Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT03449758
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sarilumab 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. Sarilumab Azathioprine 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. Sarilumab Sulfasalazine 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. Sarilumab Chloroquine 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. Sarilumab Leflunomide 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. Sarilumab Methotrexate 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. Sarilumab Hydroxychloroquine 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24 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
Name Time Method Rheumatoid Arthritis Impact of Disease Total Score at Baseline, Weeks 4, 12 and 24 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.
Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Weeks 4 and 12 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.
Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Baseline, Weeks 4, 12, and 24 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.
Change From Baseline in Duration of Morning Stiffness at Weeks 4, 12, and 24 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.
International Physical Activity Questionnaire (IPAQ) Total Score at Baseline, Weeks 4, 12 and 24 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.
Change From Baseline in International Physical Activity Questionnaire Total Score at Weeks 4, 12 and 24 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.
Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at Baseline, Weeks 4, 12 and 24 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.
Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at Weeks 4, 12, and 24 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.
Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Weeks 4, 12 and 24 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.
Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at Baseline, Weeks 4, 12 and 24 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.
Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at Weeks 4, 12 and 24 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.
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at Baseline, Weeks 4, 12 and 24 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).
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at Weeks 4, 12 and 24 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).
Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 4, 12 and 24 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.
Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at Weeks 4, 12 and 24 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.
Duration of Morning Stiffness at Baseline, Weeks 4, 12, and 24 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.
Erythrocyte Sedimentation Rate (ESR) at Baseline, Weeks 4, 12, and 24 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).
Change From Baseline in Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24 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.
Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline, Weeks 4, 12, and 24 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.
Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24 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.
Number of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at Weeks 12, and 24 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.
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 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) 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.
Clinical Disease Activity Index (CDAI) Total Score at Baseline, Weeks 4, 12, and 24 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.
Change From Baseline in Clinical Disease Activity Index Total Score at Weeks 4, 12, and 24 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.
Number of Swollen Joints at Baseline, Weeks 4, 12, and 24 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).
Change From Baseline in Number of Swelling Joints at Weeks 4, 12, and 24 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).
Number of Tender Joints at Baseline, Weeks 4, 12, and 24 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).
Change From Baseline in Number of Tender Joints at Weeks 4, 12, and 24 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).
Trial Locations
- Locations (33)
Investigational Site Number 250014
🇫🇷Caen, France
Investigational Site Number 250006
🇫🇷Besancon, France
Investigational Site Number 250016
🇫🇷Bordeaux, France
Investigational Site Number 250007
🇫🇷Argenteuil, France
Investigational Site Number 250027
🇫🇷Bobigny, France
Investigational Site Number 250013
🇫🇷Cholet, France
Investigational Site Number 250032
🇫🇷CAHORS Cedex 9, France
Investigational Site Number 250019
🇫🇷Cannes, France
Investigational Site Number 250002
🇫🇷Clermont Ferrand, France
Investigational Site Number 250005
🇫🇷La Roche Sur Yon, France
Investigational Site Number 250009
🇫🇷Echirolles, France
Investigational Site Number 250024
🇫🇷Le Mans Cedex 9, France
Investigational Site Number 250004
🇫🇷Lille Cedex, France
Investigational Site Number 250012
🇫🇷Limoges Cedex, France
Investigational Site Number 250021
🇫🇷Lyon, France
Investigational Site Number 250018
🇫🇷Montivilliers, France
Investigational Site Number 250025
🇫🇷NANTES Cedex 1, France
Investigational Site Number 250029
🇫🇷MONTPELLIER Cedex 5, France
Investigational Site Number 250026
🇫🇷Nice cedex 1, France
Investigational Site Number 250023
🇫🇷Pontoise, France
Investigational Site Number 250020
🇫🇷Paris Cedex 10, France
Investigational Site Number 250033
🇫🇷Paris, France
Investigational Site Number 250031
🇫🇷Poitiers, France
Investigational Site Number 250011
🇫🇷PARIS Cedex 13, France
Investigational Site Number 250028
🇫🇷Paris, France
Investigational Site Number 250015
🇫🇷Paris, France
Investigational Site Number 250017
🇫🇷RENNES Cedex, France
Investigational Site Number 250008
🇫🇷Rouen, France
Investigational Site Number 250034
🇫🇷Strasbourg Cedex 2, France
Investigational Site Number 250001
🇫🇷St Etienne, France
Investigational Site Number 250010
🇫🇷Paris, France
Investigational Site Number 250022
🇫🇷Toulouse, France
Investigational Site Number 250003
🇫🇷Tours, France