Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis

NCT ID: NCT03449758

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-05
• Study Completion Date: 2019-07-31

Brief Summary

Primary Objective:

To assess the effect of sarilumab in combination with conventional synthetic Disease-Modifying Anti-Rheumatic Drug (csDMARD) and/or monotherapy on participant-reported impact of disease, using the rheumatoid arthritis impact of disease (RAID) questionnaire, in participants with moderately to severely active rheumatoid arthritis (RA) and inadequate response or intolerance to current csDMARD or tumor necrosis factor (TNF) inhibitors.

Secondary Objectives:

• To assess the change of the RAID score from baseline (to Week 4, Week 12, and Week 24) in participants with moderately to severely active RA and inadequate response or intolerance to current csDMARD or TNF inhibitors, treated with sarilumab in combination with csDMARD and/or monotherapy.
• To assess the effect of sarilumab in combination with csDMARD and/or monotherapy on other participant-reported outcomes (global assessment of disease activity, disability, morning stiffness, fatigue, anxiety/depression, mood disorders, and physical activities) in participants with moderately to severely active RA and inadequate response or intolerance to current csDMARD or TNF inhibitors.
• To assess the efficacy of sarilumab in combination with csDMARD and/or monotherapy using disease activity score-28 for RA with erythrocyte sedimentation rate (DAS28-ESR) and clinical disease activity index in participants with moderately to severely active RA and inadequate response or intolerance to current csDMARD or TNF inhibitors.
• To assess the safety of sarilumab in combination with csDMARD and/or monotherapy in participants with moderately to severely active RA and inadequate response or intolerance to current csDMARD or TNF inhibitors.

Detailed Description

The study duration per participant was approximately 32 weeks, with up to 4-week screening, 24 weeks treatment period, and 2-4 weeks post-treatment observations.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sarilumab

Sarilumab 200 milligram (mg) subcutaneous (SC) injection every 2 weeks (q2w) from Day 1 of Week 0 up to Week 24 as monotherapy and/or in combination with methotrexate (MTX) or other csDMARD during the randomized 6-month (24 weeks) core treatment period. Participants completing 24 weeks period entered in a long-term extension treatment period and received sarilumab 200 mg q2w from Week 25 until the commercial availability of sarilumab in the country or maximum of up to Week 39.7.

Group Type: EXPERIMENTAL

SARILUMAB

Intervention Type: DRUG

Pharmaceutical form:Solution for injection in pre-filled syringe Route of administration: Subcutaneous

Azathioprine

Intervention Type: DRUG

Pharmaceutical form:Tablet Route of administration: Oral

Chloroquine

Intervention Type: DRUG

Pharmaceutical form:Tablet Route of administration: Oral

Hydroxychloroquine

Intervention Type: DRUG

Pharmaceutical form:Tablet Route of administration: Oral

Leflunomide

Intervention Type: DRUG

Pharmaceutical form:Tablet Route of administration: Oral

Methotrexate

Intervention Type: DRUG

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous / Intramuscular

Sulfasalazine

Intervention Type: DRUG

Pharmaceutical form:Tablet Route of administration: Oral

Interventions

SARILUMAB

Pharmaceutical form:Solution for injection in pre-filled syringe Route of administration: Subcutaneous

Intervention Type: DRUG

Azathioprine

Pharmaceutical form:Tablet Route of administration: Oral

Intervention Type: DRUG

Chloroquine

Pharmaceutical form:Tablet Route of administration: Oral

Intervention Type: DRUG

Hydroxychloroquine

Pharmaceutical form:Tablet Route of administration: Oral

Intervention Type: DRUG

Leflunomide

Pharmaceutical form:Tablet Route of administration: Oral

Intervention Type: DRUG

Methotrexate

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous / Intramuscular

Intervention Type: DRUG

Sulfasalazine

Pharmaceutical form:Tablet Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

SAR153191 (REGN88); Kevzara®

Eligibility Criteria

Inclusion Criteria

• Participants with moderately to severely active RA to European League against Rheumatology (EULAR)/American College of Rheumatology (ACR) Criteria.
• Participants with moderate to severe disease activity defined as a DAS28-ESR greater than (>) 3.2 at Screening.
• Participants with inadequate response within at least the last 3 months or intolerance to current csDMARD or to at least one anti-TNF therapy (as defined by the investigator).
• Oral corticosteroids (less than or equal to [<=] 15 mg/day prednisone or equivalent) and nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 (up to the maximum recommended dose) were allowed if taken at a stable dose for at least 4 weeks prior to Baseline.
• Permitted csDMARDs were allowed if taken at a stable dose for at least 4 weeks prior to Baseline.
• Participants abled and given written informed consent and complied with the requirements of the study protocol.

Exclusion Criteria

• Less than (<) 18 years of age.
• Participant unable to understand and write adequately to complete the study participant related outcome assessments.
• Exposure to sarilumab at any time prior to Baseline visit.
• Use of intra-articular or parenteral corticosteroids within 4 weeks prior to Baseline.
• Treatment with any investigational agent within the 4 weeks of Screening.
• Last RA treatment prior to inclusion with any anti-Janus kinase (JAK) or biologic DMARD other than anti-TNF.
• Participants treated with anti-TNF (i.e. adalimumab, infliximab, certolizumab, golimumab, etanercept) before the screening period, which are maintained within the 4 weeks before the inclusion (i.e. the first injection of sarilumab).
• Rheumatic autoimmune disease other than RA or prior history or current inflammatory joint disease other than RA.
• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri previously excised and cured).
• Participant who was institutionalized due to regulatory or legal order or participant who was mentally disabled or educationally disadvantaged.
• Pregnant or breastfeeding woman.
• Women of childbearing potential not protected by highly-effective contraceptive method(s) of birth control (as defined in the informed consent form and/or in a local protocol addendum/amendment) over the study period and for at least 3 months following the last dose of sarilumab, and/or who are unwilling or unable to be tested for pregnancy.
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies (or to any of the excipients associated to sarilumab).
• Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.
• Stage III or IV cardiac failure according to the New York Heart Association classification.
• History of previous gastrointestinal perforation or diverticulitis.
• Known active current/ recurrent infections (including but not limited to active tuberculosis [TB] or history of incompletely treated TB and atypical mycobacterial disease, hepatitis B and C, and herpes zoster). NOTE: in case of latent TB infection the participant might be included if a subsequent appropriate anti TB treatment is initiated since at least 3 weeks.
• Positive hepatitis B surface antigen, and/or positive total hepatitis B core antibody, and/or positive hepatitis C antibody at the Screening visit.
• Evidence of serious uncontrolled concomitant disease, including severe uncontrolled hypercholesterolemia or hypertriglyceridemia.
• Participants with any of the following laboratory abnormalities at the Screening or Baseline visit:

• Hemoglobin <8.5 grams per deciliter.
• White blood cells <3000/cubic millimeter (mm^3).
• Absolute neutrophil count <2000/mm^3
• Absolute lymphocyte count <500/mm^3
• Platelet count <150 000 cells/mm^3
• Creatinine clearance <30 milliliter per minute.
• Aspartate aminotransaminase or Alanine aminotransaminase >1.5 x upper limit of normal (ULN).
• Bilirubin (total) >ULN, unless Gilbert's disease has been determined by genetic testing and has been documented
• Total fasting cholesterol >3.50 gram per liter (g/L) [9.1 millimoles per liter {mmol/L}]) or triglycerides >5.00 g/L [5.6 mmol/L]).

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 250007

Argenteuil, , France

Investigational Site Number 250006

Besançon, , France

Investigational Site Number 250027

Bobigny, , France

Investigational Site Number 250016

Bordeaux, , France

Investigational Site Number 250014

Caen, , France

Investigational Site Number 250032

Cahors, , France

Investigational Site Number 250019

Cannes, , France

Investigational Site Number 250013

Cholet, , France

Investigational Site Number 250002

Clermont-Ferrand, , France

Investigational Site Number 250009

Échirolles, , France

Investigational Site Number 250005

La Roche-sur-Yon, , France

Investigational Site Number 250024

Le Mans, , France

Investigational Site Number 250004

Lille, , France

Investigational Site Number 250012

Limoges, , France

Investigational Site Number 250021

Lyon, , France

Investigational Site Number 250018

Montivilliers, , France

Investigational Site Number 250029

Montpellier, , France

Investigational Site Number 250025

Nantes, , France

Investigational Site Number 250026

Nice, , France

Investigational Site Number 250010

Paris, , France

Investigational Site Number 250011

Paris, , France

Investigational Site Number 250015

Paris, , France

Investigational Site Number 250028

Paris, , France

Investigational Site Number 250020

Paris, , France

Investigational Site Number 250033

Paris, , France

Investigational Site Number 250031

Poitiers, , France

Investigational Site Number 250023

Pontoise, , France

Investigational Site Number 250017

Rennes, , France

Investigational Site Number 250008

Rouen, , France

Investigational Site Number 250001

Saint-Etienne, , France

Investigational Site Number 250034

Strasbourg, , France

Investigational Site Number 250022

Toulouse, , France

Investigational Site Number 250003

Tours, , France

Countries

France

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1197-7699

Identifier Type: OTHER

Identifier Source: secondary_id

2017-002951-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SARILL08755

Identifier Type: -

Identifier Source: org_study_id