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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: placebo; Drug: sarilumab SAR153191 (REGN88); Drug: methotrexate; Drug: folic acid

Detailed Description

Total study duration per patient is up to 88 days

1. Screening: 3 to 28 days
2. Treatment: 1 day
3. Follow-up: 57± 3 days after dosing

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Sendai-Shi, Japan
    • Investigational Site Number 392001
  • Sendai-Shi, Japan
    • Investigational Site Number 392002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Male or female Japanese who are 20 to 65 years of age
2. Diagnosis of rheumatoid arthritis (RA) ≥ 3 months duration
3. 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:

1. Autoimmune or inflammatory systemic or localized joint disease other than RA
2. Women of a positive pregnancy test
3. Latent or active tuberculosis
4. Prior treatment with anti-interleukin-6 (anti-IL-6) or anti-interleukin-6 receptor (IL-6R) antagonist

5. Treatment with anti-TNF agents, as follows:

   1. Etanercept: within 28 days prior to randomization
   2. Infliximab, adalimumab, golimumab, certolizumab pegol: within 42 days prior to randomization
6. Received any live, attenuated vaccine within 3 months prior to the randomization visit (eg, varicella-zoster, oral polio, rubella vaccines)
7. 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.
8. Received surgery within 4 weeks prior to the screening visit or planned surgery during the study
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sarilumab (SAR153191, REGN88) Dose 1; First dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form:solution Route of administration: subcutaneous; Drug: methotrexate; Pharmaceutical form:capsule Route of administration: oral; Drug: folic acid; Pharmaceutical form:tablet Route of administration: oral
Experimental: Sarilumab (SAR153191, REGN88) Dose 2; Second dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form:solution Route of administration: subcutaneous; Drug: methotrexate; Pharmaceutical form:capsule Route of administration: oral; Drug: folic acid; Pharmaceutical form:tablet Route of administration: oral
Experimental: Sarilumab (SAR153191, REGN88) Dose 3; Third dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form:solution Route of administration: subcutaneous; Drug: methotrexate; Pharmaceutical form:capsule Route of administration: oral; Drug: folic acid; Pharmaceutical form:tablet Route of administration: oral
Experimental: Sarilumab (SAR153191, REGN88) Dose 4; Fourth dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form:solution Route of administration: subcutaneous; Drug: methotrexate; Pharmaceutical form:capsule Route of administration: oral; Drug: folic acid; Pharmaceutical form:tablet Route of administration: oral
Placebo Comparator: Placebo Dose 5; Placebo to match Sarilumab (SAR153191, REGN88) in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy	Drug: placebo; Pharmaceutical form:solution Route of administration: subcutaneous; Drug: methotrexate; Pharmaceutical form:capsule Route of administration: oral; Drug: folic acid; Pharmaceutical form:tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: May 1, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (Estimate): May 9, 2013

Study Record Updates

• Last Update Posted (Estimate): January 28, 2014
• Last Update Submitted That Met QC Criteria: January 27, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Micronutrients; Vitamins; Reproductive Control Agents; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Folic Acid
• Other Study ID Numbers: TDU13402; U1111-1134-0048 (Other Identifier: UTN)