To Evaluate the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Rheumatoid Arthritis (RA)

Study Overview
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Brief Summary
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Primary Objective: To evaluate the immunogenicity of sarilumab administered as monotherapy. Secondary Objectives: To evaluate the other safety aspects of sarilumab administered as monotherapy. To assess the exposure of sarilumab administered as monotherapy.

Detailed Description
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Total study duration was up to 34 weeks: Up to 4-week screening period, 24-week open-label treatment phase, 6-week post-treatment observation. After completion of the treatment phase of this study, participants were eligible to enter a long term safety study (LTS11210 - SARIL-RA-EXTEND) for continuous treatment with sarilumab (SAR153191 [REGN88]).

Official Title
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An Open-label, Randomized, Parallel Group Study Assessing the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: sarilumab SAR153191 (REGN88)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of rheumatoid arthritis (RA) ≥ 3 months. Moderately to severely active rheumatoid arthritis. Participants who per investigator judgment were incomplete responders to at least 12 weeks of an adequate dose of continuous treatment with or who were intolerant of one or a combination of non-biologic disease modifying anti-rheumatic drugs (DMARDs). Exclusion criteria: Participants < 18 years of age. Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA. History of juvenile idiopathic arthritis or arthritis onset prior to age 16. Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome. Prior treatment with any biologic anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies. Treatment with prednisone > 10 mg or equivalent per day, or change in dosage within 4 weeks prior to randomization. New treatment with or dose-adjustment of on-going nonsteroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors within 4 weeks prior to randomization, except for the use of low-dose acetylsalicylic acid for cardiovascular diseases. Use of parenteral glucocorticoids or intra-articular glucocorticoids injection within 4 weeks prior to randomization. Prior treatment with a Janus kinase (JAK) inhibitor (tofacitinib). New treatment or dose-adjustment to on-going medication for dyslipidemia, such as statin, within 6 weeks prior to randomization. Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first dose of study drug administration, whichever is longer. Participants with a history of malignancy other than adequately-treated carcinoma in-situ of the cervix, non-metastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization visit. Non-malignant lymphoproliferative disorders are also excluded. Participants with active tuberculosis or untreated latent tuberculosis infection. Pregnant or breast feeding women. 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sarilumab 150 mg q2w<br>Sarilumab 150 mg subcutaneous (SC) injection every two weeks (q2w) for 24 weeks. | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous<br>|
| Experimental: Sarilumab 200 mg q2w<br>Sarilumab 200 mg SC injection q2w for 24 weeks. | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | ADA to sarilumab and anti-sarilumab neutralizing antibodies in serum samples were determined using a validated electrochemiluminescence immunoassay method. Percentage of participants with positive ADA during treatment emergent adverse event (TEAE) period (time from first dose of investigational medicinal product [IMP] to last dose of IMP + 60 days) was determined. Persistent ADA Response: treatment-emergent ADA detected at 2 or more consecutive sampling time points during the TEAE period, where the first and last ADA positive samples were separated by a period of at least 16 weeks or if the last measured sample was positive. ADA samples were collected prior to IMP administration at Week 0 (baseline), Week 2, 4, 12, 24 and 30. | From Baseline to Week 30 [End of study (EOS)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Sarilumab Concentration | Trough Concentration (Ctrough). | Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, 24 and 30 |