Effect of SAR153191 (REGN88) With Methotrexate in Patients With Active Rheumatoid Arthritis Who Failed TNF-α Blockers

Study Overview
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Brief Summary
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Primary Objective: - To demonstrate that sarilumab (SAR153191/REGN88) on top of methotrexate (MTX) was superior in efficacy to placebo for the relief of signs and symptoms of rheumatoid arthritis (RA), in participants with active RA who had failed up to 2 tumor necrosis factor-alpha (TNF-α) antagonists. Secondary Objectives: To assess the safety of sarilumab; To document the pharmacokinetic profile of sarilumab.

Detailed Description
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The duration of the study period for each participant was approximately 22 weeks; including up to 4 weeks screening period, 12-week double-blind treatment period and 6-week safety follow-up period. Participants who completed the 12-week treatment period were offered enrollment in a separate long-term extension study (LTS11210/NCT01146652).

Official Title
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A Randomized, Double-blind, Parallel-group, Placebo- and Active Calibrator-controlled Study Assessing the Clinical Benefit of SAR153191 Subcutaneous (SC) on Top of MTX in Patients With Active RA Who Have Failed Previous TNF-α Antagonists

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Sarilumab
* Drug: Placebo
* Drug: Golimumab
* Drug: methotrexate (MTX)
* Drug: Folic/folinic acid


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of rheumatoid arthritis ≥6 months duration and American College of Rheumatology (ACR) Class I-III functional status at screening and baseline visits; Active disease defined as: At least 6 of 68 tender joints and 6 of 66 swollen joints at screening and baseline visits, and hs-C-Reactive Protein (hs-CRP) >10 g/L or Erythrocyte Sedimentation Rate (ESR) >28 mm/hr at screening visit; Continuous treatment with Methotrexate for at least 12 weeks and on stable dose (minimum 10 mg/week) for at least 6 weeks prior to the screening visit; Participant considered as Primary TNF-α blocker nonresponder. i.e.: Appropriate for previous TNF-α blocker therapy Lack of adequate clinical response after at least 3 months TNF-α blocker therapy with MTX or other synthetic disease modifying anti-rheumatic drug (DMARD) co-therapy. Exclusion criteria: Age <18 years or >75 years; Pregnant or breastfeeding woman or woman of childbearing potential, unwilling to utilize adequate contraception or not to become pregnant during the entire study; Fever (>38°C), or chronic, persistent, or recurring infection(s); History of demyelinating disease; Current underlying hepatobiliary disease. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 2 mL to match sarilumab once a week (qw) and 0.5 mL to match golimumab every 4 weeks (q4w) on top of MTX (15-25 mg) qw for 12 weeks. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: methotrexate (MTX)<br>* Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)<br>Drug: Folic/folinic acid<br>* Pharmaceutical form: tablet Route of administration: oral Folic/folinic acid continued according to local standard.<br>|
| Active Comparator: Golimumab 50 mg<br>Golimumab 50 mg q4w and placebo (matched to sarilumab) qw on top of MTX (15-25 mg) qw for 12 weeks. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Golimumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: Simponi®;Drug: methotrexate (MTX)<br>* Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)<br>Drug: Folic/folinic acid<br>* Pharmaceutical form: tablet Route of administration: oral Folic/folinic acid continued according to local standard.<br>|
| Experimental: Sarilumab 150 mg<br>Sarilumab 150 mg qw and placebo (matched to golimumab) q4w on top of MTX (15-25 mg) qw for 12 weeks. | Drug: Sarilumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: REGN88;Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: methotrexate (MTX)<br>* Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)<br>Drug: Folic/folinic acid<br>* Pharmaceutical form: tablet Route of administration: oral Folic/folinic acid continued according to local standard.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved at Least 20% Improvement in American College of Rheumatology (ACR20) Core Set Disease Activity Index at Week 12 |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved at Least 50% Improvement in American College of Rheumatology (ACR50) Core Set Disease Activity Index at Week 12 |  | Week 12 | 
| Percentage of Participants Who Achieved at Least 70% Improvement in American College of Rheumatology Core (ACR70) Set Disease Activity Index at Week 12 |  | Week 12 | 
| Disease Activity Score for 28 Joints (DAS28) at Week 12 |  | Week 12 | 
| European League Against Rheumatism (EULAR) Response at Week 12 |  | Week 12 | 
| Percentage of Participants Achieving DAS28 Remission Score < 2.6 at Week 12 |  | Week 12 | 
| Pharmacokinetic (PK) Parameter: Serum Concentration of Functional and Bound Sarilumab |  | Week 12 |