We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    SAR 153191 mobility
Previous Study | Return to List | Next Study

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01061736
First Posted: February 3, 2010
Last Update Posted: June 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
  Purpose

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.


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
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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 Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline to Week 12 ]
    ACR20 response was defined, based on guidelines set forth by the American College of Rheumatology (ACR), as ≥20 % improvement in tender joint count and swollen joint count as well as ≥20% improvement in at least 3 of 5 following measures: C-Reactive Protein (CRP), Participant assessment of pain; Participant's global assessment of disease activity; Physician global assessment of disease activity; and Health Assessment Question-Disability Index (HAQ-DI). Missing data imputed by Last Observation Carried Forward (LOCF).

  • Part B: Percentage of Participants Achieving ACR20 Response at Week 24 [ Time Frame: Baseline to Week 24 ]
    ACR20 improvement responses were determined without imputation of missing post-baseline values. In addition data collected after treatment discontinuation or rescue was set to missing. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.

  • Part B: Change From Baseline in Health Assessment Question Disability Index (HAQ-DI) at Week 16 [ Time Frame: Baseline, Week 16 ]
    HAQ-DI was a participant-reported questionnaire that assesses the difficulty of performing daily activities: dress/groom, arise, eat, walk, reach, grip, hygiene and common activities. Overall score range from 0=least difficulty to 3=extreme difficulty. An increase in the score indicates a worsening of physical function while a decrease in the score represents improvement. Data collected after treatment discontinuation was set to missing.

  • Part B: Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 52 [ Time Frame: Baseline, Week 52 ]
    The Sharp method modified by D. van der Heijde involves separate scores for erosions and joint space narrowing based on radiographs to assess the degree of structural damage. Total score range from 0 (normal) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Missing data were imputed by the linear extrapolation method.


Secondary Outcome Measures:
  • Part B: Percentage of Participants Achieving a Major Clinical Response at Week 52 [ Time Frame: Baseline up to Week 52 ]
    Major clinical response was defined as an ACR70 response maintained for at least 24 consecutive weeks. ACR70 response uses the same criteria as for ACR20 but requires 70% improvement. In the primary approach, data collected after treatment discontinuation or rescue was set to missing. No imputation of missing post-baseline values was performed. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.


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: SAR 100 mg qw
Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of 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: SAR 150 mg qw
Sarilumab 150 mg SC injection qw on top of 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: SAR 100 mg q2w
Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of 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: SAR 150 mg q2w
Sarilumab 150 mg SC injection q2w alternating with placebo on top of 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: SAR 200 mg q2w
Sarilumab 200 mg SC injection q2w alternating with placebo on top of 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
Placebo (for sarilumab) qw on top of 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 Cohort 1: Non-selected Doses
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).
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: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2)
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.
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: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2)
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.
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: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2)
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.
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 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).

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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 participant's potential participation in a clinical trial.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01061736


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

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01061736     History of Changes
Other Study ID Numbers: EFC11072
2009-016266-90 ( EudraCT Number )
First Submitted: February 2, 2010
First Posted: February 3, 2010
Results First Submitted: May 23, 2017
Results First Posted: June 28, 2017
Last Update Posted: June 28, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Folic Acid
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Hematinics
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances