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

Sanofi

Status and phase

Completed

Phase 4

Conditions

Rheumatoid Arthritis

Treatments

Drug: Leflunomide

Drug: SARILUMAB

Drug: Sulfasalazine

Drug: Azathioprine

Drug: Chloroquine

Drug: Hydroxychloroquine

Drug: Methotrexate

Study type

Interventional

Funder types

Industry

Identifiers

NCT03449758

U1111-1197-7699 (Other Identifier)

2017-002951-27 (EudraCT Number)

SARILL08755

Details and patient eligibility

About

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.

Full 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.

Enrollment

84 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

84 participants in 1 patient group

Sarilumab

Experimental group

Description:

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.

Treatment: