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

NCT01217814 | Terminated Phase 2 Results DMC

• 3 other identifiers: ACT115752010-021020-94U1111-1115-3763
• Study Type: interventional
• Target: 16
• Locations: 6 countries
• Sites: 14

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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; Drug: methotrexate (MTX); Drug: Folic/folinic acid

Golimumab 50 mg

ACTIVE COMPARATOR

Golimumab 50 mg q4w and placebo (matched to sarilumab) qw on top of MTX (15-25 mg) qw for 12 weeks.

Drug: Placebo; Drug: Golimumab; Drug: methotrexate (MTX); Drug: Folic/folinic acid

Sarilumab 150 mg

EXPERIMENTAL

Sarilumab 150 mg qw and placebo (matched to golimumab) q4w on top of MTX (15-25 mg) qw for 12 weeks.

Drug: Sarilumab; Drug: Placebo; Drug: methotrexate (MTX); Drug: Folic/folinic acid

Interventions

Sarilumab DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Also known as: SAR153191, REGN88

Sarilumab 150 mg

Placebo DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Golimumab 50 mg; Placebo; Sarilumab 150 mg

Golimumab DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Also known as: Simponi®

Golimumab 50 mg

methotrexate (MTX) DRUG

Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)

Golimumab 50 mg; Placebo; Sarilumab 150 mg

Folic/folinic acid DRUG

Pharmaceutical form: tablet Route of administration: oral Folic/folinic acid continued according to local standard.

Golimumab 50 mg; Placebo; Sarilumab 150 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (14)

Investigational Site Number 840026

Freehold, New Jersey, 07728, United States

Location

Investigational Site Number 840043

New York, New York, 11201, United States

Location

Investigational Site Number 840025

Jackson, Tennessee, 38305, United States

Location

Investigational Site Number 840038

Austin, Texas, 78705, United States

Location

Investigational Site Number 170004

Barranquilla, Colombia

Location

Investigational Site Number 170005

Barranquilla, Colombia

Location

Investigational Site Number 170007

Bucaramanga, Colombia

Location

Investigational Site Number 203002

Uherské Hradiště, 68601, Czechia

Location

Investigational Site Number 380002

Florence, 50141, Italy

Location

Investigational Site Number 380005

Genova, 16132, Italy

Location

Investigational Site Number 484008

Durango, 34270, Mexico

Location

Investigational Site Number 484002

Guadalajara, 44690, Mexico

Location

Investigational Site Number 724004

Oviedo, 33006, Spain

Location

Investigational Site Number 724002

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sarilumab; golimumab; Methotrexate; Leucovorin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes

Limitations and Caveats

The study was prematurely terminated due to small number of participants entering randomization.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 8, 2010
• Study Start: November 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: September 1, 2017
• Results First Posted: September 1, 2017

Record last verified: 2017-07

Locations

ES (2); CO (3); CZ (1); ME (2); US (4); IT (2)