Single Ascending Dose Study of Safety and Tolerability of Sarilumab and Methotrexate in Japanese Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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Primary Objective: To assess the safety and tolerability of a single dose of subcutaneously administered sarilumab in Japanese patients with rheumatoid arthritis (RA) who are receiving concomitant treatment with methotrexate. Secondary Objective: To assess the pharmacokinetic profile of a single subcutaneous (SC) dose of sarilumab in Japanese RA patients.

Detailed Description
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Total study duration per patient is up to 88 days Screening: 3 to 28 days Treatment: 1 day Follow-up: 57± 3 days after dosing

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety and Tolerability of Subcutaneously Administered Sarilumab in Japanese Patients With Rheumatoid Arthritis Receiving Concomitant Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: sarilumab SAR153191 (REGN88)
* Drug: placebo
* Drug: methotrexate
* Drug: folic acid


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female Japanese who are 20 to 65 years of age Diagnosis of rheumatoid arthritis (RA) ≥ 3 months duration Treated for a minimum of 8 weeks with Methotrexate (MTX) and with a stable dose of MTX (6-16 mg/week) for a minimum of 4 weeks prior to the screening visit Exclusion criteria: Autoimmune or inflammatory systemic or localized joint disease other than RA Women of a positive pregnancy test Latent or active tuberculosis Prior treatment with anti-interleukin-6 (anti-IL-6) or anti-interleukin-6 receptor (IL-6R) antagonist Treatment with anti-TNF agents, as follows: Etanercept: within 28 days prior to randomization Infliximab, adalimumab, golimumab, certolizumab pegol: within 42 days prior to randomization Received any live, attenuated vaccine within 3 months prior to the randomization visit (eg, varicella-zoster, oral polio, rubella vaccines) Significant concomitant illness such as, but not limited to, cardiovascular, renal, neurological, endocrinological, gastrointestinal, hepato-biliary, metabolic, pulmonary or lymphatic disease that would adversely affect the patient's participation in the study. Received surgery within 4 weeks prior to the screening visit or planned surgery during the study History of a systemic hypersensitivity reaction The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Sarilumab (SAR153191, REGN88) Dose 1<br>First dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: methotrexate<br>* Pharmaceutical form:capsule Route of administration: oral<br>Drug: folic acid<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Sarilumab (SAR153191, REGN88) Dose 2<br>Second dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: methotrexate<br>* Pharmaceutical form:capsule Route of administration: oral<br>Drug: folic acid<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Sarilumab (SAR153191, REGN88) Dose 3<br>Third dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: methotrexate<br>* Pharmaceutical form:capsule Route of administration: oral<br>Drug: folic acid<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Sarilumab (SAR153191, REGN88) Dose 4<br>Fourth dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: methotrexate<br>* Pharmaceutical form:capsule Route of administration: oral<br>Drug: folic acid<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Placebo Comparator: Placebo Dose 5<br>Placebo to match Sarilumab (SAR153191, REGN88) in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy | Drug: placebo<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: methotrexate<br>* Pharmaceutical form:capsule Route of administration: oral<br>Drug: folic acid<br>* Pharmaceutical form:tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety parameters (adverse events, laboratory data, vital signs, and ECG) |  | Up to 88 days or end-of-study (EoS) | 
| Assessment of the occurrence of anti-sarilumab antibodies |  | Day 1, Day 15, Day 29, Day 57 | 
| Assessment of the titer of anti-sarilumab antibodies |  | Day 1, Day 15, Day 29, Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter - maximum concentration (Cmax) |  | At each visit, up to 88 days | 
| Assessment of PK parameter - area under curve (AUC) |  | At each visit, up to 88 days | 
| Assessment of PK parameter - time to maximum concentration (tmax) |  | At each visit, up to 88 days |