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

• Part A: Percentage of patients who achieved the American College of Rheumatology criteria for improvement ACR20 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Part B: ACR20 response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Part B: Change in modified Van der Heijde Sharp score (composite index on X-ray assessed through central reading) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
• Part B: Change in physical function as measured by the average change from baseline in HAQ-DI from Week 8 to Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

• Part B: Change in modified Van der Heijde Sharp score (composite index on X-ray assessed through central reading). [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
• Part B: Change in physical function as measured by the change from baseline in the Health Assessment Question-Disability (HAQ_DI) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
• Part B: Percentage of patients who achieved and maintained (for at least 6 months) an ACR70 response [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

Primary Objectives:

Part A: To demonstrate that SAR153191 (REGN88) on top of methotrexate (MTX) is effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks.

Part B: To demonstrate that SAR153191 (REGN88) added to MTX is 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 over 52 weeks

Secondary Objectives:

Part B:

To demonstrate that SAR153191 (REGN88) added to MTX is effective in:

- induction of a major clinical response at 52 weeks.

To assess the safety of SAR153191 (REGN88) added to MTX.

To document the pharmacokinetic profile of SAR153191 (REGN88) added to MTX, in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy.

The total study duration for a patient is 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 patients who will not continue in the long-term extension study).

'*' Patients successfully completing their treatment period will be offered the opportunity to enter the long term extension study LTS11210 (EXTEND).

• Drug: SAR153191 (REGN88)

  Pharmaceutical form: solution

  Route of administration: subcutaneous

• Drug: placebo

  Pharmaceutical form: solution

  Route of administration: subcutaneous

• Experimental: Part A: SAR153191 (REGN88) Dose 1
  SAR153191, 100mg every week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part A: SAR153191 (REGN88) Dose 2
  SAR153191, 150mg every week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part A: SAR53191 (REGN88) Dose 3
  SAR153191, 100mg, every-other-week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part A: SAR153191 (REGN88) Dose 4
  SAR153191, 150mg every-other-week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part A: SAR153191 (REGN88) Dose 5
  SAR153191, 200mg every-other-week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Placebo Comparator: Part A: Placebo
  Placebo on top of methotrexate
  Intervention: Drug: placebo
• Experimental: Part B: SAR153191 (REGN88) Dose 1
  SAR153191, 100mg every week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part B: SAR153191 (REGN88) Dose 2
  SAR153191, 150mg every week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part B: SAR153191 (REGN88) Dose 3
  SAR153191, 100mg every-other-week on top of methotrexate
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part B: SAR153191 (REGN88) Dose 4
  SAR153191, 150mg every-other-week on top of methotrexate (currently used dose after dose selection)
  Intervention: Drug: SAR153191 (REGN88)
• Experimental: Part B: SAR153191 (REGN88) Dose 5
  SAR153191, 200mg every-other-week on top of methotrexate (currently used dose after dose selection)
  Intervention: Drug: SAR153191 (REGN88)
• Placebo Comparator: Part B: Placebo
  Placebo on top of methotrexate
  Intervention: Drug: placebo

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 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 patient's potential participation in a clinical trial.