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

Sanofi

Status and phase: Completed; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: methotrexate; Drug: placebo; Drug: folic acid; Drug: sarilumab SAR153191 (REGN88)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01850680

TDU13402

U1111-1134-0048 (Other Identifier)

Details and patient eligibility

About

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.

Full 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

Enrollment: 61 patients

Sex: All

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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61 participants in 5 patient groups, including a placebo group

Sarilumab (SAR153191, REGN88) Dose 1

Experimental group

Description:

First dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy

Treatment:

Drug: methotrexate

Drug: folic acid

Drug: sarilumab SAR153191 (REGN88)

Sarilumab (SAR153191, REGN88) Dose 2

Experimental group

Description:

Second dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy

Treatment:

Drug: methotrexate

Drug: folic acid

Drug: sarilumab SAR153191 (REGN88)

Sarilumab (SAR153191, REGN88) Dose 3

Experimental group

Description:

Third dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy

Treatment:

Drug: methotrexate

Drug: folic acid

Drug: sarilumab SAR153191 (REGN88)

Sarilumab (SAR153191, REGN88) Dose 4

Experimental group

Description:

Fourth dose of Sarilumab in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy

Treatment:

Drug: methotrexate

Drug: folic acid

Drug: sarilumab SAR153191 (REGN88)

Placebo Dose 5

Placebo Comparator group

Description:

Placebo to match Sarilumab (SAR153191, REGN88) in a single SC injection. Methotrexate (stable dose) and folic acid are continued as background therapy

Treatment:

Drug: placebo

Drug: methotrexate

Drug: folic acid