Effect of SAR153191 (REGN88) With Methotrexate in Patients With Active Rheumatoid Arthritis Who Failed TNF-α Blockers

This study has been terminated.
(The study was delayed and timelines impacted so that it would not allow completion in a reasonable timeframe for informing the future clinical development)
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01217814
First received: October 7, 2010
Last updated: November 9, 2012
Last verified: November 2012
  Purpose

Primary Objective:

- Demonstrate that sarilumab (SAR153191/REGN88) on top of methotrexate [MTX] is superior in efficacy to placebo for the relief of signs and symptoms of Rheumatoid Arthritis [RA], in patients with active RA who have failed up to 2 Tumor Necrosis Factor α [TNF-α] antagonists.

Secondary Objectives:

  • Assess the safety of sarilumab;
  • Document the pharmacokinetic profile of sarilumab.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Sarilumab
Drug: Placebo
Drug: Golimumab
Drug: methotrexate [MTX]
Drug: Folic/folinic acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, Placebo- and Active Calibrator-controlled Study Assessing the Clinical Benefit of SAR153191 Subcutaneous (SC) on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis (RA) Who Have Failed Previous TNF-α Antagonists

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of participants who achieve 20% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR20] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of participants who achieve 50% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR50] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who achieve 70% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR70] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Disease Activity Score [DAS28] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • European League Against Rheumatism [EULAR] response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants with DAS28 remission (DAS28 < 2.6) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Incidence of Adverse Events [ Time Frame: up to 18 weeks ] [ Designated as safety issue: Yes ]
  • Serum concentration of functional and bound sarilumab [ Time Frame: up to 18 weeks ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: November 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sarilumab 150 mg + MTX

Sarilumab 75 mg/mL, 2 ml once a week for 12 weeks, plus placebo (for golimumab), 0.5 ml every 4 weeks to maintain the blind, in addition to methotrexate [MTX], 15 to 25 mg once a week.

Folic/folinic acid continued according to local standard.

Drug: Sarilumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Names:
  • SAR153191
  • REGN88
Drug: Placebo

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: methotrexate [MTX]

Pharmaceutical form: tablet or solution for injection

Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)

Drug: Folic/folinic acid

Pharmaceutical form: tablet

Route of administration: oral

Placebo Comparator: Placebo + MTX

Placebo (for sarilumab), 2 ml once a week for 12 weeks, plus placebo (for golimumab), 0.5 ml every 4 weeks to maintain the blind, in addition to methotrexate [MTX], 15 to 25 mg once a week.

Folic/folinic acid continued according to local standard.

Drug: Placebo

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: methotrexate [MTX]

Pharmaceutical form: tablet or solution for injection

Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)

Drug: Folic/folinic acid

Pharmaceutical form: tablet

Route of administration: oral

Active Comparator: Golimumab 50 mg + MTX

Golimumab 50 mg/0.5 ml, 0.5 ml every 4 weeks for 12 weeks, plus placebo (for sarilumab), 2 ml once a week to maintain the blind, in addition to methotrexate [MTX], 15 to 25 mg once a week.

Folic/folinic acid continued according to local standard.

Drug: Placebo

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Drug: Golimumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Other Name: Simponi®
Drug: methotrexate [MTX]

Pharmaceutical form: tablet or solution for injection

Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)

Drug: Folic/folinic acid

Pharmaceutical form: tablet

Route of administration: oral


Detailed Description:

The duration of the study period for each participant was approximately 22 weeks; including up to 4 weeks screening period, 12-week double-blind treatment period and 6-week safety follow-up period.

Participants who completed the 12-week treatment period were offered enrollment in a separate long-term extension study (LTS11210/NCT01146652).

  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 ≥6 months duration and American College of Rheumatology [ACR] Class I-III functional status at screening and baseline visits;
  • Active disease defined as:

    • At least 6 of 68 tender joints and 6 of 66 swollen joints at screening and baseline visits, and
    • hs-C-Reactive Protein [hs-CRP] >10 g/L or Erythrocyte Sedimentation Rate [ESR] >28 mm/hr at screening visit;
  • Continuous treatment with Methotrexate for at least 12 weeks and on stable dose (minimum 10 mg/week) for at least 6 weeks prior to the screening visit;
  • Patient considered as Primary TNF-α blocker nonresponder. i.e.:

    • Appropriate for previous TNF-α blocker therapy
    • Lack of adequate clinical response after at least 3 months TNF-α blocker therapy (up to 2 agents) with Methotrexate or other synthetic disease modifying anti-rheumatic drug [DMARD] co-therapy.

Exclusion criteria:

  • Age <18 years or >75 years;
  • Pregnant or breastfeeding woman or woman of childbearing potential, unwilling to utilize adequate contraception or not to become pregnant during the entire study;
  • Fever (>38°C), or chronic, persistent, or recurring infection(s);
  • History of demyelinating disease;
  • Current underlying hepatobiliary disease.

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: NCT01217814

Locations
United States, New Jersey
Investigational Site Number 840026
Freehold, New Jersey, United States, 07728
United States, New York
Investigational Site Number 840043
New York, New York, United States, 11201
United States, Tennessee
Investigational Site Number 840025
Jackson, Tennessee, United States, 38305
United States, Texas
Investigational Site Number 840038
Austin, Texas, United States, 78705
Colombia
Investigational Site Number 170004
Barranquilla, Colombia
Investigational Site Number 170005
Barranquilla, Colombia
Investigational Site Number 170007
Bucaramanga, Colombia
Czech Republic
Investigational Site Number 203002
Uherske Hradiste, Czech Republic, 68601
Italy
Investigational Site Number 380002
Firenze, Italy, 50141
Investigational Site Number 380005
Genova, Italy, 16132
Mexico
Investigational Site Number 484008
Durango, Mexico, 34270
Investigational Site Number 484002
Guadalajara, Mexico, 44690
Spain
Investigational Site Number 724004
Oviedo, Spain, 33006
Investigational Site Number 724002
Valencia, Spain, 46009
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01217814     History of Changes
Other Study ID Numbers: ACT11575, 2010-021020-94, U1111-1115-3763
Study First Received: October 7, 2010
Last Updated: November 9, 2012
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
Levoleucovorin
Folic Acid
Methotrexate
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on October 19, 2014