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CompletedNCT03449758SariPROUpdated Apr 28, 2022Results posted

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

A Phase 4 interventional study of SARILUMAB and Azathioprine in Rheumatoid Arthritis, sponsored by Sanofi. Completed at 33 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-28.

Sponsored by Sanofi · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
84
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.
Read the 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.

02

Conditions studied

  • Rheumatoid Arthritis
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
84 participants (actual)

Study arms

  • 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 · Drug: Azathioprine · Drug: Chloroquine · Drug: Hydroxychloroquine · Drug: Leflunomide · Drug: Methotrexate · Drug: Sulfasalazine

Interventions

  • DrugSARILUMAB

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

    Also known as: SAR153191 (REGN88), Kevzara®

  • DrugAzathioprine

    Pharmaceutical form:Tablet Route of administration: Oral

  • DrugChloroquine

    Pharmaceutical form:Tablet Route of administration: Oral

  • DrugHydroxychloroquine

    Pharmaceutical form:Tablet Route of administration: Oral

  • DrugLeflunomide

    Pharmaceutical form:Tablet Route of administration: Oral

  • DrugMethotrexate

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

  • DrugSulfasalazine

    Pharmaceutical form:Tablet Route of administration: Oral

05

What researchers measure

Primary outcomes

  1. Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at 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.

    Time frame: Baseline, Week 24

Secondary outcomes

  1. Rheumatoid Arthritis Impact of Disease Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  2. Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at 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.

    Time frame: Baseline, Weeks 4 and 12

  3. Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  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

    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.

    Time frame: Baseline, Weeks 4, 12 and 24

  5. Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  6. Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  7. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  8. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  9. Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  10. Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  11. Duration of Morning Stiffness at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  12. Change From Baseline in Duration of Morning Stiffness at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  13. International Physical Activity Questionnaire (IPAQ) Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  14. Change From Baseline in International Physical Activity Questionnaire Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  15. Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  16. Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  17. Erythrocyte Sedimentation Rate (ESR) at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  18. Change From Baseline in Erythrocyte Sedimentation Rate at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  19. Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  20. Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  21. Clinical Disease Activity Index (CDAI) Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  22. Change From Baseline in Clinical Disease Activity Index Total Score at 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.

    Time frame: Baseline, Weeks 4, 12 and 24

  23. Number of Swollen Joints at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  24. Change From Baseline in Number of Swelling Joints at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  25. Number of Tender Joints at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  26. Change From Baseline in Number of Tender Joints at 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).

    Time frame: Baseline, Weeks 4, 12 and 24

  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

    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.

    Time frame: Weeks 12 and 24

  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

    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.

    Time frame: Weeks 12 and 24

  29. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    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.

    Time frame: Baseline up to end of study (up to 39.7 weeks)

06

Results

Posted Aug 10, 2020
Limitations and caveats
Secondary efficacy analyses was planned to be performed on the Per-protocol population (PPS), only when PPS represented less than 90 percent of the ITT population.

Participant flow

The study was conducted at 31 active centers in France. A total of 104 participants were screened between 05 March 2018 to 27 December 2018, of which 20 were screen failures. Screen failures were mainly due to inclusion criteria not met.

Participant flow — Overall Study
MilestoneSarilumab
Started84
Completed65
Not completed19
Withdrew: Major protocol deviation1
Withdrew: Treatment inefficacy5
Withdrew: Adverse event9
Withdrew: Consent withdrawal1
Withdrew: Other unspecified reason3

Outcome measures

PrimaryChange From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at 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.

Time frame:
Baseline, Week 24
Reported as:
Mean · score on a scale
Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24
score on a scaleSarilumab
Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24-2.4 ± 2.3
SecondaryRheumatoid Arthritis Impact of Disease Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Rheumatoid Arthritis Impact of Disease Total Score at Baseline, Weeks 4, 12 and 24
score on a scaleSarilumab
Week 44.6 ± 2.1
Week 123.9 ± 2.3
Week 243.3 ± 2.5
SecondaryChange From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at 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.

Time frame:
Baseline, Weeks 4 and 12
Reported as:
Mean · score on a scale
Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Weeks 4 and 12
score on a scaleSarilumab
Week 4-1.2 ± 1.6
Week 12-1.8 ± 2.2
SecondaryHospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Baseline, Weeks 4, 12, and 24
score on a scaleSarilumab
HADS-A: Baseline8.1 ± 4.3
HADS-A: Week 47.2 ± 4.3
HADS-A: Week 126.1 ± 3.7
HADS-A: Week 246.6 ± 3.9
HADS-D: Baseline7.0 ± 3.9
HADS-D: Week 46.6 ± 4.0
HADS-D: Week 125.7 ± 4.1
HADS-D: Week 245.5 ± 4.1
SecondaryChange From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Weeks 4, 12 and 24
score on a scaleSarilumab
HADS-A: Week 4-1.0 ± 2.4
HADS-A: Week 12-2.1 ± 3.3
HADS-A: Week 24-1.9 ± 3.2
HADS-D: Week 4-0.4 ± 2.5
HADS-D: Week 12-1.2 ± 4.1
HADS-D: Week 24-1.7 ± 3.7
SecondaryMultidimensional Assessment of Thymic States (MAThyS) Scale Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · cm
Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at Baseline, Weeks 4, 12 and 24
cmSarilumab
Baseline88.4 ± 21.1
Week 489.6 ± 20.3
Week 1294.8 ± 13.6
Week 2490.9 ± 22.3
SecondaryChange From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · cm
Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at Weeks 4, 12 and 24
cmSarilumab
Week 4-0.2 ± 24.2
Week 122.9 ± 17.7
Week 24-1.1 ± 23.4
SecondaryFunctional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at Baseline, Weeks 4, 12 and 24
score on a scaleSarilumab
Baseline25.5 ± 10.3
Week 421.0 ± 10.5
Week 1218.8 ± 9.7
Week 2417.9 ± 11.4
SecondaryChange From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at Weeks 4, 12 and 24
score on a scaleSarilumab
Week 4-4.8 ± 8.0
Week 12-6.4 ± 9.1
Week 24-7.6 ± 10.8
SecondaryStanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 4, 12 and 24
score on a scaleSarilumab
Baseline1.3 ± 0.8
Week 41.1 ± 0.7
Week 120.8 ± 0.7
Week 240.8 ± 0.8
SecondaryChange From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at Weeks 4, 12 and 24
score on a scaleSarilumab
Week 4-0.2 ± 0.5
Week 12-0.4 ± 0.6
Week 24-0.5 ± 0.8
SecondaryDuration of Morning Stiffness at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · minutes
Duration of Morning Stiffness at Baseline, Weeks 4, 12, and 24
minutesSarilumab
Baseline72.3 ± 75.0
Week 434.7 ± 43.9
Week 1228.9 ± 47.2
Week 2421.3 ± 37.5
SecondaryChange From Baseline in Duration of Morning Stiffness at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · minutes
Change From Baseline in Duration of Morning Stiffness at Weeks 4, 12, and 24
minutesSarilumab
Week 4-39.9 ± 67.9
Week 12-47.9 ± 76.8
Week 24-52.8 ± 72.3
SecondaryInternational Physical Activity Questionnaire (IPAQ) Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · MET minutes per week
International Physical Activity Questionnaire (IPAQ) Total Score at Baseline, Weeks 4, 12 and 24
MET minutes per weekSarilumab
Baseline1759.9 ± 1185.0
Week 41881.1 ± 1203.9
Week 122061.0 ± 1266.9
Week 242089.5 ± 1476.4
SecondaryChange From Baseline in International Physical Activity Questionnaire Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · MET minutes per week
Change From Baseline in International Physical Activity Questionnaire Total Score at Weeks 4, 12 and 24
MET minutes per weekSarilumab
Week 4175.6 ± 1177.7
Week 12533.4 ± 1509.7
Week 24382.0 ± 1719.8
SecondaryPatient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · mm
Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at Baseline, Weeks 4, 12 and 24
mmSarilumab
Baseline61.1 ± 22.4
Week 444.1 ± 25.6
Week 1236.6 ± 26.7
Week 2434.6 ± 25.6
SecondaryChange From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · mm
Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at Weeks 4, 12, and 24
mmSarilumab
Week 4-17.2 ± 24.2
Week 12-24.3 ± 31.8
Week 24-26.7 ± 29.6
SecondaryErythrocyte Sedimentation Rate (ESR) at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · mm/h
Erythrocyte Sedimentation Rate (ESR) at Baseline, Weeks 4, 12, and 24
mm/hSarilumab
Baseline28.8 ± 23.4
Week 410.5 ± 15.5
Week 129.2 ± 15.3
Week 248.4 ± 11.3
SecondaryChange From Baseline in Erythrocyte Sedimentation Rate at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · mm/h
Change From Baseline in Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24
mm/hSarilumab
Week 4-18.1 ± 21.1
Week 12-19.5 ± 25.1
Week 24-22.0 ± 23.2
SecondaryDisease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline, Weeks 4, 12, and 24
score on a scaleSarilumab
Baseline5.0 ± 1.2
Week 43.1 ± 1.5
Week 122.6 ± 1.5
Week 242.3 ± 1.4
SecondaryChange From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24
score on a scaleSarilumab
Week 4-1.8 ± 1.1
Week 12-2.3 ± 1.6
Week 24-2.7 ± 1.5
SecondaryClinical Disease Activity Index (CDAI) Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Clinical Disease Activity Index (CDAI) Total Score at Baseline, Weeks 4, 12, and 24
score on a scaleSarilumab
Baseline22.5 ± 11.2
Week 412.6 ± 9.8
Week 129.9 ± 10.4
Week 248.1 ± 7.8
SecondaryChange From Baseline in Clinical Disease Activity Index Total Score at 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.

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · score on a scale
Change From Baseline in Clinical Disease Activity Index Total Score at Weeks 4, 12, and 24
score on a scaleSarilumab
Week 4-9.8 ± 8.1
Week 12-12.2 ± 13.2
Week 24-14.6 ± 12.6
SecondaryNumber of Swollen Joints at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · joints
Number of Swollen Joints at Baseline, Weeks 4, 12, and 24
jointsSarilumab
Baseline6.3 ± 5.1
Week 42.5 ± 3.2
Week 121.9 ± 3.6
Week 241.6 ± 2.8
SecondaryChange From Baseline in Number of Swelling Joints at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · joints
Change From Baseline in Number of Swelling Joints at Weeks 4, 12, and 24
jointsSarilumab
Week 4-3.9 ± 4.3
Week 12-4.1 ± 5.1
Week 24-4.7 ± 5.2
SecondaryNumber of Tender Joints at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · joints
Number of Tender Joints at Baseline, Weeks 4, 12, and 24
jointsSarilumab
Baseline7.3 ± 5.8
Week 44.7 ± 5.4
Week 123.5 ± 5.2
Week 242.5 ± 4.1
SecondaryChange From Baseline in Number of Tender Joints at 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).

Time frame:
Baseline, Weeks 4, 12 and 24
Reported as:
Mean · joints
Change From Baseline in Number of Tender Joints at Weeks 4, 12, and 24
jointsSarilumab
Week 4-2.5 ± 4.5
Week 12-3.7 ± 6.5
Week 24-4.8 ± 6.4
SecondaryNumber of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at 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.

Time frame:
Weeks 12 and 24
Reported as:
Count of participants · Participants
Number of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at Weeks 12, and 24
ParticipantsSarilumab
LDA: Week 1212
LDA: Week 244
Remission: Week 1240
Remission: Week 2445
SecondaryNumber of Participants Achieving Clinical Disease Activity Index: Low Disease Activity (CDAI Score <=10.0) and Remission (CDAI Score <=2.8) 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.

Time frame:
Weeks 12 and 24
Reported as:
Count of participants · Participants
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
ParticipantsSarilumab
LDA: Week 1229
LDA: Week 2429
Remission: Week 1218
Remission: Week 2420
SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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.

Time frame:
Baseline up to end of study (up to 39.7 weeks)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
ParticipantsSarilumab
SAE10
TEAE76
AE leading to death0

Adverse events

Collected over All AEs were collected from the time of first injection of study drug up to 39.7 weeks regardless of seriousness or relationship to study drug.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sarilumab0/84 (0%)10/84 (11.9%)54/84 (64.3%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventSarilumab
NeutropeniaBlood and lymphatic system disorders1/84
Drug HypersensitivityImmune system disorders1/84
PneumoniaInfections and infestations1/84
Diabetes Mellitus Inadequate ControlMetabolism and nutrition disorders1/84
ArthritisMusculoskeletal and connective tissue disorders1/84
Back PainMusculoskeletal and connective tissue disorders1/84
Lumbar Spinal StenosisMusculoskeletal and connective tissue disorders1/84
Rheumatoid ArthritisMusculoskeletal and connective tissue disorders1/84
PolyneuropathyNervous system disorders1/84
Interstitial Lung DiseaseRespiratory, thoracic and mediastinal disorders1/84
Most frequent other events
Showing 10 of 11
Most frequent other events
EventSarilumab
NeutropeniaBlood and lymphatic system disorders16/84
NauseaGastrointestinal disorders10/84
BronchitisInfections and infestations10/84
AstheniaGeneral disorders9/84
FatigueGeneral disorders9/84
NasopharyngitisInfections and infestations9/84
HeadacheNervous system disorders9/84
PruritusSkin and subcutaneous tissue disorders6/84
DiarrhoeaGastrointestinal disorders5/84
Injection Site ErythemaGeneral disorders5/84

Baseline characteristics

Analysis was performed on intent-to-treat (ITT) population which included participants who met all the eligibility criteria and received study treatment at least once.

Age, Continuous
Age, Continuous(years)Sarilumab
Mean59.1 ± 12.3
Sex: Female, Male
Sex: Female, Male(Participants)Sarilumab
Female63
Male21
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Sarilumab
Rheumatoid Arthritis Impact of Disease (RAID) - Baseline Total Score
Rheumatoid Arthritis Impact of Disease (RAID) - Baseline Total Score(score on a scale)Sarilumab
Mean5.8 ± 1.9
07

Study locations

33 sites
  • Investigational Site Number 250007
    Argenteuil, France
  • Investigational Site Number 250006
    Besancon, 25030, France
  • Investigational Site Number 250027
    Bobigny, 93000, France
  • Investigational Site Number 250016
    Bordeaux, 33076, France
  • Investigational Site Number 250014
    Caen, 14033, France
  • Investigational Site Number 250032
    CAHORS Cedex 9, 46005, France
  • Investigational Site Number 250019
    Cannes, 06414, France
  • Investigational Site Number 250013
    Cholet, 49325, France
  • Investigational Site Number 250002
    Clermont Ferrand, 63003, France
  • Investigational Site Number 250009
    Echirolles, 38434, France
  • Investigational Site Number 250005
    La Roche Sur Yon, 85025, France
  • Investigational Site Number 250024
    Le Mans Cedex 9, 72037, France
  • Investigational Site Number 250004
    Lille Cedex, 59037, France
  • Investigational Site Number 250012
    Limoges Cedex, 87000, France
  • Investigational Site Number 250021
    Lyon, 69495, France
  • Investigational Site Number 250018
    Montivilliers, France
  • Investigational Site Number 250029
    MONTPELLIER Cedex 5, 34295, France
  • Investigational Site Number 250025
    NANTES Cedex 1, 44035, France
  • Investigational Site Number 250026
    Nice cedex 1, 06001, France
  • Investigational Site Number 250020
    Paris Cedex 10, 75475, France
  • Investigational Site Number 250011
    PARIS Cedex 13, 75013, France
  • Investigational Site Number 250010
    Paris, 75012, France
  • Investigational Site Number 250015
    Paris, 75014, France
  • Investigational Site Number 250028
    Paris, 75015, France
  • Investigational Site Number 250033
    Paris, France
  • Investigational Site Number 250031
    Poitiers, 86021, France
  • Investigational Site Number 250023
    Pontoise, 95300, France
  • Investigational Site Number 250017
    RENNES Cedex, 35022, France
  • Investigational Site Number 250008
    Rouen, 76000, France
  • Investigational Site Number 250001
    St Etienne, 42055, France
  • Investigational Site Number 250034
    Strasbourg Cedex 2, 67098, France
  • Investigational Site Number 250022
    Toulouse, 31200, France
  • Investigational Site Number 250003
    Tours, 37000, France
08

References and documents

Study documents

  • Study protocol · Jun 6, 2018
  • Statistical analysis plan · Nov 19, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient 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. Patient 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://vivli.org

09

Registry details

Key details

Study ID
NCT03449758
Lead sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
Responsible party
Sponsor
First posted
Feb 28, 2018
Start date
Mar 5, 2018
Primary completion
Jul 31, 2019
Completion
Jul 31, 2019
Results posted
Aug 10, 2020
Last update
Apr 28, 2022

Study contacts

Clinical Sciences & Operations
study director · Sanofi

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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