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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Sarilumab; Drug: Placebo; Drug: Golimumab; Drug: methotrexate (MTX); Drug: Folic/folinic acid	Phase 2

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).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	16 participants
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
Study Start Date :	November 2010
Actual Primary Completion Date :	September 2011
Actual Study Completion Date :	September 2011

Arms and Interventions

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Arm	Intervention/treatment
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.

Outcome Measures

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Primary Outcome Measures :

1. 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 :

1. 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 ]
2. 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 ]
3. Disease Activity Score for 28 Joints (DAS28) at Week 12 [ Time Frame: Week 12 ]
4. European League Against Rheumatism (EULAR) Response at Week 12 [ Time Frame: Week 12 ]
5. Percentage of Participants Achieving DAS28 Remission Score < 2.6 at Week 12 [ Time Frame: Week 12 ]
6. Pharmacokinetic (PK) Parameter: Serum Concentration of Functional and Bound Sarilumab [ Time Frame: Week 12 ]

Eligibility Criteria

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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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations 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 Posted:	October 8, 2010
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