Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo (for sarilumab); Drug: Adalimumab; Drug: Sarilumab; Drug: Placebo (for adalimumab)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02332590

U1111-1160-6154 (Other Identifier)

EFC14092

2014-002541-22 (EudraCT Number)

Details and patient eligibility

About

Primary Objective:

To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) in participants with active rheumatoid arthritis (RA) who were either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders.

Secondary Objectives:

To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy in participants with active RA who were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders, with respect to:

• Reduction of signs and symptoms of RA.
• Improvement in quality of life assessed by participant reported outcome questionnaires.

Assessment of the safety and tolerability of sarilumab monotherapy (including immunogenicity) throughout the study.

Full description

Total study duration was up to 310 weeks: Up to a 4 week screening period, 24 week randomized double-blind treatment phase, 276-week open-label extension, and 6 weeks post-treatment final study visit.

Enrollment: 369 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of RA greater than or equal to (>=)3 months duration.
• American College of Rheumatology (ACR) Class I-III functional status.
• Active RA was defined as:

At least 6 of 66 swollen joints and 8 of 68 tender joints, high sensitivity C-reactive protein (hs-CRP) >=8 mg/L or ESR >=28 millimeter per hour (mm/H), and DAS28-ESR greater than (>) 5.1.

• Participants as per Investigator judgment were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, or inadequate responders treated with an adequate MTX dose for at least 12 weeks.

Exclusion criteria

• Age <18 years or the legal age of consent in the country of the study site, whichever was higher.
• Current treatment with disease-modifying antirheumatic drug (DMARDs)/immunosuppressive agents including MTX, cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine or hydroxychloroquine within 2 weeks prior to the baseline (Randomization Visit) or azathioprine, cyclophosphamide within 12 weeks prior to baseline (Randomization Visit) or leflunomide within 8 weeks prior to the Randomization Visit, or 4 weeks after cholestyramine washout.
• Treatment with any prior biologic agent, including anti-interleukin 6 (IL-6), IL-6 receptor (IL-6R) antagonists, and prior treatment with a Janus kinase inhibitor.
• Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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369 participants in 2 patient groups

Adalimumab 40 mg/Sarilumab 200 mg

Active Comparator group

Description:

Adalimumab 40 milligrams (mg) subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during the double-blind (DB) period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (less than \[\<\] 20% improvement from baseline in tender joint count \[TJC\] and swollen joint count \[SJC\] for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in open label extension (OLE) period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).

Treatment:

Drug: Placebo (for sarilumab)

Drug: Adalimumab

Sarilumab 200 mg/Sarilumab 200 mg

Experimental group

Description:

Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (\<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).

Treatment:

Drug: Placebo (for adalimumab)

Drug: Sarilumab