This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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: June 27, 2017
Last verified: June 2017
February 2, 2010
June 27, 2017
March 2010
October 2013   (Final data collection date for primary outcome measure)
  • 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.
  • Part A: Percentage of patients who achieved the American College of Rheumatology criteria for improvement ACR20 [ Time Frame: Week 12 ]
  • Part B: Percentage of patients who achieved ACR20 [ Time Frame: Week 24 ]
Complete list of historical versions of study NCT01061736 on ClinicalTrials.gov Archive Site
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.
  • Part B: Change in modified Van der Heijde Sharp score (composite index on X-ray assessed through central reading). [ Time Frame: Week 52 ]
  • 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 ]
  • Part B: Percentage of patients who achieved and maintained (for at least 6 months) an ACR70 response [ Time Frame: Week 52 ]
Not Provided
Not Provided
 
Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients
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

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.

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).

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Rheumatoid Arthritis
  • 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 100 mg qw
    Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks.
    Interventions:
    • Drug: Sarilumab
    • Drug: Methotrexate
    • Drug: Folic Acid
  • Experimental: Part A: SAR 150 mg qw
    Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks.
    Interventions:
    • Drug: Sarilumab
    • Drug: Methotrexate
    • Drug: Folic Acid
  • 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.
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo (for sarilumab)
    • Drug: Methotrexate
    • Drug: Folic Acid
  • Experimental: Part A: SAR 150 mg q2w
    Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks.
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo (for sarilumab)
    • Drug: Methotrexate
    • Drug: Folic Acid
  • Experimental: Part A: SAR 200 mg q2w
    Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks.
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo (for sarilumab)
    • Drug: Methotrexate
    • Drug: Folic Acid
  • Placebo Comparator: Part A: Placebo qw
    Placebo (for sarilumab) qw on top of MTX for 12 weeks.
    Interventions:
    • Drug: Placebo (for sarilumab)
    • Drug: Methotrexate
    • Drug: Folic Acid
  • 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).
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo (for sarilumab)
    • Drug: Methotrexate
    • Drug: Folic Acid
  • 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.
    Interventions:
    • Drug: Sarilumab
    • Drug: Methotrexate
    • Drug: Folic Acid
  • 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.
    Interventions:
    • Drug: Sarilumab
    • Drug: Methotrexate
    • Drug: Folic Acid
  • 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.
    Interventions:
    • Drug: Placebo (for sarilumab)
    • Drug: Methotrexate
    • Drug: Folic Acid

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1675
October 2013
October 2013   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Austria,   Belarus,   Belgium,   Brazil,   Canada,   Chile,   Colombia,   Czechia,   Egypt,   Estonia,   Finland,   Germany,   Greece,   Hungary,   India,   Korea, Republic of,   Lithuania,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Norway,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United States
Czech Republic
 
NCT01061736
EFC11072
2009-016266-90 ( EudraCT Number )
Yes
Not Provided
Not Provided
Sanofi
Sanofi
Regeneron Pharmaceuticals
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
Sanofi
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP