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

This study has been terminated.
(Due to delay in the study and the impact on the development timelines, not due to any identified safety concerns)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01217814
First Posted: October 8, 2010
Last Update Posted: September 1, 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 Objective:

- To demonstrate that sarilumab (SAR153191/REGN88) on top of methotrexate (MTX) was superior in efficacy to placebo for the relief of signs and symptoms of rheumatoid arthritis (RA), in participants with active RA who had failed up to 2 tumor necrosis factor-alpha (TNF-α) antagonists.

Secondary Objectives:

  • To assess the safety of sarilumab;
  • To 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
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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 MTX in Patients With Active 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 Achieved at Least 20% Improvement in American College of Rheumatology (ACR20) Core Set Disease Activity Index at Week 12 [ Time Frame: Week 12 ]

Secondary Outcome Measures:
  • Percentage of Participants Who Achieved at Least 50% Improvement in American College of Rheumatology (ACR50) Core Set Disease Activity Index at Week 12 [ Time Frame: Week 12 ]
  • Percentage of Participants Who Achieved at Least 70% Improvement in American College of Rheumatology Core (ACR70) Set Disease Activity Index at Week 12 [ Time Frame: Week 12 ]
  • Disease Activity Score for 28 Joints (DAS28) at Week 12 [ Time Frame: Week 12 ]
  • European League Against Rheumatism (EULAR) Response at Week 12 [ Time Frame: Week 12 ]
  • Percentage of Participants Achieving DAS28 Remission Score < 2.6 at Week 12 [ Time Frame: Week 12 ]
  • Pharmacokinetic (PK) Parameter: Serum Concentration of Functional and Bound Sarilumab [ Time Frame: Week 12 ]

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
Placebo Comparator: Placebo
Placebo 2 mL to match sarilumab once a week (qw) and 0.5 mL to match golimumab every 4 weeks (q4w) on top of MTX (15-25 mg) qw for 12 weeks.
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 Folic/folinic acid continued according to local standard.

Active Comparator: Golimumab 50 mg
Golimumab 50 mg q4w and placebo (matched to sarilumab) qw on top of MTX (15-25 mg) qw for 12 weeks.
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 Folic/folinic acid continued according to local standard.

Experimental: Sarilumab 150 mg
Sarilumab 150 mg qw and placebo (matched to golimumab) q4w on top of MTX (15-25 mg) qw for 12 weeks.
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 Folic/folinic acid continued according to local standard.


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

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 ≥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;
  • Participant 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 with MTX 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 was 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): 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
Czechia
Investigational Site Number 203002
Uherske Hradiste, Czechia, 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

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01217814     History of Changes
Other Study ID Numbers: ACT11575
2010-021020-94 ( EudraCT Number )
U1111-1115-3763 ( Other Identifier: UTN )
First Submitted: October 7, 2010
First Posted: October 8, 2010
Results First Submitted: May 23, 2017
Results First Posted: September 1, 2017
Last Update Posted: September 1, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Antibodies, Monoclonal
Leucovorin
Levoleucovorin
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
Antidotes
Protective Agents