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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01217814
• Other study ID #: ACT11575
• Secondary ID: 2010-021020-94U1
• Status: Terminated
• Phase: Phase 2
• First received: October 7, 2010
• Last updated: November 9, 2012
• Start date: November 2010
• Est. completion date: September 2011

Study information

• Verified date: November 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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-a blocker nonresponder. i.e.:

• Appropriate for previous TNF-a blocker therapy

• Lack of adequate clinical response after at least 3 months TNF-a 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Sarilumab
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Placebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Golimumab
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• methotrexate [MTX]
Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution)
• Folic/folinic acid
Pharmaceutical form: tablet Route of administration: oral

Locations

Country	Name	City	State
Colombia	Investigational Site Number 170004	Barranquilla
Colombia	Investigational Site Number 170005	Barranquilla
Colombia	Investigational Site Number 170007	Bucaramanga
Czech Republic	Investigational Site Number 203002	Uherske Hradiste
Italy	Investigational Site Number 380002	Firenze
Italy	Investigational Site Number 380005	Genova
Mexico	Investigational Site Number 484008	Durango
Mexico	Investigational Site Number 484002	Guadalajara
Spain	Investigational Site Number 724004	Oviedo
Spain	Investigational Site Number 724002	Valencia
United States	Investigational Site Number 840038	Austin	Texas
United States	Investigational Site Number 840026	Freehold	New Jersey
United States	Investigational Site Number 840025	Jackson	Tennessee
United States	Investigational Site Number 840043	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Colombia,  Czech Republic,  Italy,  Mexico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants who achieve 20% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR20]		12 weeks	No
Secondary	Percentage of participants who achieve 50% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR50]		12 weeks	No
Secondary	Percentage of participants who achieve 70% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR70]		12 weeks	No
Secondary	Disease Activity Score [DAS28]		12 weeks	No
Secondary	European League Against Rheumatism [EULAR] response		12 weeks	No
Secondary	Percentage of participants with DAS28 remission (DAS28 < 2.6)		12 weeks	No
Secondary	Incidence of Adverse Events		up to 18 weeks	Yes
Secondary	Serum concentration of functional and bound sarilumab		up to 18 weeks	No