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

• ClinicalTrials.gov Identifier: NCT03449758
• Recruitment Status: Completed
• First Posted: February 28, 2018
• Results First Posted: August 10, 2020
• Last Update Posted: August 13, 2020
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: SARILUMAB; Drug: Azathioprine; Drug: Chloroquine; Drug: Hydroxychloroquine; Drug: Leflunomide; Drug: Methotrexate; Drug: Sulfasalazine	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 5, 2018
• Actual Primary Completion Date: July 31, 2019
• Actual Study Completion Date: July 31, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: SARILUMAB; Pharmaceutical form:Solution for injection in pre-filled syringe Route of administration: Subcutaneous; Other Names: SAR153191 (REGN88); Kevzara®; Drug: Azathioprine; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Chloroquine; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Hydroxychloroquine; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Leflunomide; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Methotrexate; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous / Intramuscular; Drug: Sulfasalazine; Pharmaceutical form:Tablet Route of administration: Oral

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24 [ Time Frame: Baseline, Week 24 ]
   RAID was a participant reported outcome measure used to evaluate the impact of RA on participant's quality of life which comprised 7 domains: • pain, • function, • fatigue, • physical and psychological well-being, • sleep disturbance, and • coping. Each domain was a single question scored on a 0 to 10 continuous NRS. The values for each of these domains were weighed by participant assessment of relative importance and combined in a single value. Total RAID score range was 0 (not affected, very good) to 10 (most affected), where higher value indicated worse status.

Secondary Outcome Measures :

1. Rheumatoid Arthritis Impact of Disease Total Score at Baseline, Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   RAID was a participant reported outcome measure used to evaluate the impact of RA on participant's quality of life which comprised 7 domains: • pain, • function, • fatigue, • physical and psychological well-being, • sleep disturbances, and • coping. Each domain was a single question scored on a 0 to 10 continuous NRS. The values for each of these domains were weighed by participant assessment of relative importance and combined in a single value. Total RAID score range was 0 (not affected, very good) to 10 (most affected), where higher value indicated worse status.
2. Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Weeks 4 and 12 [ Time Frame: Baseline, Weeks 4 and 12 ]
   RAID was a participant reported outcome measure used to evaluate the impact of RA on participant's quality of life which comprised 7 domains: • pain, • function, • fatigue, • physical and psychological wellbeing, • sleep disturbance, and • coping. Each domain was a single question scored on a 0 to 10 continuous NRS. The values for each of these domains were weighed by participant assessment of relative importance and combined in a single value. Total RAID score range was 0 (not affected, very good) to 10 (most affected), where higher value indicated worse status.
3. Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   HADS questionnaire measures the presence and severity of anxiety and depression in both hospital and community settings. The questionnaire comprised of 14 items divided into 2 subscales: 7 items for anxiety subscale (HADS-A) and 7 items for depression subscale (HADS-D). Each item was scored on a 0 to 3 rating scale. The anxiety and depression subscales each ranged from 0 to 21 (0-7: normal, 8-10: borderline abnormal and 11-21: abnormal), where higher scores indicated greater severity of anxiety/depression. The subscales were independent for each result of depression and anxiety.
4. Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   HADS questionnaire measures the presence and severity of anxiety and depression in both hospital and community settings. The questionnaire comprised of 14 items divided into 2 subscales: 7 items for anxiety subscale (HADS-A) and 7 items for depression subscale (HADS-D). Each item was scored on a 0 to 3 rating scale. The anxiety and depression subscales each ranged from 0 to 21 (0-7: normal, 8-10: borderline abnormal and 11-21: abnormal), where higher scores indicated greater severity of anxiety/depression. The subscales were independent for each result of depression and anxiety.
5. Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at Baseline, Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   MAThyS was a multi-dimensional self-administered questionnaire comprised of five dimensions (emotional reactivity, cognition speed, psychomotor function, motivation and sensory perception) divided into 20 items relating to individual states as perceived by participants for the preceding week (at each specified Week). Each item was measured on a visual analog scale (VAS; in centimeters [cm]) ranged from 0 (inhibition of the state evaluated by the item) to 10 (excitation for the evaluated state). Total MAThyS score was sum of the 20 items and that might vary from score range 0 to 200 with lower scores indicated general inhibition and higher scores indicated general excitation.
6. Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   MAThyS was a multi-dimensional self-administered questionnaire comprised of five dimensions (emotional reactivity, cognition speed, psychomotor function, motivation and sensory perception) divided into 20 items relating to individual states as perceived by participants for the preceding week (at each specified Week). Each item was measured on a VAS (in cm) ranging from 0 (inhibition of the state evaluated by the item) to 10 (excitation for the evaluated state). Total MAThyS score was sum of the 20 items and that might vary from score range 0 to 200 with lower scores indicated general inhibition and higher scores indicated general excitation.
7. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at Baseline, Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   FACIT-F was a 13-item questionnaire that assess fatigue in participants under chronic illness therapy. Participants scored each item on a 5-point Likert scale ranged from 0 to 4 (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The scores of each item were reversed during score calculations, so that higher score values indicated more favorable conditions. Total score was the sum of score from each item and resulted in a score range from 0 to 52, with higher score indicated better participant health status (lower level of fatigue).
8. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   FACIT-F was a 13-item questionnaire that assess fatigue in participants under chronic illness therapy. Participants scored each item on a 5-point Likert scale ranged from 0 to 4 (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The scores of each item were reversed during score calculations, so that higher score values indicated more favorable conditions. Total score was the sum of score from each item and resulted in a score range from 0 to 52, with higher score indicated better participant health status (lower level of fatigue).
9. Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
   HAQ-DI was a participant-oriented questionnaire developed specifically to assess the extent of a RA participant's functional ability. It consisted of at least 2 or 3 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week (at each specified visit) rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, and ranged from 0 to 3, where 0 = no disability and 3 = completely disabled, higher score indicated more disability.
10. Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    HAQ-DI was a participant-oriented questionnaire developed specifically to assess the extent of a RA participant's functional ability. It consisted of at least 2 or 3 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week (at each specified visit) rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, and ranged from 0 to 3, where 0 = no disability and 3 = completely disabled, higher score indicated more disability.
11. Duration of Morning Stiffness at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Duration of morning stiffness was defined as the time elapsed (in minutes) between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. At each specified time point, duration of morning stiffness was reported by the participant during the visit.
12. Change From Baseline in Duration of Morning Stiffness at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Duration of morning stiffness was defined as the time elapsed (in minutes) between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. At each specified time point, duration of morning stiffness was reported by the participant during the visit.
13. International Physical Activity Questionnaire (IPAQ) Total Score at Baseline, Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    IPAQ was a 27-item self-reported questionnaire designed to measure physical activity of participant. The score was reported in metabolic equivalent (MET)-minutes per week. MET minutes represented the amount of energy expended to carry out physical activity. For IPAQ total score, the minimum value is zero and there is no maximum. Higher scores mean better levels of physical activity.
14. Change From Baseline in International Physical Activity Questionnaire Total Score at Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    IPAQ was a 27-item self-reported questionnaire designed to measure physical activity of participant. The score was reported in MET minutes per week. MET minutes represented the amount of energy expended to carry out physical activity. For IPAQ total score, the minimum value is zero and there is no maximum. Higher scores mean better levels of physical activity.
15. Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at Baseline, Weeks 4, 12 and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    PtGA of disease activity was measured using a 100 millimeters (mm) horizontal VAS ranged from 0=no pain to 100=maximum pain imaginable, where higher score indicated more disease activity.
16. Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    PtGA of disease activity was measured using a 100 mm horizontal VAS ranged from 0=no pain to 100=maximum pain imaginable, where higher score indicated more disease activity.
17. Erythrocyte Sedimentation Rate (ESR) at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    ESR was a laboratory test to provide non-specific measure of inflammation in the body. The test assessed the rate at which red blood cells fell in a test tube and was measured in millimeter per hour (mm/h).
18. Change From Baseline in Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    ESR was a laboratory test to provide non-specific measure of inflammation in the body. The test assessed the rate at which red blood cells fell in a test tube and was measured in mm/h.
19. Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    DAS28-ESR was a composite score that included 4 variables: tender joint count (TJC) (based on 28 joints); swollen joint count (SJC) (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable); marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score ranged from 0-10, higher score indicated more disease activity. The DAS28-ESR score provided a number indicating the current disease activity of the RA. A DAS28-ESR score above 5.1 indicated high disease activity, DAS28-ESR score less than or equal to (<=) 3.2 indicated low disease activity (LDA), greater than (>) 3.2 to <=5.1 implied moderate disease activity and DAS28-ESR score below 2.6 indicated disease remission.
20. Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    DAS28-ESR was a composite score that included 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable); marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score ranged from 0-10, higher score indicated more disease activity. The DAS28-ESR score provided a number indicating the current disease activity of the RA. A DAS28-ESR score above 5.1 indicated high disease activity, DAS28-ESR score <= 3.2 indicated LDA, > 3.2 to <=5.1 implied moderate disease activity and DAS28-ESR score below 2.6 indicated disease remission.
21. Clinical Disease Activity Index (CDAI) Total Score at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    CDAI was a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global disease activity (in cm), and physician's global assessment of disease (in cm). CDAI total score ranges from 0 to 76 with a lower score indicating less disease activity. A CDAI score of <=2.8 represents clinical remission and a score of <=10.0 represents LDA.
22. Change From Baseline in Clinical Disease Activity Index Total Score at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    CDAI was a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global disease activity (in cm), and physician's global assessment of disease (in cm). CDAI total score ranges from 0 to 76 with a lower score indicating less disease activity. A CDAI score of <=2.8 represents clinical remission and a score of <=10.0 represents LDA.
23. Number of Swollen Joints at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Number of joints with swelling are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb).
24. Change From Baseline in Number of Swelling Joints at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Number of joints with swelling are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb).
25. Number of Tender Joints at Baseline, Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Number of joints with tenderness are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb).
26. Change From Baseline in Number of Tender Joints at Weeks 4, 12, and 24 [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Number of joints with tenderness are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb).
27. Number of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at Weeks 12, and 24 [ Time Frame: Weeks 12 and 24 ]
    DAS28-ESR was a composite score that included 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable) marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score ranged from 0-10, higher score indicated more disease activity. The DAS28-ESR score provided a number indicating the current disease activity of the RA. A DAS28-ESR score above 5.1 indicated high disease activity, DAS28-ESR score <= 3.2 indicated LDA, > 3.2 to <=5.1 implied moderate disease activity and DAS28-ESR score below 2.6 indicated disease remission.
28. 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 [ Time Frame: Weeks 12 and 24 ]
    CDAI was a composite index constructed to measure clinical remission in RA that does not included a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global disease activity (in cm), and physician's global assessment (in cm). Total score ranged from 0 to 76 with a lower score indicated less disease activity. A CDAI score of <=2.8 represents clinical remission and a score of <=10.0 represents LDA.
29. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to end of study (up to 39.7 weeks) ]
    An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the study treatment. SAE: Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that occurred in the time from the first injection of study drug up to 39.7 weeks.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

France

Investigational Site Number 250007

Argenteuil, France

Investigational Site Number 250006

Besancon, France, 25030

Investigational Site Number 250027

Bobigny, France, 93000

Investigational Site Number 250016

Bordeaux, France, 33076

Investigational Site Number 250014

Caen, France, 14033

Investigational Site Number 250032

CAHORS Cedex 9, France, 46005

Investigational Site Number 250019

Cannes, France, 06414

Investigational Site Number 250013

Cholet, France, 49325

Investigational Site Number 250002

Clermont Ferrand, France, 63003

Investigational Site Number 250009

Echirolles, France, 38434

Investigational Site Number 250005

La Roche Sur Yon, France, 85025

Investigational Site Number 250024

Le Mans Cedex 9, France, 72037

Investigational Site Number 250004

Lille Cedex, France, 59037

Investigational Site Number 250012

Limoges Cedex, France, 87000

Investigational Site Number 250021

Lyon, France, 69495

Investigational Site Number 250018

Montivilliers, France

Investigational Site Number 250029

MONTPELLIER Cedex 5, France, 34295

Investigational Site Number 250025

NANTES Cedex 1, France, 44035

Investigational Site Number 250026

Nice cedex 1, France, 06001

Investigational Site Number 250020

Paris Cedex 10, France, 75475

Investigational Site Number 250011

PARIS Cedex 13, France, 75013

Investigational Site Number 250010

Paris, France, 75012

Investigational Site Number 250015

Paris, France, 75014

Investigational Site Number 250028

Paris, France, 75015

Investigational Site Number 250033

Paris, France

Investigational Site Number 250031

Poitiers, France, 86021

Investigational Site Number 250023

Pontoise, France, 95300

Investigational Site Number 250017

RENNES Cedex, France, 35022

Investigational Site Number 250008

Rouen, France, 76000

Investigational Site Number 250001

St Etienne, France, 42055

Investigational Site Number 250034

Strasbourg Cedex 2, France, 67098

Investigational Site Number 250022

Toulouse, France, 31200

Investigational Site Number 250003

Tours, France, 37000

Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

  Study Documents (Full-Text)

Documents provided by Sanofi:

Study Protocol  [PDF] June 6, 2018

Statistical Analysis Plan  [PDF] November 19, 2019

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03449758
• Other Study ID Numbers: SARILL08755; U1111-1197-7699 ( Other Identifier: UTN ); 2017-002951-27 ( EudraCT Number )
• First Posted: February 28, 2018
• Results First Posted: August 10, 2020
• Last Update Posted: August 13, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to participant level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Participant level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Hydroxychloroquine; Chloroquine; Sulfasalazine; Methotrexate; Azathioprine; Leflunomide; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors; Antimalarials