Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients

Sanofi1,675 enrolled

Overview

Primary Objectives: Part A (dose ranging study): To demonstrate that sarilumab (SAR153191/REGN88) on top of MTX was effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks. Part B (pivotal study): To demonstrate that sarilumab added to MTX was effective in: * reduction of signs and symptoms of rheumatoid arthritis at 24 weeks * inhibition of progression of structural damage at 52 weeks * improvement in physical function at 16 weeks Secondary Objectives: Part B: To demonstrate that sarilumab added to MTX was effective in induction of a major clinical response at 52 weeks To assess the safety of sarilumab added to MTX To document the pharmacokinetic profile of sarilumab added to MTX in participants with active rheumatoid arthritis who were inadequate responders to MTX therapy.

The total study duration for a participant was 16-22 weeks (Part A) and 56-62 weeks (Part B) broken down as follows: * Screening: Up to 4 weeks * Treatment: 12 weeks (Part A) and 52 weeks (Part B)\* * Follow-up: 6 weeks (for participants who would not continue in the long-term extension study). '\*' Participants successfully completing their treatment period would be offered the opportunity to enter the long term extension study LTS11210 (SARIL-RA-EXTEND) (NCT01146652).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,675

Conditions

Rheumatoid Arthritis

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion criteria : * Diagnosis of rheumatoid arthritis ≥3 months duration * Active disease defined as: * at least 8/68 tender joints and 6/66 swollen joints, * high sensitivity C-reactive protein (hs-CRP) \>6 mg/l, * continuous treatment with MTX for at least 12 weeks prior to baseline visit and on stable dose for at least 6 weeks prior to screening visit. Part B only: * Bone erosion based on documented X-ray prior to first study drug intake, or * Cyclic Citrullinated Peptide (CCP) positive, or * Rheumatoid Factor (RF) positive. Exclusion criteria: * Age \<18 years or \>75 years. * Treatment with disease-modifying antirheumatic drugs (DMARDs) other than MTX within 4 weeks or 12 weeks prior to screening (depending on DMARDs). * Past history of non-response to prior Tumor Necrosis Factor (TNF) or biologic treatment. * Any past or current biologic agents for the treatment of rheumatoid arthritis within 3 months. * Use of parenteral glucocorticoids or intraarticular glucocorticoids within 4 weeks prior to screening visit. * Use of oral glucocorticoid greater than 10mg/day or equivalent/day, or a change in dosage within 4 weeks prior to baseline visit. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (262)

Investigational Site Number 840070

Anniston, Alabama, United States

Investigational Site Number 840004

Birmingham, Alabama, United States

Investigational Site Number 840072

Gilbert, Arizona, United States

Investigational Site Number 840029

Beverly Hills, California, United States

Investigational Site Number 840007

Palm Desert, California, United States

Outcomes

Primary Outcomes

Part A: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12

ACR20 response was defined, based on guidelines set forth by the American College of Rheumatology (ACR), as ≥20 % improvement in tender joint count and swollen joint count as well as ≥20% improvement in at least 3 of 5 following measures: C-Reactive Protein (CRP), Participant assessment of pain; Participant's global assessment of disease activity; Physician global assessment of disease activity; and Health Assessment Question-Disability Index (HAQ-DI). Missing data imputed by Last Observation Carried Forward (LOCF).

Time frame: Baseline to Week 12

Part B: Percentage of Participants Achieving ACR20 Response at Week 24

ACR20 improvement responses were determined without imputation of missing post-baseline values. In addition data collected after treatment discontinuation or rescue was set to missing. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.

Time frame: Baseline to Week 24

Part B: Change From Baseline in Health Assessment Question Disability Index (HAQ-DI) at Week 16

HAQ-DI was a participant-reported questionnaire that assesses the difficulty of performing daily activities: dress/groom, arise, eat, walk, reach, grip, hygiene and common activities. Overall score range from 0=least difficulty to 3=extreme difficulty. An increase in the score indicates a worsening of physical function while a decrease in the score represents improvement. Data collected after treatment discontinuation was set to missing.

Time frame: Baseline, Week 16

Part B: Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 52

The Sharp method modified by D. van der Heijde involves separate scores for erosions and joint space narrowing based on radiographs to assess the degree of structural damage. Total score range from 0 (normal) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Missing data were imputed by the linear extrapolation method.

Time frame: Baseline, Week 52

Secondary Outcomes

Part B: Percentage of Participants Achieving a Major Clinical Response at Week 52

Major clinical response was defined as an ACR70 response maintained for at least 24 consecutive weeks. ACR70 response uses the same criteria as for ACR20 but requires 70% improvement. In the primary approach, data collected after treatment discontinuation or rescue was set to missing. No imputation of missing post-baseline values was performed. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.

Time frame: Baseline up to Week 52