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

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

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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Sarilumab; Drug: Placebo; Drug: methotrexate (MTX); Drug: Folic/folinic acid; Drug: Golimumab

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Colombia
  • Barranquilla, Colombia
    • Investigational Site Number 170004
  • Barranquilla, Colombia
    • Investigational Site Number 170005
  • Bucaramanga, Colombia
    • Investigational Site Number 170007
• Czechia
  • Uherske Hradiste, Czechia, 68601
    • Investigational Site Number 203002
• Italy
  • Firenze, Italy, 50141
    • Investigational Site Number 380002
  • Genova, Italy, 16132
    • Investigational Site Number 380005
• Mexico
  • Durango, Mexico, 34270
    • Investigational Site Number 484008
  • Guadalajara, Mexico, 44690
    • Investigational Site Number 484002
• Spain
  • Oviedo, Spain, 33006
    • Investigational Site Number 724004
  • Valencia, Spain, 46009
    • Investigational Site Number 724002
• United States
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Investigational Site Number 840026
  • New York
    • New York, New York, United States, 11201
      • Investigational Site Number 840043
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Investigational Site Number 840025
  • Texas
    • Austin, Texas, United States, 78705
      • Investigational Site Number 840038

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / 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: 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.; Drug: Golimumab; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Other Names: Simponi®
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Achieved at Least 20% Improvement in American College of Rheumatology (ACR20) Core Set Disease Activity Index at Week 12	Week 12

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: October 7, 2010
• First Submitted That Met QC Criteria: October 7, 2010
• First Posted (ESTIMATE): October 8, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Dermatologic Agents; Micronutrients; Vitamins; Reproductive Control Agents; Antidotes; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Tumor Necrosis Factor Inhibitors; Leucovorin; Levoleucovorin; Methotrexate; Folic Acid; Golimumab
• Other Study ID Numbers: ACT11575; 2010-021020-94 (EUDRACT_NUMBER); U1111-1115-3763 (OTHER: UTN)