Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01061736
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objectives:
Part A (dose ranging study):
To demonstrate that sarilumab (SAR153191/REGN88) on top of MTX was effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks.
Part B (pivotal study):
To demonstrate that sarilumab added to MTX was effective in:
* reduction of signs and symptoms of rheumatoid arthritis at 24 weeks
* inhibition of progression of structural damage at 52 weeks
* improvement in physical function at 16 weeks
Secondary Objectives:
Part B:
To demonstrate that sarilumab added to MTX was effective in induction of a major clinical response at 52 weeks
To assess the safety of sarilumab added to MTX
To document the pharmacokinetic profile of sarilumab added to MTX in participants with active rheumatoid arthritis who were inadequate responders to MTX therapy.
- Detailed Description
The total study duration for a participant was 16-22 weeks (Part A) and 56-62 weeks (Part B) broken down as follows:
* Screening: Up to 4 weeks
* Treatment: 12 weeks (Part A) and 52 weeks (Part B)\*
* Follow-up: 6 weeks (for participants who would not continue in the long-term extension study).
'\*' Participants successfully completing their treatment period would be offered the opportunity to enter the long term extension study LTS11210 (SARIL-RA-EXTEND) (NCT01146652).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1675
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Sarilumab Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part A: SAR 100 mg q2w Folic Acid Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: SAR 100 mg qw Folic Acid Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks. Part A: SAR 150 mg qw Folic Acid Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks. Part A: SAR 100 mg q2w Methotrexate Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: Placebo qw Folic Acid Placebo (for sarilumab) qw on top of MTX for 12 weeks. Part B Cohort 1: Non-selected Doses Sarilumab Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part A: SAR 150 mg q2w Sarilumab Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 150 mg q2w Placebo (for sarilumab) Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 100 mg q2w Sarilumab Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Methotrexate Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part B Cohort 1: Non-selected Doses Placebo (for sarilumab) Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part A: SAR 100 mg q2w Placebo (for sarilumab) Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: Placebo qw Placebo (for sarilumab) Placebo (for sarilumab) qw on top of MTX for 12 weeks. Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2) Placebo (for sarilumab) Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part A: SAR 150 mg q2w Methotrexate Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: Placebo qw Methotrexate Placebo (for sarilumab) qw on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Placebo (for sarilumab) Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2) Methotrexate Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part A: SAR 150 mg qw Methotrexate Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks. Part A: SAR 100 mg qw Sarilumab Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks. Part A: SAR 100 mg qw Methotrexate Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks. Part A: SAR 150 mg qw Sarilumab Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Sarilumab Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 150 mg q2w Folic Acid Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Folic Acid Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part B Cohort 1: Non-selected Doses Folic Acid Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part B Cohort 1: Non-selected Doses Methotrexate Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Methotrexate Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Folic Acid Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Methotrexate Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Sarilumab Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Folic Acid Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2) Folic Acid Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab.
- Primary Outcome Measures
Name Time Method Part A: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 Baseline to Week 12 ACR20 response was defined, based on guidelines set forth by the American College of Rheumatology (ACR), as ≥20 % improvement in tender joint count and swollen joint count as well as ≥20% improvement in at least 3 of 5 following measures: C-Reactive Protein (CRP), Participant assessment of pain; Participant's global assessment of disease activity; Physician global assessment of disease activity; and Health Assessment Question-Disability Index (HAQ-DI). Missing data imputed by Last Observation Carried Forward (LOCF).
Part B: Percentage of Participants Achieving ACR20 Response at Week 24 Baseline to Week 24 ACR20 improvement responses were determined without imputation of missing post-baseline values. In addition data collected after treatment discontinuation or rescue was set to missing. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.
Part B: Change From Baseline in Health Assessment Question Disability Index (HAQ-DI) at Week 16 Baseline, Week 16 HAQ-DI was a participant-reported questionnaire that assesses the difficulty of performing daily activities: dress/groom, arise, eat, walk, reach, grip, hygiene and common activities. Overall score range from 0=least difficulty to 3=extreme difficulty. An increase in the score indicates a worsening of physical function while a decrease in the score represents improvement. Data collected after treatment discontinuation was set to missing.
Part B: Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 52 Baseline, Week 52 The Sharp method modified by D. van der Heijde involves separate scores for erosions and joint space narrowing based on radiographs to assess the degree of structural damage. Total score range from 0 (normal) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Missing data were imputed by the linear extrapolation method.
- Secondary Outcome Measures
Name Time Method Part B: Percentage of Participants Achieving a Major Clinical Response at Week 52 Baseline up to Week 52 Major clinical response was defined as an ACR70 response maintained for at least 24 consecutive weeks. ACR70 response uses the same criteria as for ACR20 but requires 70% improvement. In the primary approach, data collected after treatment discontinuation or rescue was set to missing. No imputation of missing post-baseline values was performed. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.
Trial Locations
- Locations (262)
Investigational Site Number 840070
🇺🇸Anniston, Alabama, United States
Investigational Site Number 840004
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840072
🇺🇸Gilbert, Arizona, United States
Investigational Site Number 840029
🇺🇸Beverly Hills, California, United States
Investigational Site Number 840007
🇺🇸Palm Desert, California, United States
Investigational Site Number 840008
🇺🇸San Francisco, California, United States
Investigational Site Number 840021
🇺🇸Santa Maria, California, United States
Investigational Site Number 840049
🇺🇸Upland, California, United States
Investigational Site Number 840050
🇺🇸Dunedin, Florida, United States
Investigational Site Number 840041
🇺🇸Jacksonville, Florida, United States
Scroll for more (252 remaining)Investigational Site Number 840070🇺🇸Anniston, Alabama, United States