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A Study Assessing the Efficacy and Safety of Sarilumab Added to MTX in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis (SARIL-RA-KAKEHASI)

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ClinicalTrials.gov Identifier: NCT02293902
Recruitment Status : Completed
First Posted : November 19, 2014
Results First Posted : January 30, 2018
Last Update Posted : January 30, 2018
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 SAR153191 (REGN88)
Other: Placebo (for sarilumab)
Drug: Methotrexate
Drug: Folic acid
Enrollment 243
Recruitment Details The study was conducted at 95 centers in Japan between 06 November 2014 and 28 October 2016. A total of 388 participants were screened, of whom 243 participants were randomized and 145 were screen failures.
Pre-assignment Details Participants were randomized to receive sarilumab 150 mg, 200 mg or placebo in a double-blind period up to Week 24 followed by single-blind period during which participants originally given placebo were switched to sarilumab 150 mg or 200 mg; those originally given 150 mg, 200 mg in double-blind period, continued with same treatment up to Week 52.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg
Hide Arm/Group Description Placebo (for sarilumab) subcutaneous (SC) injection once every 2 weeks (q2w) in combination with methotrexate (MTX) and folic acid in double-blind period up to Week 24. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment. Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment. Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment. Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment. Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment.
Period Title: Double-Blind Period (Up to Week 24)
Started 82 81 80 0 0
Treated 81 81 80 0 0
Rescued [1] 44 6 8 0 0
Completed 71 [2] 74 [3] 70 [4] 0 0
Not Completed 11 7 10 0 0
Reason Not Completed
Adverse Event             5             6             8             0             0
Lack of Efficacy             5             1             2             0             0
Randomized but not Treated             1             0             0             0             0
[1]
Included both participants who completed and did not complete the study.
[2]
42 rescued and 29 not rescued completed.
[3]
6 rescued and 68 not rescued completed.
[4]
8 rescued and 62 not rescued completed.
Period Title: Single-Blind Period (Week 25 to Week 52)
Started 0 74 [1] 70 [2] 34 [3] 37 [4]
Completed 0 66 [5] 68 [6] 33 [7] 31 [8]
Not Completed 0 8 2 1 6
Reason Not Completed
Adverse Event             0             7             1             1             6
Lack of Efficacy             0             1             1             0             0
[1]
68 participants not rescued continued same treatment and 6 rescued continued open label treatment.
[2]
62 participants not rescued continued same treatment and 8 rescued continued open label treatment.
[3]
14 participants not rescued were switched and 20 rescued continued open label treatment.
[4]
15 participants not rescued were switched and 22 rescued continued open label treatment.
[5]
5 rescued and 61 not rescued completed.
[6]
8 rescued and 60 not rescued completed.
[7]
20 rescued and 13 not rescued completed.
[8]
18 rescued and 13 not rescued completed.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Total
Hide Arm/Group Description Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment. Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment . Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment . Total of all reporting groups
Overall Number of Baseline Participants 82 81 80 243
Hide Baseline Analysis Population Description
Analysis was performed on randomized population which included all participants who had been allocated to a randomized treatment regardless of whether the treatment was actually administered.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 82 participants 81 participants 80 participants 243 participants
53.4  (11.5) 56.1  (9.5) 55.3  (11.0) 54.9  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 81 participants 80 participants 243 participants
Female
65
  79.3%
63
  77.8%
61
  76.3%
189
  77.8%
Male
17
  20.7%
18
  22.2%
19
  23.8%
54
  22.2%
1.Primary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 24
Hide Description American College of Rheumatology (ACR) response is a composite rating scale that includes 7 variables: tender joints count (TJC [68 joints]); Swollen joints count (SJC [66 joints]); levels of an acute phase reactant (high sensitivity C-reactive protein [hs-CRP level]); participant’s assessment of pain (measured on 0 [no pain]-100 mm [worst pain] visual analog scale [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]). ACR20 response 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on modified intent-to-treat (mITT) population which included all randomized participants who received at least one dose of investigational medicinal product (IMP) and had an evaluable primary endpoint, irrespective of compliance with the study protocol and procedures.
Arm/Group Title Placebo Sarilumab 150 mg Sarilumab 200 mg
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24. Participants with inadequate response by Week 16 were rescued with open label sarilumab 200 mg q2w treatment.
Overall Number of Participants Analyzed 81 81 80
Measure Type: Number
Unit of Measure: percentage of participants
14.8 67.9 57.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 150 mg
Comments Analysis was performed using Cochran-Mantel-Haenszel (CMH) test stratified by prior biologic use (Yes, No) and weight at screening (<55 kg, >=55 kg).
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 12.185
Confidence Interval (2-Sided) 95%
5.583 to 26.594
Estimation Comments [Not Specified]
Other Statistical Analysis Placebo vs. Sarilumab 150 mg
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 200 mg
Comments Analysis was performed using CMH test stratified by prior biologic use (Yes, No) and weight at screening (<55 kg, >=55 kg).
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 7.227
Confidence Interval (2-Sided) 95%
3.446 to 15.158
Estimation Comments [Not Specified]
Other Statistical Analysis Placebo vs. Sarilumab 200 mg
2.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AEs that developed or worsened or became serious during double-blind on-treatment period, single-blind on-treatment period up to 6-week post-treatment follow-up period (up to Week 58) were considered treatment-emergent.
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population which included all randomized participants who actually received at least one dose or a partial dose of IMP.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
Treatment Emergent AEs 49 76 71 12 13 54
Treatment Emergent SAEs 6 8 5 0 2 4
3.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Hide Description

Criteria for potentially clinically significant vital sign abnormalities:

  • Systolic blood pressure supine (SBP[S]): <=95 mmHg and decrease from baseline (DFB) >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg
  • Diastolic blood pressure supine (DBP[S]): <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg
  • Orthostatic systolic blood pressure (SBP[O]): <=-20 mmHg
  • Orthostatic diastolic blood pressure (DBP[O]): <=-10 mmHg
  • Heart rate supine (HR[S]): <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm
  • Weight: >=5% DFB; >=5% IFB
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
SBP(S) <=95 mmHg and DFB >=20 mmHg Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
2 4 1 0 0 0
SBP(S) >=160 mmHg and IFB >=20 mmHg Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
2 5 5 0 1 8
DBP(S) <=45 mmHg and DFB >=10 mmHg Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
1 1 1 0 0 0
DBP(S)>=110 mmHg and IFB >=10 mmHg Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 1 0 0 0 0
SBP(O) <=-20 mmHg Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
8 21 23 2 2 12
DBP(O) <=-10 mmHg Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
8 17 12 0 1 10
HR(S) <=50 bpm and DFB >=20 bpm Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 4 1 0 0 1
HR(S) >=120 bpm and IFB >=20 bpm Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
1 0 0 0 0 0
Weight >=5% DFB Number Analyzed 80 participants 81 participants 80 participants 14 participants 14 participants 58 participants
5 5 7 0 0 4
Weight >=5% IFB Number Analyzed 80 participants 81 participants 80 participants 14 participants 14 participants 58 participants
5 31 27 7 6 15
4.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Hide Description

Criteria for potentially clinically significant ECG abnormalities:

  • PR Interval: >200 millisecond (ms); >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%
  • QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%
  • QT Interval: >500 ms
  • QTc Bazett (QTc B): >450 ms; 480 ms; 500 ms; IFB >30 and <=60 ms; IFB >60 ms
  • QTc Fridericia (QTc F): >450 ms; 480 ms; 500 ms; IFB >30 and <=60 ms; IFB >60 ms
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
PR Interval >200 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
6 9 5 0 2 6
PR Interval >200 ms and IFB >=25% Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 1 0 0 0 0
PR Interval >220 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
3 4 2 0 1 2
PR Interval >220 ms and IFB >=25% Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 1 0 0 0 0
PR Interval >240 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
2 1 0 0 1 2
PR Interval >240 ms and IFB >=25% Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 0
QRS Interval >110 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
2 2 2 1 1 3
QRS Interval >110 ms and IFB >=25% Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 1
QRS Interval >120 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
2 2 1 1 1 2
QRS Interval >120 ms and IFB >=25% Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 1
QT Interval >500 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
1 0 1 0 0 3
QTc B >450 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
12 16 22 2 3 18
QTc B >480 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 2 2 0 1 2
QTc B >500 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 0
QTc B IFB >30 and <=60 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
2 2 2 0 1 5
QTc B IFB >60 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 0
QTc F>450 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
7 11 14 0 2 12
QTc F>480 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 1 1
QTc F>500 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 0
QTc F IFB >30 and <=60 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
4 4 3 0 1 3
QTc F IFB >60 ms Number Analyzed 77 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 0
5.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters
Hide Description

Criteria for potentially clinically significant abnormalities:

  • Hemoglobin: <=115 g/L (Male[M]) or <=95 g/L (Female[F]); >=185 g/L (M) or >=165 g/L (F); DFB >=20 g/L
  • Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F); >=0.55 v/v (M) or >=0.5 v/v (F)
  • Red blood cells (RBC): >=6 Tera/L
  • Platelets: <50 Giga/L; >=50 and <100 Giga/L; >=700 Giga/L
  • White blood cells (WBC): <3.0 Giga/L (Non-Black[NB]) or <2.0 Giga/L (Black[B]); >=16.0 Giga/L
  • Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); <1.0 Giga/L
  • Lymphocytes: <0.5 Giga/L; >=0.5 Giga/L and < lower limit of normal (LLN); >4.0 Giga/L
  • Monocytes: >0.7 Giga/L
  • Basophils: >0.1 Giga/L
  • Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L)
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits (at least 4 weeks apart) in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
Hemoglobin <=115 g/L (M) or <=95 g/L (F) 9 4 5 0 1 5
Hemoglobin >=185 g/L (M) or >=165 g/L (F) 0 0 0 0 0 0
Hemoglobin DFB >=20 g/L 4 0 3 0 0 1
Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F) 17 10 14 0 3 6
Hematocrit >=0.55 v/v (M) or >=0.5 v/v (F) 0 0 0 0 0 0
RBC >=6 Tera/L 0 0 0 0 0 0
Platelets <50 Giga/L 0 1 0 0 0 0
Platelets >=50 and <100 Giga/L 0 2 4 0 0 1
Platelets >=700 Giga/L 1 0 0 0 0 0
WBC <3.0 Giga/L (NB) or <2.0 Giga/L (B) 0 30 23 5 6 17
WBC >=16.0 Giga/L 0 5 5 0 0 2
Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B) 0 31 24 5 6 18
Neutrophils <1.0 Giga/L 0 11 6 3 0 8
Lymphocytes <0.5 Giga/L 3 6 3 1 2 1
Lymphocytes >=0.5 Giga/L and <LLN 23 29 32 4 2 18
Lymphocytes >4.0 Giga/L 0 0 0 0 0 0
Monocytes >0.7 Giga/L 9 10 7 0 2 3
Basophils >0.1 Giga/L 6 11 9 1 0 9
Eosinophils>0.5 Giga/L or >ULN(if ULN>=0.5 Giga/L) 1 2 1 1 0 2
6.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters
Hide Description

Criteria for potentially clinically significant abnormalities:

  • Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L unfasted or >=7 mmol/L fasted
  • Hemoglobin A1c (HbA1c): >8%
  • Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L
  • LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L
  • Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits (at least 4 weeks apart) in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
Glucose <=3.9 mmol/L and <LLN Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 0 2 1 1 2
Glucose>=11.1 mmol/L unfasted or >=7 mmol/L fasted Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
3 8 4 0 0 1
HbA1c >8% Number Analyzed 79 participants 81 participants 78 participants 14 participants 15 participants 58 participants
0 0 0 0 0 0
Total cholesterol >=6.2 mmol/L Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
9 40 32 4 2 17
Total cholesterol >=7.74 mmol/L Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 7 5 0 1 3
LDL cholesterol >=4.1 mmol/L Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
3 20 17 3 1 7
LDL cholesterol >=4.9 mmol/L Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 4 6 0 1 2
Triglycerides >=4.6 mmol/L Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 0 3 0 1 2
Triglycerides >=5.6 mmol/L Number Analyzed 81 participants 81 participants 80 participants 14 participants 15 participants 58 participants
0 0 3 0 1 2
7.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes
Hide Description

Criteria for potentially clinically significant abnormalities:

  • Sodium: <=129 mmol/L; >=160 mmol/L
  • Potassium: <3 mmol/L; >=5.5 mmol/L
  • Chloride: <80 mmol/L; >115 mmol/L
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
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Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits (at least 4 weeks apart) in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
Sodium <=129 mmol/L 0 0 1 0 0 0
Sodium >=160 mmol/L 0 0 1 0 0 1
Potassium <3 mmol/L 0 0 1 0 0 0
Potassium >=5.5 mmol/L 0 0 2 0 1 0
Chloride <80 mmol/L 0 0 0 0 0 0
Chloride >115 mmol/L 0 0 0 0 0 1
8.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
Hide Description

Criteria for potentially clinically significant abnormalities:

  • Creatinine: >=150 micromol/L; >=30% change from baseline; >=100% change from baseline
  • Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to < 60 mL/min; >=60 to <90 mL/min
  • Blood urea nitrogen: >=17 mmol/L
  • Uric acid: <120 micromol/L; >408 micromol/L
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits (at least 4 weeks apart) in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
Creatinine >=150 micromol/L 0 1 1 0 1 0
Creatinine >=30% change from baseline 5 18 22 0 4 17
Creatinine >=100% change from baseline 0 1 1 0 1 0
Creatinine clearance <15 mL/min 0 0 0 0 0 0
Creatinine clearance >=15 to <30 mL/min 0 1 0 0 1 0
Creatinine clearance >=30 to <60 mL/min 6 12 14 0 2 7
Creatinine clearance >=60 to <90 mL/min 41 45 42 7 5 35
Blood urea nitrogen >=17 mmol/L 0 0 0 0 1 0
Uric acid <120 micromol/L 0 1 2 0 0 0
Uric acid >408 micromol/L 8 13 14 3 3 5
9.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Hide Description

Criteria for potentially clinically significant abnormalities:

  • Alanine Aminotransferase (ALT): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN
  • Aspartate aminotransferase (AST): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN
  • Alkaline phosphatase: >1.5 ULN
  • Total bilirubin (TBILI): >1.5 ULN; >2 ULN
  • Conjugated bilirubin (CBILI): >1.5 ULN; >2 ULN
  • Unconjugated bilirubin: >1.5 ULN; >2 ULN
  • ALT and TBILI: ALT >3 ULN and TBILI >2 ULN
  • CBILI and TBILI: CBILI >35% TBILI and TBILI >1.5 ULN
  • Albumin: <=25 g/L
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm : Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description:
Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24.
Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52.
Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits (at least 4 weeks apart) in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
Overall Number of Participants Analyzed 81 81 80 14 15 58
Measure Type: Number
Unit of Measure: participants
ALT >1 ULN and <=1.5 ULN 3 17 24 3 6 16
ALT >1.5 ULN and <=3 ULN 7 24 19 4 4 9
ALT >3 ULN and <=5 ULN 6 11 5 2 0 4
ALT >5 ULN and <=10 ULN 0 1 2 0 1 2
ALT >10 ULN and <=20 ULN 0 0 0 0 0 0
ALT >20 ULN 0 0 0 0 0 0
AST >1 ULN and <=1.5 ULN 7 34 32 6 8 22
AST >1.5 ULN and <=3 ULN 11 18 10 3 1 11
AST >3 ULN and <=5 ULN 1 5 2 1 1 3
AST >5 ULN and <=10 ULN 0 0 1 0 0 0
AST >10 ULN and <=20 ULN 0 0 0 0 0 0
AST >20 ULN 0 0 0 0 0 0
Alkaline phosphatase >1.5 ULN 0 2 0 0 0 0
TBILI >1.5 ULN 0 1 2 1 0 3
TBILI >2 ULN 0 0 1 0 0 1
CBILI >1.5 ULN 0 0 0 0 0 1
CBILI >2 ULN 0 0 0 0 0 1
Unconjugated bilirubin >1.5 ULN 0 0 1 0 0 1
Unconjugated bilirubin >2 ULN 0 0 0 0 0 0
ALT >3 ULN and TBILI >2 ULN 0 0 0 0 0 0
CBILI >35% TBILI and TBILI >1.5 0 0 0 0 0 1
Albumin <=25 g/L 0 0 0 0 0 0
Time Frame For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58.
Adverse Event Reporting Description Reported AEs are treatment-emergent AEs that is AEs that developed or worsened or became serious during double-blind on-treatment period, single-blind on-treatment period up to 6-week post-treatment follow-up period (up to Week 58).
 
Arm/Group Title Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Hide Arm/Group Description Placebo (for sarilumab) SC injection once q2w in combination with MTX and folic acid in double-blind period up to Week 24. Sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52. Participants who completed placebo (for sarilumab) treatment up to Week 24, were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in single-blind period up to Week 52. Participants who received either placebo or sarilumab 150 mg or 200 mg and had inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits (at least 4 weeks apart) in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment up to Week 52.
All-Cause Mortality
Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/81 (7.41%)   8/81 (9.88%)   5/80 (6.25%)   0/14 (0.00%)   2/15 (13.33%)   4/58 (6.90%) 
Blood and lymphatic system disorders             
Leukopenia  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/58 (1.72%) 
Neutropenia  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Cardiac disorders             
Acute myocardial infarction  1  1/81 (1.23%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Eye disorders             
Macular fibrosis  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Gastrointestinal disorders             
Chronic gastritis  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Infections and infestations             
Gastroenteritis  1  1/81 (1.23%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Gastroenteritis bacterial  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/58 (1.72%) 
Herpes zoster  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Infective myositis  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Pharyngeal abscess  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Pneumocystis jirovecii pneumonia  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Pneumonia pneumococcal  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/58 (1.72%) 
Sepsis  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Injury, poisoning and procedural complications             
Clavicle fracture  1  1/81 (1.23%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Radius fracture  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Musculoskeletal and connective tissue disorders             
Foot deformity  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Lumbar spinal stenosis  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Osteoporosis  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/58 (1.72%) 
Rheumatoid arthritis  1  2/81 (2.47%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Scoliosis  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Spinal column stenosis  1  1/81 (1.23%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Renal and urinary disorders             
Calculus urinary  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Organising pneumonia  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Pulmonary fibrosis  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  0/15 (0.00%)  0/58 (0.00%) 
Vascular disorders             
Venous thrombosis limb  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Sarilumab 150 mg/150 mg Sarilumab 200 mg/200 mg Placebo/Sarilumab 150 mg Placebo/Sarilumab 200 mg Sarilumab Rescue
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   35/81 (43.21%)   67/81 (82.72%)   59/80 (73.75%)   12/14 (85.71%)   13/15 (86.67%)   48/58 (82.76%) 
Blood and lymphatic system disorders             
Anaemia  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Leukopenia  1  0/81 (0.00%)  2/81 (2.47%)  1/80 (1.25%)  0/14 (0.00%)  2/15 (13.33%)  1/58 (1.72%) 
Neutropenia  1  0/81 (0.00%)  10/81 (12.35%)  9/80 (11.25%)  2/14 (14.29%)  1/15 (6.67%)  6/58 (10.34%) 
Eye disorders             
Blepharitis  1  1/81 (1.23%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Gastrointestinal disorders             
Anal erosion  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Anal fissure  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Dental caries  1  2/81 (2.47%)  2/81 (2.47%)  3/80 (3.75%)  1/14 (7.14%)  0/15 (0.00%)  2/58 (3.45%) 
Diarrhoea  1  0/81 (0.00%)  2/81 (2.47%)  2/80 (2.50%)  0/14 (0.00%)  2/15 (13.33%)  4/58 (6.90%) 
Gastric polyps  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Gastritis erosive  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Gastrooesophageal reflux disease  1  0/81 (0.00%)  0/81 (0.00%)  3/80 (3.75%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Lip erosion  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Mouth ulceration  1  1/81 (1.23%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Nausea  1  1/81 (1.23%)  0/81 (0.00%)  4/80 (5.00%)  0/14 (0.00%)  0/15 (0.00%)  5/58 (8.62%) 
Stomatitis  1  3/81 (3.70%)  6/81 (7.41%)  8/80 (10.00%)  2/14 (14.29%)  1/15 (6.67%)  7/58 (12.07%) 
General disorders             
Injection site erythema  1  0/81 (0.00%)  8/81 (9.88%)  7/80 (8.75%)  1/14 (7.14%)  0/15 (0.00%)  5/58 (8.62%) 
Injection site pruritus  1  0/81 (0.00%)  5/81 (6.17%)  4/80 (5.00%)  1/14 (7.14%)  0/15 (0.00%)  1/58 (1.72%) 
Hepatobiliary disorders             
Drug-induced liver injury  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Hepatic function abnormal  1  4/81 (4.94%)  8/81 (9.88%)  7/80 (8.75%)  0/14 (0.00%)  0/15 (0.00%)  4/58 (6.90%) 
Hepatic steatosis  1  0/81 (0.00%)  0/81 (0.00%)  2/80 (2.50%)  1/14 (7.14%)  1/15 (6.67%)  0/58 (0.00%) 
Infections and infestations             
Bronchitis  1  1/81 (1.23%)  4/81 (4.94%)  1/80 (1.25%)  0/14 (0.00%)  1/15 (6.67%)  1/58 (1.72%) 
Clostridium difficile colitis  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Cystitis  1  1/81 (1.23%)  5/81 (6.17%)  1/80 (1.25%)  0/14 (0.00%)  0/15 (0.00%)  1/58 (1.72%) 
Diarrhoea infectious  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Furuncle  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  1/58 (1.72%) 
Gastroenteritis  1  1/81 (1.23%)  2/81 (2.47%)  6/80 (7.50%)  0/14 (0.00%)  0/15 (0.00%)  3/58 (5.17%) 
Gingivitis  1  1/81 (1.23%)  2/81 (2.47%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  1/58 (1.72%) 
Influenza  1  1/81 (1.23%)  1/81 (1.23%)  2/80 (2.50%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Nasopharyngitis  1  12/81 (14.81%)  27/81 (33.33%)  23/80 (28.75%)  5/14 (35.71%)  4/15 (26.67%)  19/58 (32.76%) 
Oral candidiasis  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Oral herpes  1  2/81 (2.47%)  0/81 (0.00%)  2/80 (2.50%)  1/14 (7.14%)  1/15 (6.67%)  0/58 (0.00%) 
Otitis media  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Otitis media acute  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Periodontitis  1  0/81 (0.00%)  4/81 (4.94%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Pharyngitis  1  1/81 (1.23%)  4/81 (4.94%)  2/80 (2.50%)  0/14 (0.00%)  1/15 (6.67%)  3/58 (5.17%) 
Upper respiratory tract infection  1  4/81 (4.94%)  8/81 (9.88%)  7/80 (8.75%)  0/14 (0.00%)  0/15 (0.00%)  6/58 (10.34%) 
Injury, poisoning and procedural complications             
Arthropod bite  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  1/58 (1.72%) 
Arthropod sting  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Contusion  1  0/81 (0.00%)  2/81 (2.47%)  1/80 (1.25%)  1/14 (7.14%)  0/15 (0.00%)  2/58 (3.45%) 
Rib fracture  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Investigations             
Alanine aminotransferase increased  1  4/81 (4.94%)  7/81 (8.64%)  4/80 (5.00%)  3/14 (21.43%)  0/15 (0.00%)  3/58 (5.17%) 
Neutrophil count decreased  1  0/81 (0.00%)  2/81 (2.47%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  3/58 (5.17%) 
White blood cell count decreased  1  0/81 (0.00%)  4/81 (4.94%)  2/80 (2.50%)  0/14 (0.00%)  0/15 (0.00%)  4/58 (6.90%) 
Metabolism and nutrition disorders             
Hypercholesterolaemia  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Hyperkalaemia  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Back pain  1  0/81 (0.00%)  2/81 (2.47%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  2/58 (3.45%) 
Lumbar spinal stenosis  1  0/81 (0.00%)  1/81 (1.23%)  1/80 (1.25%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Musculoskeletal chest pain  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Musculoskeletal stiffness  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Osteoarthritis  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  1/14 (7.14%)  0/15 (0.00%)  0/58 (0.00%) 
Rheumatoid arthritis  1  2/81 (2.47%)  2/81 (2.47%)  4/80 (5.00%)  0/14 (0.00%)  1/15 (6.67%)  3/58 (5.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Lymphangioma  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Nervous system disorders             
Carpal tunnel syndrome  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Psychiatric disorders             
Delirium  1  0/81 (0.00%)  0/81 (0.00%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Renal and urinary disorders             
Renal impairment  1  0/81 (0.00%)  0/81 (0.00%)  1/80 (1.25%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Skin and subcutaneous tissue disorders             
Eczema  1  1/81 (1.23%)  7/81 (8.64%)  4/80 (5.00%)  1/14 (7.14%)  0/15 (0.00%)  3/58 (5.17%) 
Generalised erythema  1  0/81 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/58 (0.00%) 
Ingrowing nail  1  2/81 (2.47%)  2/81 (2.47%)  0/80 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  1/58 (1.72%) 
Vascular disorders             
Hypertension  1  0/81 (0.00%)  4/81 (4.94%)  5/80 (6.25%)  0/14 (0.00%)  0/15 (0.00%)  5/58 (8.62%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02293902     History of Changes
Other Study ID Numbers: EFC14059
U1111-1155-7401 ( Other Identifier: UTN )
First Submitted: November 13, 2014
First Posted: November 19, 2014
Results First Submitted: October 23, 2017
Results First Posted: January 30, 2018
Last Update Posted: January 30, 2018