To Evaluate The Safety of SAR153191 (REGN88) and Tocilizumab Added to Other RA Drugs in Patients With RA Who Are Not Responding to or Intolerant of Anti-TNF Therapy (SARIL-RA-ASCERTAIN)

This study is currently recruiting participants.
Verified April 2014 by Sanofi
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01768572
First received: January 11, 2013
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

Primary Objective:

To assess, in the same study, the safety of sarilumab and tocilizumab in patients with rheumatoid arthritis (RA) who are inadequate responders to or intolerant of tumor necrosis factor (TNF) antagonists.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Double-Dummy Study Assessing The Safety and Tolerability of Sarilumab and Tocilizumab In Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF Antagonists

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Safety as measured by adverse events/serious adverse events, physical examinations, clinical laboratory, ECGs. [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: March 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR153191 (REGN88) Dose 1
A single subcutaneous injection of Dose 1 every two weeks added to hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide, plus placebo intravenous infusion every four weeks
Drug: sarilumab SAR153191 (REGN88)
Pharmaceutical form:solution Route of administration: subcutaneous
Experimental: SAR153191 (REGN88) Dose 2
A single subcutaneous injection of Dose 2 every two weeks added to hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide, plus placebo intravenous infusion every four weeks
Drug: sarilumab SAR153191 (REGN88)
Pharmaceutical form:solution Route of administration: subcutaneous
Active Comparator: Tocilizumab
Tocilizumab 4mg/kg up to 8 mg/kg (if needed), intravenous infusion every 4 weeks added to hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide, plus placebo subcutaneous injection every 2 weeks
Drug: tocilizumab
Pharmaceutical form:solution Route of administration: intravenous

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 with 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 RA, according to the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria with ≥ 3 months disease duration.

ACR Class I-III functional status, based on the 1991 revised criteria. Moderate-to-severely active RA. Anti-TNF therapy failures, defined as patients with an inadequate clinical response defined by the investigator, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 TNF-antagonist, resulting in or requiring their discontinuation. TNF-antagonists may include, but are not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab pegol.

Continuous treatment with one or a combination of non-biologic disease modifying antirheumatic drugs (DMARDs) for at least 12 consecutive weeks prior to screening and on a stable dose(s) for at least 6 consecutive weeks prior to screening:

  • Methotrexate - 10 to 25 mg/wk orally or parenteral (or per local labeling requirements if the dose range differs)
  • Leflunomide - 10 to 20 mg orally daily
  • Sulfasalazine (SSZ) - 1000 to 3000 mg orally daily
  • Hydroxychloroquine (HCQ) - 200 to 400 mg orally daily

Exclusion criteria:

Patients <18 years of age. Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening.

Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, or a change in dosage within 4 weeks prior to screening.

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 systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome.

Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the Screening Visit, whichever is longer.

Patients with active tuberculosis or latent tuberculosis infection. Prior or current history of interstitial lung disease. Prior treatment with anti-IL-6 or anti-IL-6R therapies, including but not limited to tocilizumab or sarilumab.

Treatment with anti-TNF agents, as follows:

  • Etanercept: within 28 days prior to randomization
  • Infliximab, adalimumab, golimumab, certolizumab pegol: within 42 days prior to randomization.

Treatment with RA-directed biologic agents with non- TNF-α antagonist mechanisms without adequate washout as follows:

  • Anakinra: within 28 days prior to randomization
  • Abatacept: within 42 days prior to randomization
  • Rituximab or other cell depleting agent: Within 6 months prior to randomization or until total lymphocyte count and CD 19+ lymphocyte count are normalized, or whichever is longer.

Prior treatment with a janus kinase (JAK) inhibitor (eg, tofacitinib). Patients with a history of invasive opportunistic infection. Prior or current history of malignancy, including lymphoproliferative diseases, 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.

Prior or current history of other significant concomitant illness(es) that, according to Investigator's judgment, would adversely affect the patient's participation in the study.

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: NCT01768572

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

  Show 84 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: NCT01768572     History of Changes
Other Study ID Numbers: SFY13370, 2012-003536-23, U1111-1133-7839
Study First Received: January 11, 2013
Last Updated: April 16, 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 23, 2014