An Evaluation of Sarilumab Plus Methotrexate Compared to Etanercept Plus Methotrexate in RA Patients Not Responding to Adalimumab Plus Methotrexate

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the treatment effect of sarilumab and methotrexate (MTX) compared to etanercept and MTX in participants with rheumatoid arthritis (RA) and an inadequate response to adalimumab and MTX by evaluation of the Disease Activity Score for 28 joints (DAS28). Secondary Objectives: To assess the signs and symptoms of RA in participants taking sarilumab in combination with MTX. To assess the quality of life of participants with RA taking sarilumab in combination with MTX. To assess the safety and tolerability of sarilumab in combination with MTX in participants with RA.

Detailed Description
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The maximum study duration per participant enrolled in the open label run-in phase and was eligible to enroll in the randomized phase of main study was 54 weeks: open label screening period of up to 4 weeks open-label treatment period of 16 weeks randomized screening period of 2 to 4 weeks randomized treatment post-treatment safety follow-up period of 6 weeks. The maximum study duration per participant enrolled only in the open label run-in phase and was not eligible to enroll in the randomized phase of main study was 26 weeks: open label screening period of up to 4 weeks open-label treatment period of 16 weeks open label treatment post-treatment safety follow-up period of 6 weeks. The maximum study duration per participant enrolled in the open label run-in phase and was eligible to enroll in the sarilumab sub-study was 82 weeks: open label screening period of up to 4 weeks open-label treatment period of 16 weeks screening period of 2 to 4 weeks sarilumab treatment period of 52 weeks sub-study post-treatment safety follow-up period of 6 weeks.

Official Title
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A Randomized, Controlled Study of Sarilumab and Methotrexate (MTX) Versus Etanercept and MTX in Patients With Rheumatoid Arthritis (RA) and an Inadequate Response to 4 Months of Treatment With Adalimumab and MTX

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Sarilumab
* Drug: Etanercept
* Drug: Methotrexate
* Drug: Placebo (for sarilumab)
* Drug: Placebo (for etanercept)
* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of RA >/= 3 months duration. Continuous treatment of MTX 10 - 25 mg/week (or per local labeling requirements if the dose range differs) for at least 12 weeks before screening visit and on a stable dose for 8 weeks before screening visit. Active disease defined as: at least 6/66 swollen and 8/68 tender joints and high sensitivity C-reactive protein > 10 mg/L. Exclusion criteria: Age < 18 years. Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks of the screening visit. Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, or a change in dosage within 4 weeks of the screening visit. Prior treatment with a tumor necrosis factor (TNF)-alpha inhibitor, or other biological disease modifying anti-rheumatoid drug (DMARD) or Janus Kinase inhibitor. New treatment with or dose-adjustment of on-going nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors within 4 weeks of the screening visit. Treatment with traditional oral DMARD /immunosuppressive agents other than MTX within 4 weeks or 12 weeks before the screening visit, depending on DMARD. The above information is 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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab Open Label run-in<br>Adalimumab 40 mg every 2 weeks (Q2W) for 16 weeks added to stable dose of MTX. | Drug: Methotrexate<br>* Dispensed according to local practice.<br>Drug: Adalimumab<br>* Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous<br>|
| Active Comparator: Etanercept + MTX (Randomized)<br>Etanercept 50 mg in combination with Placebo for sarilumab Q2W and etanercept 50 mg on alternating weeks for 24 weeks added to stable dose of MTX. | Drug: Etanercept<br>* Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous<br>* Other names: Enbrel;Drug: Methotrexate<br>* Dispensed according to local practice.<br>Drug: Placebo (for sarilumab)<br> <br> |
| Experimental: Sarilumab 150 mg + MTX (Randomized)<br>Sarilumab 150 mg in combination with placebo for etanercept Q2W and placebo for etanercept on alternating weeks for 24 weeks added to stable dose of MTX. | Drug: Sarilumab<br>* Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous<br>* Other names: REGN88;Drug: Methotrexate<br>* Dispensed according to local practice.<br>Drug: Placebo (for etanercept)<br> <br> |
| Experimental: Sarilumab 200 mg + MTX (Randomized)<br>Sarilumab 200 mg in combination with placebo for etanercept Q2W and placebo for etanercept on alternating weeks for 24 weeks added to stable dose of MTX. | Drug: Sarilumab<br>* Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous<br>* Other names: REGN88;Drug: Methotrexate<br>* Dispensed according to local practice.<br>Drug: Placebo (for etanercept)<br> <br> |
| Experimental: Sarilumab 150 mg + MTX Open Label Sub-study<br>Sarilumab 150 mg Q2W for 52 weeks added to stable dose of MTX. | Drug: Sarilumab<br>* Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous<br>* Other names: REGN88;Drug: Methotrexate<br>* Dispensed according to local practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Disease Activity Score for 28 Joints - C-Reactive Protein (DAS28-CRP) Score at Week 24 |  | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least 20% Improvement in American College of Rheumatology (ACR20), at Least 50% Improvement in ACR (ACR50) and at Least 70% Improvement in ACR (ACR70) Efficacy Response Rates at Week 12 and Week 24 |  | Week 12 and Week 24 | 
| Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 12 and Week 24 |  | Week 12 and Week 24 | 
| Change From Baseline in DAS28-CRP Score at Week 12 |  | Baseline, Week 12 |