Clinical trial NCT03449758: Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis
Official title: Effect of Sarilumab on Patient-reported Outcomes in Patients With Moderately to Severely Active Rheumatoid Arthritis and With Inadequate Response or Intolerance to Current Conventional Synthetic DMARDs or Tumor Necrosis Factor Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-02-28
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Rheumatoid Arthritis Impact of Disease Total Score at Baseline, Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Weeks 4 and 12
timeFrame: Baseline, Weeks 4 and 12
measure: Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at Baseline, Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at Baseline, Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Duration of Morning Stiffness at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Duration of Morning Stiffness at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: International Physical Activity Questionnaire (IPAQ) Total Score at Baseline, Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in International Physical Activity Questionnaire Total Score at Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at Baseline, Weeks 4, 12 and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Erythrocyte Sedimentation Rate (ESR) at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Clinical Disease Activity Index (CDAI) Total Score at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Clinical Disease Activity Index Total Score at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Number of Swollen Joints at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Number of Swelling Joints at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Number of Tender Joints at Baseline, Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Change From Baseline in Number of Tender Joints at Weeks 4, 12, and 24
timeFrame: Baseline, Weeks 4, 12 and 24
measure: Number of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at Weeks 12, and 24
timeFrame: Weeks 12 and 24
measure: Number of Participants Achieving Clinical Disease Activity Index: Low Disease Activity (CDAI Score <=10.0) and Remission (CDAI Score <=2.8) Weeks 12, and 24
timeFrame: Weeks 12 and 24
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to end of study (up to 39.7 weeks)
Other outcomes:
Locations:
city: Argenteuil
country: France
facility: Investigational Site Number 250007
city: Besancon
country: France
facility: Investigational Site Number 250006
city: Bobigny
country: France
facility: Investigational Site Number 250027
city: Bordeaux
country: France
facility: Investigational Site Number 250016
city: Caen
country: France
facility: Investigational Site Number 250014
city: CAHORS Cedex 9
country: France
facility: Investigational Site Number 250032
city: Cannes
country: France
facility: Investigational Site Number 250019
city: Cholet
country: France
facility: Investigational Site Number 250013
city: Clermont Ferrand
country: France
facility: Investigational Site Number 250002
city: Echirolles
country: France
facility: Investigational Site Number 250009
city: La Roche Sur Yon
country: France
facility: Investigational Site Number 250005
city: Le Mans Cedex 9
country: France
facility: Investigational Site Number 250024
city: Lille Cedex
country: France
facility: Investigational Site Number 250004
city: Limoges Cedex
country: France
facility: Investigational Site Number 250012
city: Lyon
country: France
facility: Investigational Site Number 250021
city: Montivilliers
country: France
facility: Investigational Site Number 250018
city: MONTPELLIER Cedex 5
country: France
facility: Investigational Site Number 250029
city: NANTES Cedex 1
country: France
facility: Investigational Site Number 250025
city: Nice cedex 1
country: France
facility: Investigational Site Number 250026
city: Paris Cedex 10
country: France
facility: Investigational Site Number 250020
city: PARIS Cedex 13
country: France
facility: Investigational Site Number 250011
city: Paris
country: France
facility: Investigational Site Number 250010
city: Paris
country: France
facility: Investigational Site Number 250015
city: Paris
country: France
facility: Investigational Site Number 250028
city: Paris
country: France
facility: Investigational Site Number 250033
city: Poitiers
country: France
facility: Investigational Site Number 250031
city: Pontoise
country: France
facility: Investigational Site Number 250023
city: RENNES Cedex
country: France
facility: Investigational Site Number 250017
city: Rouen
country: France
facility: Investigational Site Number 250008
city: St Etienne
country: France
facility: Investigational Site Number 250001
city: Strasbourg Cedex 2
country: France
facility: Investigational Site Number 250034
city: Toulouse
country: France
facility: Investigational Site Number 250022
city: Tours
country: France
facility: Investigational Site Number 250003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: