the cells to clump together. The farther the red blood cells have descended, the greater the inflammatory response. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with ESR assessment both at baseline and Week 24.
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description:
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Overall Number of Participants Analyzed 163 166
Least Squares Mean (Standard Error)
Unit of Measure: mm/hr
-12.74  (1.398) -32.11  (1.388)
30.Secondary Outcome
Title Sarilumab Exposure Assessed by Trough Serum Sarilumab Concentrations
Hide Description [Not Specified]
Time Frame Over time, maximum to Week 306
Outcome Measure Data Not Reported
31.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame Over time, maximum to Week 306
Outcome Measure Data Not Reported
32.Secondary Outcome
Title Clinically Significant Changes in Laboratory Values: Hematology, Clinical Chemistry, and Urinalysis
Hide Description [Not Specified]
Time Frame Over time, maximum to Week 306
Outcome Measure Data Not Reported
33.Secondary Outcome
Title Clinically Significant Changes in ECG
Hide Description [Not Specified]
Time Frame Over time, maximum to Week 306
Outcome Measure Data Not Reported
34.Secondary Outcome
Title Clinically Significant Changes in Vital Signs
Hide Description [Not Specified]
Time Frame Over time, maximum to Week 306
Outcome Measure Data Not Reported
35.Secondary Outcome
Title Measurement of Anti-Drug Antibody (ADA) Levels
Hide Description [Not Specified]
Time Frame Over time, maximum to Week 306
Outcome Measure Data Not Reported
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 24 regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description Reported AEs are treatment-emergent AEs developed/worsened during ‘on treatment period’ (time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized treatment and time from first dose of study drug up to last dose date of study drug + 60 days for participants who discontinued 24-week randomized treatment). Safety population consisted of all randomized participants who received ≥1 dose or part of a dose of study drug.
 
Arm/Group Title Adalimumab 40 mg Sarilumab 200 mg
Hide Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
All-Cause Mortality
Adalimumab 40 mg Sarilumab 200 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Adalimumab 40 mg Sarilumab 200 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   12/184 (6.52%)   9/184 (4.89%) 
Blood and lymphatic system disorders     
Neutropenia  1  0/184 (0.00%)  1/184 (0.54%) 
Cardiac disorders     
Cardiac failure acute  1  0/184 (0.00%)  1/184 (0.54%) 
Coronary artery dissection  1  0/184 (0.00%)  1/184 (0.54%) 
Papillary muscle rupture  1  0/184 (0.00%)  1/184 (0.54%) 
Gastrointestinal disorders     
Small intestinal obstruction  1  1/184 (0.54%)  0/184 (0.00%) 
Immune system disorders     
Serum sickness  1  1/184 (0.54%)  0/184 (0.00%) 
Infections and infestations     
Arthritis bacterial  1  1/184 (0.54%)  0/184 (0.00%) 
Bursitis infective  1  0/184 (0.00%)  1/184 (0.54%) 
Mastitis  1  0/184 (0.00%)  1/184 (0.54%) 
Respiratory tract infection  1  1/184 (0.54%)  0/184 (0.00%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/184 (0.00%)  1/184 (0.54%) 
Concussion  1  0/184 (0.00%)  1/184 (0.54%) 
Periorbital haematoma  1  0/184 (0.00%)  1/184 (0.54%) 
Wound  1  0/184 (0.00%)  1/184 (0.54%) 
Investigations     
Alanine aminotransferase increased  1  1/184 (0.54%)  0/184 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/184 (0.54%)  0/184 (0.00%) 
Back pain  1  0/184 (0.00%)  1/184 (0.54%) 
Intervertebral disc protrusion  1  0/184 (0.00%)  1/184 (0.54%) 
Lumbar spinal stenosis  1  1/184 (0.54%)  0/184 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/184 (0.54%)  0/184 (0.00%) 
Nervous system disorders     
Cerebral ischaemia  1  0/184 (0.00%)  1/184 (0.54%) 
Cerebrovascular accident  1  1/184 (0.54%)  0/184 (0.00%) 
Demyelinating polyneuropathy  1  0/184 (0.00%)  1/184 (0.54%) 
Multiple sclerosis  1  1/184 (0.54%)  0/184 (0.00%) 
Syncope  1  1/184 (0.54%)  0/184 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/184 (0.54%)  0/184 (0.00%) 
Vascular disorders     
Haematoma  1  0/184 (0.00%)  1/184 (0.54%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Adalimumab 40 mg Sarilumab 200 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   115/184 (62.50%)   116/184 (63.04%) 
Blood and lymphatic system disorders     
Anaemia  1  0/184 (0.00%)  2/184 (1.09%) 
Leukopenia  1  1/184 (0.54%)  1/184 (0.54%) 
Microcytic anaemia  1  1/184 (0.54%)  0/184 (0.00%) 
Neutropenia  1  1/184 (0.54%)  25/184 (13.59%) 
Cardiac disorders     
Atrial fibrillation  1  0/184 (0.00%)  2/184 (1.09%) 
Myocardial ischaemia  1  1/184 (0.54%)  0/184 (0.00%) 
Palpitations  1  2/184 (1.09%)  1/184 (0.54%) 
Congenital, familial and genetic disorders     
Vertebral artery hypoplasia  1  1/184 (0.54%)  0/184 (0.00%) 
Ear and labyrinth disorders     
Ear pain  1  0/184 (0.00%)  1/184 (0.54%) 
Middle ear inflammation  1  1/184 (0.54%)  0/184 (0.00%) 
Vertigo  1  2/184 (1.09%)  0/184 (0.00%) 
Eye disorders     
Blepharitis  1  0/184 (0.00%)  1/184 (0.54%) 
Cataract  1  0/184 (0.00%)  1/184 (0.54%) 
Conjunctival haemorrhage  1  0/184 (0.00%)  2/184 (1.09%) 
Diplopia  1  1/184 (0.54%)  0/184 (0.00%) 
Dry eye  1  0/184 (0.00%)  1/184 (0.54%) 
Ulcerative keratitis  1  0/184 (0.00%)  1/184 (0.54%) 
Uveitis  1  0/184 (0.00%)  1/184 (0.54%) 
Visual impairment  1  0/184 (0.00%)  1/184 (0.54%) 
Gastrointestinal disorders     
Abdominal pain  1  5/184 (2.72%)  0/184 (0.00%) 
Abdominal pain upper  1  1/184 (0.54%)  2/184 (1.09%) 
Aphthous ulcer  1  1/184 (0.54%)  1/184 (0.54%) 
Chronic gastritis  1  0/184 (0.00%)  1/184 (0.54%) 
Constipation  1  1/184 (0.54%)  0/184 (0.00%) 
Diarrhoea  1  5/184 (2.72%)  5/184 (2.72%) 
Dry mouth  1  0/184 (0.00%)  1/184 (0.54%) 
Dyspepsia  1  0/184 (0.00%)  1/184 (0.54%) 
Epigastric discomfort  1  0/184 (0.00%)  1/184 (0.54%) 
Gastric polyps  1  0/184 (0.00%)  1/184 (0.54%) 
Gastritis  1  1/184 (0.54%)  1/184 (0.54%) 
Gastrooesophageal reflux disease  1  0/184 (0.00%)  1/184 (0.54%) 
Inguinal hernia  1  1/184 (0.54%)  0/184 (0.00%) 
Mouth ulceration  1  0/184 (0.00%)  1/184 (0.54%) 
Nausea  1  0/184 (0.00%)  2/184 (1.09%) 
Oral mucosal exfoliation  1  1/184 (0.54%)  0/184 (0.00%) 
Sensitivity of teeth  1  0/184 (0.00%)  1/184 (0.54%) 
Toothache  1  0/184 (0.00%)  1/184 (0.54%) 
Vomiting  1  1/184 (0.54%)  2/184 (1.09%) 
General disorders     
Asthenia  1  1/184 (0.54%)  1/184 (0.54%) 
Fatigue  1  2/184 (1.09%)  2/184 (1.09%) 
Generalised oedema  1  1/184 (0.54%)  0/184 (0.00%) 
Injection site discolouration  1  0/184 (0.00%)  1/184 (0.54%) 
Injection site erythema  1  6/184 (3.26%)  14/184 (7.61%) 
Injection site haematoma  1  1/184 (0.54%)  0/184 (0.00%) 
Injection site oedema  1  1/184 (0.54%)  0/184 (0.00%) 
Injection site pain  1  0/184 (0.00%)  2/184 (1.09%) 
Injection site pruritus  1  0/184 (0.00%)  3/184 (1.63%) 
Injection site rash  1  1/184 (0.54%)  0/184 (0.00%) 
Injection site swelling  1  1/184 (0.54%)  3/184 (1.63%) 
Malaise  1  0/184 (0.00%)  1/184 (0.54%) 
Non-cardiac chest pain  1  2/184 (1.09%)  0/184 (0.00%) 
Oedema peripheral  1  2/184 (1.09%)  0/184 (0.00%) 
Peripheral swelling  1  0/184 (0.00%)  2/184 (1.09%) 
Pyrexia  1  1/184 (0.54%)  2/184 (1.09%) 
Hepatobiliary disorders     
Cholelithiasis  1  2/184 (1.09%)  0/184 (0.00%) 
Hepatic steatosis  1  0/184 (0.00%)  1/184 (0.54%) 
Immune system disorders     
Allergy to arthropod bite  1  1/184 (0.54%)  0/184 (0.00%) 
Hypersensitivity  1  0/184 (0.00%)  2/184 (1.09%) 
Infections and infestations     
Acute sinusitis  1  0/184 (0.00%)  1/184 (0.54%) 
Bronchitis  1  7/184 (3.80%)  12/184 (6.52%) 
Cellulitis  1  1/184 (0.54%)  1/184 (0.54%) 
Chronic sinusitis  1  1/184 (0.54%)  0/184 (0.00%) 
Conjunctivitis  1  1/184 (0.54%)  1/184 (0.54%) 
Cystitis  1  1/184 (0.54%)  1/184 (0.54%) 
Ear infection  1  1/184 (0.54%)  0/184 (0.00%) 
Erysipelas  1  0/184 (0.00%)  1/184 (0.54%) 
Fungal infection  1  0/184 (0.00%)  1/184 (0.54%) 
Fungal skin infection  1  0/184 (0.00%)  1/184 (0.54%) 
Furuncle  1  0/184 (0.00%)  1/184 (0.54%) 
Gastric infection  1  0/184 (0.00%)  1/184 (0.54%) 
Gastroenteritis  1  1/184 (0.54%)  1/184 (0.54%) 
Gastrointestinal viral infection  1  0/184 (0.00%)  1/184 (0.54%) 
Gingivitis  1  0/184 (0.00%)  1/184 (0.54%) 
Herpes dermatitis  1  0/184 (0.00%)  1/184 (0.54%) 
Herpes simplex  1  0/184 (0.00%)  1/184 (0.54%) 
Herpes zoster  1  0/184 (0.00%)  1/184 (0.54%) 
Hordeolum  1  1/184 (0.54%)  0/184 (0.00%) 
Influenza  1  2/184 (1.09%)  1/184 (0.54%) 
Laryngitis  1  0/184 (0.00%)  1/184 (0.54%) 
Nasopharyngitis  1  14/184 (7.61%)  11/184 (5.98%) 
Ophthalmic herpes zoster  1  1/184 (0.54%)  0/184 (0.00%) 
Oral candidiasis  1  1/184 (0.54%)  0/184 (0.00%) 
Oral fungal infection  1  1/184 (0.54%)  0/184 (0.00%) 
Oral herpes  1  1/184 (0.54%)  1/184 (0.54%) 
Paronychia  1  1/184 (0.54%)  1/184 (0.54%) 
Pharyngitis  1  5/184 (2.72%)  3/184 (1.63%) 
Pharyngitis streptococcal  1  1/184 (0.54%)  0/184 (0.00%) 
Pulmonary tuberculosis  1  1/184 (0.54%)  0/184 (0.00%) 
Respiratory tract infection viral  1  0/184 (0.00%)  1/184 (0.54%) 
Rhinitis  1  1/184 (0.54%)  2/184 (1.09%) 
Scrub typhus  1  1/184 (0.54%)  0/184 (0.00%) 
Sialoadenitis  1  0/184 (0.00%)  1/184 (0.54%) 
Sinusitis  1  0/184 (0.00%)  2/184 (1.09%) 
Subcutaneous abscess  1  1/184 (0.54%)  0/184 (0.00%) 
Tonsillitis  1  1/184 (0.54%)  1/184 (0.54%) 
Tonsillitis bacterial  1  1/184 (0.54%)  0/184 (0.00%) 
Tooth infection  1  1/184 (0.54%)  0/184 (0.00%) 
Tracheitis  1  0/184 (0.00%)  1/184 (0.54%) 
Upper respiratory tract infection  1  7/184 (3.80%)  3/184 (1.63%) 
Urinary tract infection  1  4/184 (2.17%)  5/184 (2.72%) 
Viral diarrhoea  1  1/184 (0.54%)  0/184 (0.00%) 
Viral upper respiratory tract infection  1  0/184 (0.00%)  1/184 (0.54%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  11/184 (5.98%)  5/184 (2.72%) 
Animal bite  1  0/184 (0.00%)  1/184 (0.54%) 
Contusion  1  2/184 (1.09%)  1/184 (0.54%) 
Fall  1  3/184 (1.63%)  1/184 (0.54%) 
Foot fracture  1  1/184 (0.54%)  0/184 (0.00%) 
Hand fracture  1  1/184 (0.54%)  0/184 (0.00%) 
Intentional overdose  1  1/184 (0.54%)  2/184 (1.09%) 
Ligament sprain  1  0/184 (0.00%)  1/184 (0.54%) 
Limb injury  1  0/184 (0.00%)  1/184 (0.54%) 
Muscle rupture  1  0/184 (0.00%)  1/184 (0.54%) 
Post-traumatic pain  1  1/184 (0.54%)  0/184 (0.00%) 
Scratch  1  1/184 (0.54%)  0/184 (0.00%) 
Skin abrasion  1  1/184 (0.54%)  0/184 (0.00%) 
Wound  1  1/184 (0.54%)  1/184 (0.54%) 
Investigations     
Activated partial thromboplastin time prolonged  1  1/184 (0.54%)  0/184 (0.00%) 
Alanine aminotransferase increased  1  6/184 (3.26%)  7/184 (3.80%) 
Aspartate aminotransferase increased  1  3/184 (1.63%)  1/184 (0.54%) 
Blood creatinine increased  1  0/184 (0.00%)  2/184 (1.09%) 
Blood lactate dehydrogenase increased  1  0/184 (0.00%)  1/184 (0.54%) 
Blood pressure increased  1  0/184 (0.00%)  1/184 (0.54%) 
Creatinine renal clearance decreased  1  0/184 (0.00%)  1/184 (0.54%) 
Electrocardiogram ST segment elevation  1  1/184 (0.54%)  0/184 (0.00%) 
Eosinophil count increased  1  0/184 (0.00%)  1/184 (0.54%) 
Haemoglobin decreased  1  1/184 (0.54%)  0/184 (0.00%) 
Hepatic enzyme increased  1  0/184 (0.00%)  1/184 (0.54%) 
Liver function test abnormal  1  1/184 (0.54%)  0/184 (0.00%) 
Neutrophil count decreased  1  1/184 (0.54%)  1/184 (0.54%) 
Transaminases increased  1  0/184 (0.00%)  1/184 (0.54%) 
Weight decreased  1  1/184 (0.54%)  0/184 (0.00%) 
White blood cell count decreased  1  0/184 (0.00%)  1/184 (0.54%) 
Metabolism and nutrition disorders     
Dyslipidaemia  1  3/184 (1.63%)  2/184 (1.09%) 
Glucose tolerance impaired  1  0/184 (0.00%)  1/184 (0.54%) 
Hypercholesterolaemia  1  2/184 (1.09%)  0/184 (0.00%) 
Hyperlipidaemia  1  2/184 (1.09%)  1/184 (0.54%) 
Hypertriglyceridaemia  1  1/184 (0.54%)  0/184 (0.00%) 
Impaired fasting glucose  1  1/184 (0.54%)  0/184 (0.00%) 
Type 2 diabetes mellitus  1  0/184 (0.00%)  1/184 (0.54%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/184 (1.63%)  5/184 (2.72%) 
Arthritis  1  0/184 (0.00%)  2/184 (1.09%) 
Back pain  1  3/184 (1.63%)  2/184 (1.09%) 
Bursitis  1  1/184 (0.54%)  0/184 (0.00%) 
Muscle spasms  1  0/184 (0.00%)  1/184 (0.54%) 
Musculoskeletal pain  1  2/184 (1.09%)  1/184 (0.54%) 
Musculoskeletal stiffness  1  1/184 (0.54%)  0/184 (0.00%) 
Myalgia  1  1/184 (0.54%)  1/184 (0.54%) 
Neck pain  1  2/184 (1.09%)  1/184 (0.54%) 
Osteoarthritis  1  1/184 (0.54%)  2/184 (1.09%) 
Osteoporotic fracture  1  1/184 (0.54%)  0/184 (0.00%) 
Pain in extremity  1  0/184 (0.00%)  2/184 (1.09%) 
Rheumatoid arthritis  1  7/184 (3.80%)  1/184 (0.54%) 
Spinal osteoarthritis  1  2/184 (1.09%)  0/184 (0.00%) 
Synovial cyst  1  1/184 (0.54%)  0/184 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Leiomyoma  1  0/184 (0.00%)  1/184 (0.54%) 
Uterine leiomyoma  1  1/184 (0.54%)  0/184 (0.00%) 
Nervous system disorders     
Carotid artery disease  1  0/184 (0.00%)  1/184 (0.54%) 
Dizziness  1  1/184 (0.54%)  2/184 (1.09%) 
Headache  1  12/184 (6.52%)  7/184 (3.80%) 
Migraine  1  1/184 (0.54%)  0/184 (0.00%) 
Paraesthesia  1  0/184 (0.00%)  1/184 (0.54%) 
Paresis  1  0/184 (0.00%)  1/184 (0.54%) 
Polyneuropathy  1  1/184 (0.54%)  0/184 (0.00%) 
Presyncope  1  0/184 (0.00%)  1/184 (0.54%) 
Radiculopathy  1  1/184 (0.54%)  0/184 (0.00%) 
Somnolence  1  1/184 (0.54%)  0/184 (0.00%) 
Vascular encephalopathy  1  1/184 (0.54%)  0/184 (0.00%) 
Psychiatric disorders     
Depression  1  1/184 (0.54%)  3/184 (1.63%) 
Grief reaction  1  1/184 (0.54%)  0/184 (0.00%) 
Insomnia  1  2/184 (1.09%)  3/184 (1.63%) 
Mental disorder  1  0/184 (0.00%)  1/184 (0.54%) 
Middle insomnia  1  1/184 (0.54%)  0/184 (0.00%) 
Panic attack  1  1/184 (0.54%)  0/184 (0.00%) 
Renal and urinary disorders     
Dysuria  1  0/184 (0.00%)  1/184 (0.54%) 
Renal colic  1  0/184 (0.00%)  1/184 (0.54%) 
Renal cyst  1  1/184 (0.54%)  0/184 (0.00%) 
Reproductive system and breast disorders     
Dysmenorrhoea  1  1/184 (0.54%)  1/184 (0.54%) 
Respiratory, thoracic and mediastinal disorders     
Bronchiectasis  1  1/184 (0.54%)  0/184 (0.00%) 
Dyspnoea  1  0/184 (0.00%)  1/184 (0.54%) 
Epistaxis  1  1/184 (0.54%)  0/184 (0.00%) 
Oropharyngeal pain  1  1/184 (0.54%)  2/184 (1.09%) 
Pulmonary fibrosis  1  1/184 (0.54%)  0/184 (0.00%) 
Rhinitis allergic  1  0/184 (0.00%)  1/184 (0.54%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  1/184 (0.54%)  1/184 (0.54%) 
Dermatitis allergic  1  2/184 (1.09%)  2/184 (1.09%) 
Dermatitis contact  1  0/184 (0.00%)  1/184 (0.54%) 
Hypersensitivity vasculitis  1  1/184 (0.54%)  0/184 (0.00%) 
Ingrowing nail  1  0/184 (0.00%)  1/184 (0.54%) 
Miliaria  1  0/184 (0.00%)  1/184 (0.54%) 
Photosensitivity reaction  1  1/184 (0.54%)  0/184 (0.00%) 
Pityriasis rosea  1  1/184 (0.54%)  0/184 (0.00%) 
Pruritus  1  1/184 (0.54%)  2/184 (1.09%) 
Pruritus allergic  1  1/184 (0.54%)  0/184 (0.00%) 
Pustular psoriasis  1  0/184 (0.00%)  1/184 (0.54%) 
Rash  1  3/184 (1.63%)  1/184 (0.54%) 
Rash papular  1  1/184 (0.54%)  0/184 (0.00%) 
Rash pruritic  1  0/184 (0.00%)  1/184 (0.54%) 
Seborrhoeic dermatitis  1  0/184 (0.00%)  1/184 (0.54%) 
Skin ulcer  1  1/184 (0.54%)  0/184 (0.00%) 
Solar dermatitis  1  0/184 (0.00%)  1/184 (0.54%) 
Urticaria  1  0/184 (0.00%)  1/184 (0.54%) 
Social circumstances     
Menopause  1  1/184 (0.54%)  0/184 (0.00%) 
Surgical and medical procedures     
Tooth repair  1  1/184 (0.54%)  0/184 (0.00%) 
Vascular disorders     
Aortic arteriosclerosis  1  1/184 (0.54%)  0/184 (0.00%) 
Arterial stenosis  1  0/184 (0.00%)  1/184 (0.54%) 
Brachiocephalic arteriosclerosis  1  1/184 (0.54%)  0/184 (0.00%) 
Deep vein thrombosis  1  0/184 (0.00%)  1/184 (0.54%) 
Hot flush  1  1/184 (0.54%)  1/184 (0.54%) 
Hypertension  1  4/184 (2.17%)  3/184 (1.63%) 
Vasculitis  1  0/184 (0.00%)  1/184 (0.54%) 
Venous thrombosis limb  1  1/184 (0.54%)  0/184 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
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Name/Title: Trial Transparency Team
Organization: Sanofi
EMail: Contact-US@sanofi.com
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02332590     History of Changes
Other Study ID Numbers: EFC14092
2014-002541-22 ( EudraCT Number )
U1111-1160-6154 ( Other Identifier: UTN )
First Submitted: January 5, 2015
First Posted: January 7, 2015
Results First Submitted: May 24, 2017
Results First Posted: July 25, 2017
Last Update Posted: August 29, 2019