A Randomized, Double-blind, Multicenter Study With a Placebo-controlled Period Assessing the Efficacy and Safety of Sarilumab Added to Methotrexate (MTX) in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 243
- Locations
- 96
- Primary Endpoint
- Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 24
Study Overview
Brief Summary
Primary Objective:
-To demonstrate that sarilumab added to methotrexate (MTX) reduce signs and symptoms of rheumatoid arthritis (RA) in Japanese RA participants with an inadequate response to MTX.
Secondary Objective:
-To assess the safety of sarilumab added to MTX in Japanese RA participants with an inadequate response to MTX.
Detailed Description
The total duration of study was expected up to 62 weeks (screening period of 4 weeks, treatment period of 52 weeks, and a 6-week post treatment observation).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Sarilumab 150 mg/150 mg
Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (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 (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either tender joint count [TJC] or swollen joint count [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.
Intervention: Sarilumab SAR153191 (REGN88) (Drug)
Sarilumab 150 mg/150 mg
Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (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 (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either tender joint count [TJC] or swollen joint count [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.
Intervention: Methotrexate (Drug)
Sarilumab 150 mg/150 mg
Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (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 (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either tender joint count [TJC] or swollen joint count [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.
Intervention: Folic acid (Drug)
Sarilumab 200 mg/200 mg
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 (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.
Intervention: Sarilumab SAR153191 (REGN88) (Drug)
Sarilumab 200 mg/200 mg
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 (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.
Intervention: Methotrexate (Drug)
Sarilumab 200 mg/200 mg
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 (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.
Intervention: Folic acid (Drug)
Placebo/Sarilumab 150 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Sarilumab SAR153191 (REGN88) (Drug)
Placebo/Sarilumab 150 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Placebo (for sarilumab) (Other)
Placebo/Sarilumab 150 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Methotrexate (Drug)
Placebo/Sarilumab 150 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Folic acid (Drug)
Placebo/Sarilumab 200 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Sarilumab SAR153191 (REGN88) (Drug)
Placebo/Sarilumab 200 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Placebo (for sarilumab) (Other)
Placebo/Sarilumab 200 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Methotrexate (Drug)
Placebo/Sarilumab 200 mg
Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with 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.
Intervention: Folic acid (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 24
Time Frame: Week 24
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.
Secondary Outcomes
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters(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)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters(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)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes(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)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(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)
- Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities(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)
- Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities(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)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters(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)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters(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)