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

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01061736
First received: February 2, 2010
Last updated: November 19, 2014
Last verified: November 2014
  Purpose

Primary Objectives:

Part A (dose ranging study):

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

Part B (pivotal study):

To demonstrate that sarilumab 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 at 16 weeks

Secondary Objectives:

Part B:

To demonstrate that sarilumab added to MTX is 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 patients with active rheumatoid arthritis who are inadequate responders to MTX therapy.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Sarilumab
Drug: Placebo (for sarilumab)
Drug: Methotrexate
Drug: Folic Acid
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Part A: Percentage of patients who achieved the American College of Rheumatology score of 20% improvement (ACR20) at Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Part B: Percentage of patients who achieved ACR20 response at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Part B: Change from baseline in modified Van der Heijde Sharp score (mTSS) at Week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Composite index on X-ray assessed through central reading

  • Part B: Change from baseline in Health Assessment Question-Disability Index (HAQ-DI) at Week 16 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part B: Percentage of patients who achieved the American College of Rheumatology score of 70% improvement (ACR70) for at least 24 consecutive weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 1675
Study Start Date: March 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: Sarilumab 100 mg qw + MTX
Sarilumab 100 mg every week (qw) on top of Methotrexate (MTX) for 12 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part A: Sarilumab 150 mg qw + MTX
Sarilumab 150 mg every week (qw) on top of Methotrexate (MTX) for 12 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part A: Sarilumab 100 mg q2w + MTX
Sarilumab 100 mg every other week (q2w) alternating with placebo on top of Methotrexate (MTX) for 12 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part A: Sarilumab 150 mg q2w + MTX
Sarilumab 150mg every other week (q2w) alternating with placebo on top of Methotrexate (MTX) for 12 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part A: Sarilumab 200 mg q2w + MTX
Sarilumab 200mg every other week (q2w) alternating with placebo on top of Methotrexate (MTX) for 12 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Placebo Comparator: Part A: Placebo qw + MTX
Placebo (for sarilumab) every week (qw) on top of Methotrexate (MTX) for 12 weeks
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part B: Sarilumab 100 mg qw + MTX
Sarilumab 100mg every week (qw) on top of Methotrexate (MTX) for 52 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part B: Sarilumab 150 mg qw + MTX
Sarilumab 150mg every week (qw) on top of Methotrexate (MTX) for 52 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part B: Sarilumab 100 mg q2w + MTX
Sarilumab 100mg every other week (q2w) alternating with placebo on top of Methotrexate (MTX) for 52 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part B: Sarilumab 150 mg q2w + MTX
Sarilumab 150mg every other week (q2w) alternating with placebo on top of Methotrexate (MTX) for 52 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Experimental: Part B: Sarilumab 200 mg q2w + MTX
Sarilumab 200mg every other week (q2w) alternating with placebo on top of Methotrexate (MTX) for 52 weeks
Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard
Placebo Comparator: Part B: Placebo qw + MTX
Placebo (for sarilumab) every week (qw) on top of Methotrexate (MTX) for 52 weeks
Drug: Placebo (for sarilumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Methotrexate
Same weekly dose as received prior to enrollment
Drug: Folic Acid
According to local standard

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01061736

  Show 262 Study Locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Principal Investigator: Mark C Genovese, MD, Professor of Medicine Division of Immunonoly and Rheumatology - Stanford University - USA
Study Chair: TWJ Huizinga, Prof Dr Dpt of Rheumatology - Leiden University Medical Center - The Netherlands
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01061736     History of Changes
Other Study ID Numbers: EFC11072, 2009-016266-90
Study First Received: February 2, 2010
Last Updated: November 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015