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Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND)

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

SAR153191 (REGN88)

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria :

Main study:

Participants with RA who were previously randomized in the sarilumab RA clinical program: e.g., the EFC11072 study, ACT11575 study, EFC10832 study, SFY13370, and EFC13752 study.

Sub-study:

Participants enrolled in the LTS11210 study who were receiving either sarilumab 200mg q2w PFS or sarilumab 150mg q2w PFS and who were able and willing to participate in this sub-study.

Participants who had been enrolled in the main study for at least 24 weeks. Participants must sign a sub-study written informed consent prior to any sub-study related procedure.

Exclusion criteria:

Main study:

Participants with any adverse event (AE) led to permanent study drug discontinuation from a prior study.

Participants with an abnormality(ies) or AEs that per investigator judgment would adversely affect participation of the participant in the study.

Sub-study: There are no additional exclusion criteria to those defined in main study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)

Sarilumab monotherapy

Arm Description

Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.

Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily have to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product (IMP) in study LTS11210 to the last dose of the IMP +60 days).

Sub-study: Number of Participants Reported Product Technical Complaints (PTC), Product Technical Failures (PTF) and/or Failed Drug Deliveries (FDD) With Pre-filled Syringe With Safety System

A PTF was defined as any product technical complaint (PTC) related to the use of the PFS-S that had a validated technical cause. FDD was defined as participant's failure to administer the full dose at a given attempt. A PTC was defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary. The injection diary comprised specific questions: 1. Were you able to remove the cap? 2. Was the needle safety system activated?, 3. Did the safety system entirely cover the needle, and 4. Was the person who performed the injection the person who was trained by the site staff?, where each question was given the option yes/no. Participants who answered "no" for any of the questions of PTC, had PTF and/or FDD were reported in this outcome measure.

Sub-study: Number of Product Technical Complaints - Product Technical Failures With Pre-filled Syringe With Safety System

A PTF was defined as any PTC (defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary) related to the use of the PFS-S that had a validated technical cause. Number of PTF in the participants enrolled in sub-study were reported in this outcome measure.

Sub-study: Number of Failed Drug Deliveries Associated With Pre-filled Syringe With Safety System

FDD was defined as participant's failure to administer the full dose at a given attempt. Number of FDD in the participants enrolled in sub-study were reported in this outcome measure.

Sub-study: Number of Product Technical Complaints With Pre-filled Syringe With Safety System

A PTC was defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary. The injection diary comprised specific questions: 1. Were you able to remove the cap? 2. Was the needle safety system activated?, 3. Did the safety system entirely cover the needle, and 4. Was the person who performed the injection the person who was trained by the site staff?, where each question was given the option yes/no. Number of PTC (based on participant's answer to "no" for any of the questions of PTC) in the participants enrolled in sub-study were reported in this outcome measure.

Secondary Outcome Measures

Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response

ACR20 response: greater than or equal to (>=) 20% improvement in both tender joint count and swollen joint count and, >=20% improvement in at least 3 of the 5 remaining ACR core measures assessments: C-reactive protein [CRP] level (mg/liter [mg/L]); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] visual analog scale [VAS]); participant's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by health assessment questionnaire disability index [HAQ-DI], with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.

Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response

ACR50 response: >=50% improvement in both TJC and SJC, and >=50% improvement in at least 3 of the 5 remaining ACR core measures assessments: CRP level (in mg/L); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.

Percentage of Participants Achieving American College of Rheumatology 70 (ACR70) Response

ACR70 response: >=70% improvement in both TJC and SJC, and >=70% improvement in at least 3 of the 5 remaining ACR core measures assessments: CRP level (in mg/L); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.

Percentage of Participants With Disease Activity Score for 28 Joints (DAS28) Remission

Disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) was a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by the participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS). DAS28-CRP total score ranges from 0 to 10, where higher scores indicated greater disease activity. Percentage of participants with DAS28 remission were reported.

Percentage of Participants Achieving Good Response, Moderate Response or Non-response Using the European League Against Rheumatism (EULAR) Response Criteria

DAS28-based EULAR response criteria were used to measure individual response as none, good or moderate, depending on the extent of change from baseline and level of disease activity reached. The EULAR response criteria are defined as: Good response = change from baseline of >1.2 and a present DAS28-CRP score <=3.2. Moderate response = change from baseline of >0.6 to <=1.2 and a present DAS28-CRP score <=5.1, or, change from baseline of >1.2 and present DAS28-CRP score >3.2. Non-response = change from baseline of <=0.6, or change from baseline of >0.6 to <=1.2 and present DAS28-CRP score >5.1. Scores of good and moderate were considered to indicate therapeutic response. DAS28-CRP is a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS.

Change From Baseline in DAS28-CRP Score at Weeks 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

DAS28-CRP is a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by the participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS). DAS28-CRP total score ranges from 0-10, where higher scores indicated greater disease activity. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

HAQ-DI is a standardized questionnaire used to assess the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; hygiene; reach; grip and activities. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3, where 0= no difficulty in physical function; 1= some difficulty in physical function; 2= much difficulty in physical function; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty in physical function) to 3 (extreme difficulty in physical function), where higher scores indicate more difficulty while performing daily living activities. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 0 and Week 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B

Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both joint erosions (JE) for 44 joints and joint space narrowing (JSN) for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study Baseline in 2 years X-ray data at Week 0 and 48 of LTS11210 were reported.

Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B

Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 3 years X-ray data (participants with study duration of more than 48 weeks in LTS11210) at Week 48 and 96 of LTS11210 from Campaign 2 were reported.

Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 96, Week 144 and Week 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B

Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 5 years X-ray data (participants with study duration of more than 96 weeks in LTS11210) at Week 96, 144 and 192 of LTS11210 from Campaign 3 were reported.

Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 0 and 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B

Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 of LTS11210 from Campaign 1 X-ray data were reported.

Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B

Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 and 96 of LTS11210 from Campaign 2 X-ray data (participants with study duration of more than 48 weeks in LTS11210) were reported.

Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 96, 144 and 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B

Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 96, 144 and 192 of LTS11210 from Campaign 3 X-ray data (participants with study duration more than 96 weeks in LTS11210) were reported.

Change From Baseline in Tender Joint Count (TJC) at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

TJC is the sum of all tender joints based on examination of the 68 joints of the fingers, elbows, hips, knees, ankles, and toes. Total TJC ranged from 0 (best) to 68 (worst), where higher score = more severity. Change from Baseline in TJC was reported in the outcome measure. Here, Baseline refers to Baseline of initial study (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Swollen Joint Count (SJC) at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

SJC is the sum of all swollen joints based on examination of the fingers, elbows, knees and toes. Total SJC ranged from 0 (best) to 66 (worst), where higher score = more severity. Change from Baseline in SJC was reported in the outcome measure. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Physician's Global Assessments of Disease Activity Visual Analogue Scale (VAS) Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Physician global assessment of disease activity was measured on a 100 millimeters (mm) horizontal VAS, ranging from 0 (best disease activity) to 100 (worst disease activity), where lower score = less disease activity and higher score = more disease activity. Here, Baseline refers to Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Participant Global Assessment of Disease Activity Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Participant global assessment of disease activity was measured on a 100 mm horizontal VAS, ranging from 0 (best disease activity) to 100 (worst disease activity), where lower score = less disease activity and higher score = more disease activity. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Participant's Assessment of Pain Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Participants were requested to indicate their pain intensity due to their RA on a 100 mm horizontal VAS, ranging from 0 (no pain) to 100 (worst pain), where a higher score represented more pain due to RA. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).

Change From Baseline in Short Form 36 (SF-36; Version 2) Physical Component Summary (PCS) Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, ACT11575 and EFC10832 Only

SF-36 is a generic 36-item questionnaire consisting of 8 domains, measuring quality of life (QoL) covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and general health; and MCS with 4 domains: vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored by summing the individual items, which are transformed into a score range from 0 to 100; where 0= worst QoL to 100=best QoL. PCS total score ranged from 0 to 100 with higher scores indicating better physical health. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).

Change From Baseline in Short Form 36 (SF-36; Version 2) Mental Component Summary Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, ACT11575 and EFC10832 Only

SF-36 is a generic 36-item questionnaire consisting of 8 domains, measuring quality of life (QoL) covering 2 summary measures: PCS and MCS. PCS with 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and general health; and MCS with 4 domains: vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored by summing the individual items, which are transformed into a score range from 0 to 100; 0= worst QoL to 100=best QoL. MCS total score ranged from 0 to 100 with higher scores indicating better physical and mental health. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).

Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Total Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210-Participants From EFC11072, ACT11575 and EFC10832 Only

The FACIT-F is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0 to 4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. The sum of all responses resulted in the FACIT-Fatigue total score ranged from 0 to 52, where higher score = lower level of fatigue and indicates better QoL. A positive change from baseline score indicates an improvement. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).

Change From Baseline in Sleep Visual Analogue Scale Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only

Rheumatoid arthritis (RA), like other chronic illness, is associated with sleep disturbances and is linked to pain, mood, and disease activity. The effect of sarilumab on sleep was assessed on a on 100 mm horizontal VAS scale, ranging from 0 (sleep is not a problem) to 100 (sleep is a major problem), where higher score = more sleep disturbances. Here, Baseline refers to the Baseline of initial studies (EFC11072, and ACT11575).

Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to RA at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072 and ACT11575 Only

WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers indicated greater impairment). The percent work time missed due to RA was a subscale and calculated as: 100*Q2/(Q2+Q4) for those who were currently employed. Subscale score was expressed as impairment percentage (range:0 to 100%) where higher numbers indicate greater impairment and less productivity. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).

Change From Baseline in Work Productivity and Activity Impairment: Percent Impairment While Working Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only

WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers = less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers = greater impairment). Percentage impairment while working due to RA was subscale and calculated as: 10*Q5 for those who were currently employed and actually worked in past 7 days. Subscale score=expressed as impairment percentage (range:0 to 100%), where higher numbers=greater impairment and less productivity. Here, Baseline refers to the Baseline of initial studies (EFC11072 and ACT11575).

Change From Baseline in Work Productivity and Activity Impairment: Percent Overall Work Impairment Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only

WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 10 scale, with higher numbers indicated greater impairment). Percent overall work impairment due to RA was subscale and calculated as: 100*Q2/(Q2+Q4)+100*[(1- Q2/(Q2+Q4))*(Q5/10)] for those who were currently employed . Subscale score = expressed as impairment percentage (range: 0 to 100%) where higher numbers indicate greater impairment. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).

Change From Baseline in Work Productivity and Activity Impairment: Percent Activity Impairment Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only

WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 10 scale, with higher numbers indicated greater impairment). Percent activity impairment due to RA was a subscale and calculated as: 10*Q6 for all respondents. Subscale score=expressed as impairment percentage (range: 0 to 100%) where higher numbers indicate greater impairment. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).

Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Work Days Missed Due to Arthritis - Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with arthritis over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from Baseline in number of work days missed in the last month due to arthritis by the participant was reported in the outcome measure. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Work Productivity Reduced by >=50% Due to Arthritis - Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from Baseline in number of work days with reduced productivity by >= 50% in the last month by the participant was reported in the outcome measure. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Arthritis Interference With Work Productivity - Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranged from 0 (no interference) to 10 (complete interference), where higher scores indicated more interference. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: House Work Days Missed Due to Arthritis - Participants From EFC10832 Only

'The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with no household work/household work missed in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Household Work Productivity Reduced by >=50% Due to Arthritis - Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with reduced household work productivity by >= 50% in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Family/Social/Leisure Activities Missed Due to Arthritis - Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days missed of family/social/leisure activities in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Outside Help Hired Due to Arthritis- Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with outside help hired in the last month by the participant was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).

Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Arthritis Interference With Household Work Productivity - Participants From EFC10832 Only

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranged from 0 (no interference) to 10 (complete interference), where higher scores indicated more interference. Here, Baseline refers to the Baseline of initial study (EFC10832).

Sub-study: Number of Participants Who Reported Adverse Events Related to Pre-filled Syringe With Safety System

AEs related to PFS-S included PTC-related AEs, device-related AEs, or AEs of injection site reaction. In this outcome measure, only PTC-related AEs, device-related AEs, or AEs of injection site reaction assessed during the sub-study were reported. TEAEs and SAEs reported during the sub-study were included in the main study data and no separate data collection and analysis was performed, as pre-planned in the protocol .

Full Information

NCT ID

NCT01146652

First Posted

June 15, 2010

Last Updated

March 21, 2022

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01146652

Brief Title

Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND)

Official Title

A Multi-center, Uncontrolled Extension Study Evaluating Efficacy and Safety of SAR153191 in Patients With Active Rheumatoid Arthritis (RA)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

June 21, 2010 (Actual)

Primary Completion Date

December 31, 2020 (Actual)

Study Completion Date

December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Main Study: Primary Objective: Assess the long term safety of sarilumab in participants with rheumatoid arthritis (RA). Secondary Objective: Assess the long term efficacy of sarilumab in participants with RA. Sub-Study: This phase 3, open label sub-study was aimed to assess the usability of PFS-S when used by participants with moderate or severe RA, or their professional or non-professional healthcare providers in an unsupervised real-world situation. To mimic the real-world practice, the sub-study was incorporated into the LTS11210 study without additional visits compared to the scheduled visits in the main study. The duration of this sub-study was 12 weeks.

Detailed Description

The maximum duration of the study was up to 523 weeks: Up to 1-week of screening, if any. At least 264 weeks of open label treatment phase and up to 516 weeks as maximum. 6-week post-treatment follow-up as required per protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

2023 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)

Arm Type

Experimental

Arm Description

Arm Title

Sarilumab monotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

SAR153191 (REGN88)

Intervention Description

Pharmaceutical form: solution Route of administration: subcutaneous

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Description

Time Frame

From first dose (i.e., Day 1 of study LTS11210) up to 60 days after last dose (maximum duration: up to 523 weeks)

Title

Sub-study: Number of Participants Reported Product Technical Complaints (PTC), Product Technical Failures (PTF) and/or Failed Drug Deliveries (FDD) With Pre-filled Syringe With Safety System

Description

Time Frame

From Week 24 to 36

Title

Sub-study: Number of Product Technical Complaints - Product Technical Failures With Pre-filled Syringe With Safety System

Description

Time Frame

From Week 24 to 36

Title

Sub-study: Number of Failed Drug Deliveries Associated With Pre-filled Syringe With Safety System

Description

FDD was defined as participant's failure to administer the full dose at a given attempt. Number of FDD in the participants enrolled in sub-study were reported in this outcome measure.

Time Frame

From Week 24 to 36

Title

Sub-study: Number of Product Technical Complaints With Pre-filled Syringe With Safety System

Description

Time Frame

From Week 24 to 36

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response

Description

Time Frame

At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response

Description

Time Frame

At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Percentage of Participants Achieving American College of Rheumatology 70 (ACR70) Response

Description

Time Frame

At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Percentage of Participants With Disease Activity Score for 28 Joints (DAS28) Remission

Description

Time Frame

At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Title

Percentage of Participants Achieving Good Response, Moderate Response or Non-response Using the European League Against Rheumatism (EULAR) Response Criteria

Description

Time Frame

At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Title

Change From Baseline in DAS28-CRP Score at Weeks 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Title

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 0 and Week 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B

Description

Time Frame

Baseline, Week 0 and 48 of LTS11210

Title

Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B

Description

Time Frame

Baseline, Week 48 and 96 of LTS11210

Title

Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 96, Week 144 and Week 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B

Description

Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 5 years X-ray data (participants with study duration of more than 96 weeks in LTS11210) at Week 96, 144 and 192 of LTS11210 from Campaign 3 were reported.

Time Frame

Baseline, Week 96, 144 and 192 of LTS11210

Title

Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 0 and 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B

Description

Time Frame

Week 0 (post-dose) and 48 of LTS11210

Title

Description

Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 and 96 of LTS11210 from Campaign 2 X-ray data (participants with study duration of more than 48 weeks in LTS11210) were reported.

Time Frame

Week 48 and 96 of LTS11210

Title

Description

Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 96, 144 and 192 of LTS11210 from Campaign 3 X-ray data (participants with study duration more than 96 weeks in LTS11210) were reported.

Time Frame

Week 96, 144 and 192 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Title

Change From Baseline in Participant's Assessment of Pain Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Description

Time Frame

Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Change From Baseline in Sleep Visual Analogue Scale Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only

Description

Time Frame

Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Description

Time Frame

Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Title

Description

WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers = less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers = greater impairment). Percentage impairment while working due to RA was subscale and calculated as: 10*Q5 for those who were currently employed and actually worked in past 7 days. Subscale score=expressed as impairment percentage (range:0 to 100%), where higher numbers=greater impairment and less productivity. Here, Baseline refers to the Baseline of initial studies (EFC11072 and ACT11575).

Time Frame