To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)

This study is currently recruiting participants.
Verified April 2014 by Sanofi
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01709578
First received: October 15, 2012
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

Primary Objective:

To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) is effective for:

  • reduction of signs and symptoms at week 24 and
  • improvement of physical function over 24 weeks in patients with active rheumatoid arthritis (RA) who are inadequate responders or intolerant to tumor necrosis factor alpha (TNF-α) antagonists.

Secondary Objectives:

To investigate the effects of SAR153191 (REGN88) when added to DMARD therapy, in patients with active RA who are inadequate responders or intolerant to TNF-α antagonists, for:

  • reduction of signs and symptoms at 12 weeks,
  • improvement in physical function at 12 weeks,
  • improvement in disease activity as measured by other ACR derived components at Weeks 12 and 24, and
  • improvement in quality of life as measured by patient reported outcomes (PROs) at intermediate visits and Week 24.

To assess the safety of sarilumab in this population.

To assess the exposure of sarilumab added to DMARD therapy in this population.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: sarilumab SAR153191 (REGN88)
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • - The percentage of patients who achieved at least 20% improvement in the American College of Rheumatology (ACR) criteria [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]
  • Change in physical function as measured by the average of change from baseline in the health assessment questionnaire-disability index (HAQ-DI) from Wk 8 to Wk 24 [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients achieving American College of Rheumatology (ACR) 20/50/70 criteria [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  • Percentage of patients achieving American College of Rheumatology (ACR) 50/70 criteria [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]
  • Changes from baseline in disease activity score (DAS) 28 [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Disease activity score (DAS) 28 remission rate [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in short form (SF)-36 domains [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in the Rheumatoid Arthritis-Work Productivity Survey (WPS-RA) items [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in the Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-fatigue) [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in European Quality of Life-5 dimension (EQ-5D) [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in rheumatoid arthritis impact of disease (RAID) scores [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in each individual ACR component [ Time Frame: At Week 12 and Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 522
Study Start Date: October 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR153191 (REGN88) Dose 1
A single subcutaneous injection of Dose 1 on top of hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide
Drug: sarilumab SAR153191 (REGN88)
Pharmaceutical form:solution Route of administration: subcutaneous
Experimental: SAR153191 (REGN88) Dose 2
A single subcutaneous injection of Dose 2 on top of hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide
Drug: sarilumab SAR153191 (REGN88)
Pharmaceutical form:solution Route of administration: subcutaneous
Placebo Comparator: Placebo
A single subcutaneous injection of placebo on top of hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide
Other: placebo
Pharmaceutical form:solution Route of administration: subcutaneous

Detailed Description:

Total study duration is up to 34 weeks: Screening up to 28 days, Treatment phase of 24 weeks, and post-treatment follow-up of 6 weeks. After completion of the treatment phase of this study, patients are eligible to enter a long term safety study (LTS11210) for active treatment wit SAR153191 (REGN88).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: Diagnosis of rheumatoid arthritis ≥6 months duration, according to the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria (1). ACR Class I-III functional status, based on 1991 revised criteria (2). Anti-TNF therapy failures, defined by the investigator as patients with an inadequate clinical response, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 anti-TNF blocker(s), resulting in or requiring their discontinuation: TNF-blockers may include, but are not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab. Moderate-to-severely active rheumatoid arthritis. Continuous treatment with one or a combination of DMARDs (except for simultaneous combination use of leflunomide and methotrexate) for at least 12 weeks prior to baseline and on a stable dose(s) for at least 6 weeks prior to screening: Methotrexate - 6 to 25 mg/wk orally or parenterally Leflunomide - 10 to 20 mg orally daily Sulfasalazine - 1000 to 3000 mg orally daily Hydroxychloroquine - 200 to 400 mg orally daily. Exclusion criteria: Patients <18 years of age or legal adult age Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA. History of juvenile idiopathic arthritis or arthritis onset prior to age 16. Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome. Treatment with anti-TNF agents, as follows: o Within 28 days prior to the baseline visit - etanercept o Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab, certolizumab pegol Treatment with previous RA-directed biologic agents with other than TNF antagonist mechanisms: o Within 28 days prior to the randomization (baseline) visit - anakinra o Within 42 days prior to the randomization (baseline) visit - abatacept Within 6 months prior to the randomization (baseline) visit - any cell depleting agents including but not limited to rituximab without a normal lymphocyte and CD 19+ lymphocyte count. Treatment with any DMARD other than those allowed per protocol and limited to the maximum specified dosage within 12 weeks prior to baseline. Treatment with prednisone >10 mg or equivalent per day, or change in dosage within 4 weeks prior to baseline visit. Any parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline. Prior treatment with anti-IL-6 or IL-6R antagonist therapies, including tocilizumab or sarilumab, participation in a prior study of sarilumab, irrespective of treatment arm. Prior treatment with a Janus kinase inhibitor (such as tofacitinib). New treatment or dose-adjustment to ongoing medication for dyslipidemia within 6 weeks prior to randomization, ie, stable dose for at least 6 weeks prior to randomization. Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first investigational medicinal product (IMP) administration, whichever is longer. History of alcohol or drug abuse within 5 years prior to the screening visit. Patients with a history of malignancy other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization (baseline) visit. Nonmalignant lymphoproliferative disorders are also excluded. Patients with active tuberculosis or latent tuberculosis infection. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01709578

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

  Show 188 Study Locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01709578     History of Changes
Other Study ID Numbers: EFC10832, U1111-1115-8466
Study First Received: October 15, 2012
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 14, 2014