Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients (RA-MOBILITY)

Sanofi

Status and phase: Completed; Phase 3; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Methotrexate; Drug: Folic Acid; Drug: Placebo (for sarilumab); Drug: Sarilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01061736

EFC11072

2009-016266-90 (EudraCT Number)

Details and patient eligibility

About

Primary Objectives:

Part A (dose ranging study):

To demonstrate that sarilumab (SAR153191/REGN88) on top of MTX was effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks.

Part B (pivotal study):

To demonstrate that sarilumab added to MTX was effective in:

• reduction of signs and symptoms of rheumatoid arthritis at 24 weeks
• inhibition of progression of structural damage at 52 weeks
• improvement in physical function at 16 weeks

Secondary Objectives:

Part B:

To demonstrate that sarilumab added to MTX was effective in induction of a major clinical response at 52 weeks

To assess the safety of sarilumab added to MTX

To document the pharmacokinetic profile of sarilumab added to MTX in participants with active rheumatoid arthritis who were inadequate responders to MTX therapy.

Full description

The total study duration for a participant was 16-22 weeks (Part A) and 56-62 weeks (Part B) broken down as follows:

• Screening: Up to 4 weeks
• Treatment: 12 weeks (Part A) and 52 weeks (Part B)*
• Follow-up: 6 weeks (for participants who would not continue in the long-term extension study).

'*' Participants successfully completing their treatment period would be offered the opportunity to enter the long term extension study LTS11210 (SARIL-RA-EXTEND) (NCT01146652).

Enrollment: 1,675 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Diagnosis of rheumatoid arthritis ≥3 months duration

• Active disease defined as:

  • at least 8/68 tender joints and 6/66 swollen joints,
  • high sensitivity C-reactive protein (hs-CRP) >6 mg/l,
  • continuous treatment with MTX for at least 12 weeks prior to baseline visit and on stable dose for at least 6 weeks prior to screening visit.

Part B only:

• Bone erosion based on documented X-ray prior to first study drug intake, or
• Cyclic Citrullinated Peptide (CCP) positive, or
• Rheumatoid Factor (RF) positive.

Exclusion criteria:

• Age <18 years or >75 years.
• Treatment with disease-modifying antirheumatic drugs (DMARDs) other than MTX within 4 weeks or 12 weeks prior to screening (depending on DMARDs).
• Past history of non-response to prior Tumor Necrosis Factor (TNF) or biologic treatment.
• Any past or current biologic agents for the treatment of rheumatoid arthritis within 3 months.
• Use of parenteral glucocorticoids or intraarticular glucocorticoids within 4 weeks prior to screening visit.
• Use of oral glucocorticoid greater than 10mg/day or equivalent/day, or a change in dosage within 4 weeks prior to baseline visit.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,675 participants in 10 patient groups, including a placebo group

Part A: SAR 100 mg qw

Experimental group

Description:

Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks.

Treatment:

Drug: Folic Acid

Drug: Sarilumab

Drug: Methotrexate

Part A: SAR 150 mg qw

Experimental group

Description:

Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks.

Treatment:

Drug: Folic Acid

Drug: Sarilumab

Drug: Methotrexate

Part A: SAR 100 mg q2w

Experimental group

Description:

Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks.

Treatment:

Drug: Folic Acid

Drug: Placebo (for sarilumab)

Drug: Sarilumab

Drug: Methotrexate

Part A: SAR 150 mg q2w

Experimental group

Description:

Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks.

Treatment:

Drug: Folic Acid

Drug: Placebo (for sarilumab)

Drug: Sarilumab

Drug: Methotrexate

Part A: SAR 200 mg q2w

Experimental group

Description:

Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks.

Treatment:

Drug: Folic Acid

Drug: Placebo (for sarilumab)

Drug: Sarilumab

Drug: Methotrexate

Part A: Placebo qw

Placebo Comparator group

Description:

Placebo (for sarilumab) qw on top of MTX for 12 weeks.

Treatment:

Drug: Folic Acid

Drug: Placebo (for sarilumab)

Drug: Methotrexate

Part B Cohort 1: Non-selected Doses

Experimental group

Description:

Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210).

Treatment:

Drug: Folic Acid

Drug: Placebo (for sarilumab)

Drug: Sarilumab

Drug: Methotrexate

Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2)

Experimental group

Description:

Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab.

Treatment:

Drug: Folic Acid

Drug: Sarilumab

Drug: Methotrexate

Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2)

Experimental group

Description:

Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab.

Treatment:

Drug: Folic Acid

Drug: Sarilumab

Drug: Methotrexate

Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2)

Experimental group

Description:

Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab.

Treatment:

Drug: Folic Acid

Drug: Placebo (for sarilumab)

Drug: Methotrexate