Single-dose Study to Describe the Safety of Sarilumab and Tocilizumab in Patients With Rheumatoid Arthritis

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To describe the safety and tolerability, including laboratory abnormalities following a single dose of sarilumab or tocilizumab administered subcutaneously (SC) as monotherapy in Japanese patients with rheumatoid arthritis (RA). Secondary Objectives: To describe the laboratory abnormalities (absolute neutrophil count [ANC], platelet counts, total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and liver function tests [LFTs]) following a single dose of sarilumab or tocilizumab administered SC as monotherapy in Japanese patients with RA. To describe the pharmacokinetics (PK) of sarilumab and tocilizumab.

Detailed Description
-----------------
Total study duration (per patient) is expected to be up to 71 days including screening (3 to 28 days before dosing).

Official Title
-----------------
An Open-label, Randomized, Parallel Group, Single-dose Study to Describe the Safety of IL-6 Receptor Blockade With Sarilumab or Tocilizumab Monotherapy in Japanese Patients With Rheumatoid Arthritis

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: sarilumab SAR153191 (REGN88)
* Drug: tocilizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Patients with rheumatoid arthritis (RA) as defined by the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria. ACR Class I-III functional status, based on the 1991 revised criteria. Exclusion criteria: Patients less than 20 years of age. Prior treatment with any biologic anti-interleukin-6 (anti-IL-6) or interleukin-6 receptor (IL-6R) antagonist. Any parenteral or intraarticular glucocorticoid injection within 4 weeks prior to randomization. Treatment with prednisone higher than 10 mg or equivalent per day, or change in dosage within 4 weeks prior to randomization. Treatment with disease-modifying antirheumatic drugs (DMARDs), immunosuppressive agents, tumor necrosis factor (TNF) antagonists or any other RA-directed biologic agents within a certain amount of time prior to randomization. Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the screening visit, whichever is longer. Active or suspected tuberculosis (TB) or at high risk of contracting TB. Fever, or chronic, persistent, or recurring infection(s) requiring active treatment. 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
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<br>Single subcutaneous (SC) dose of sarilumab | Drug: sarilumab SAR153191 (REGN88)<br>* Pharmaceutical form:solution Route of administration: Subcutaneous injection<br>|
| Active Comparator: Tocilizumab<br>Single SC dose of tocilizumab | Drug: tocilizumab<br>* Pharmaceutical form:solution Route of administration: Subcutaneous injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with adverse events |  | 6 weeks | 
| Percentage of patients with potentially clinically significant laboratory abnormalities |  | 6 weeks | 
| Change from baseline in laboratory parameters (hematology and biochemistry) |  | Baseline, Day 15 | 
| Weighted average of change from baseline in laboratory parameters (hematology and biochemistry) |  | Baseline, Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter: maximum concentration (Cmax) |  | Day 1 to Day 43 | 
| Assessment of PK parameter: time to Cmax (tmax) |  | Day 1 to Day 43 | 
| Assessment of PK parameter: area under the curve from zero time until the last measurable concentration (AUClast) |  | Day 1 to Day 43 | 
| Change from baseline in laboratory parameters (hematology and biochemistry) |  | Baseline, Day 29 and Day 43 | 
| Weighted average of change from baseline in laboratory parameters (hematology and biochemistry) |  | Baseline, Day 29 and Day 43 |