Trial Outcomes & Findings for Extension Study for Long Term Evaluation of SAR153191 (REGN88) in Patients With Ankylosing Spondylitis (NCT NCT01118728)

Last Updated: 2017-06-21

Results Overview

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, regardless of the relationship to the investigational medicinal product (IMP). SAE was any untoward medical occurrence that at any dose resulted in death or was life-threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the TEAE period (time from first dose of IMP up to the end of follow-up period).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

223 participants

Primary outcome timeframe

Baseline up to the end of study (66 weeks)

Results posted on

2017-06-21

Participant Flow

The study was conducted at 56 centers in 12 countries. A total of 224 participants were screened between 01 June 2010 and 03 June 2011.

Of 224 screened participants, 223 participants were enrolled and treated. One participant withdrew consent before randomization.

Participant milestones

Participant milestones
Measure	Sarilumab Sarilumab 150 mg subcutaneous (SC) injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Overall Study STARTED	223
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	223

Reasons for withdrawal

Reasons for withdrawal
Measure	Sarilumab Sarilumab 150 mg subcutaneous (SC) injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Overall Study Adverse Event	17
Overall Study Lack of Efficacy	27
Overall Study Sponsor's decision to discontinue study	172
Overall Study Withdrawal by Subject	3
Overall Study Lost to Follow-up	4

Baseline Characteristics

Extension Study for Long Term Evaluation of SAR153191 (REGN88) in Patients With Ankylosing Spondylitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sarilumab n=223 Participants Sarilumab 150 mg SC injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Age, Continuous	41.6 Years STANDARD_DEVIATION 11.3 • n=39 Participants
Sex: Female, Male Female	63 Participants n=39 Participants
Sex: Female, Male Male	160 Participants n=39 Participants

PRIMARY outcome

Timeframe: Baseline up to the end of study (66 weeks)

Population: Analysis was performed on safety population defined as all participants who received at least one dose of the study treatment after signature of the informed consent.

Outcome measures

Outcome measures
Measure	Sarilumab n=223 Participants Sarilumab 150 mg SC injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and Treatment Discontinuation Any TEAE	67.3 Percentage of participants
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and Treatment Discontinuation Any treatment-emergent SAE	5.4 Percentage of participants
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and Treatment Discontinuation Any TEAE leading to treatment discontinuation	8.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to the end of treatment (60 weeks)

Population: Analysis was performed on safety population. Number of participants analyzed=participants with ASAS20 assessment at specified time-points. Here 'n' signifies number of participants with available data for specified time-point.

Treatment response for ASAS20 was defined as: Improvement of ≥ 20% and ≥ 1 unit on a 0 (least) to 10 (worst) numerical rating score (NRS) in at least 3 of the 4 ASAS improvement criteria (ASASIC) domains, and no worsening of ≥ 20% and ≥ 1 unit on 0-10 NRS in the remaining domain. The 4 domains included were participant's global disease activity assessment, total back pain, physical function (Bath Ankylosing Spondylitis Functional Index), and Inflammation (mean of last 2 Bath Ankylosing Spondylitis Disease Activity Index questions on morning stiffness).

Outcome measures

Outcome measures
Measure	Sarilumab n=218 Participants Sarilumab 150 mg SC injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Percentage of Participants Who Achieved 20% Response in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) Week 0 (n=218)	30.3 Percentage of participants
Percentage of Participants Who Achieved 20% Response in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) Week 12 (n=207)	40.1 Percentage of participants
Percentage of Participants Who Achieved 20% Response in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) Week 24 (n=150)	46.0 Percentage of participants
Percentage of Participants Who Achieved 20% Response in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) Week 36 (n=93)	41.9 Percentage of participants
Percentage of Participants Who Achieved 20% Response in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) Week 48 (n=37)	59.5 Percentage of participants
Percentage of Participants Who Achieved 20% Response in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) Week 60 (n=7)	57.1 Percentage of participants

Adverse Events

Sarilumab

Serious events: 12 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sarilumab n=223 participants at risk Sarilumab 150 mg SC injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Infections and infestations Cellulitis	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Infections and infestations Diverticulitis	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Infections and infestations Gastroenteritis	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Infections and infestations Laryngitis	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Gastrointestinal disorders Crohn's disease	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Skin and subcutaneous tissue disorders Skin necrosis	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Musculoskeletal and connective tissue disorders Joint instability	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Renal and urinary disorders Nephrolithiasis	0.90% 2/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Investigations Tuberculin test positive	0.45% 1/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).

Other adverse events

Other adverse events
Measure	Sarilumab n=223 participants at risk Sarilumab 150 mg SC injection every week (or every other week in case of safety issue) for 260 weeks, or until commercially available, or until discontinuation of the project, whichever came first.
Infections and infestations Nasopharyngitis	7.2% 16/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Infections and infestations Upper respiratory tract infection	5.8% 13/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Blood and lymphatic system disorders Neutropenia	9.4% 21/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
Gastrointestinal disorders Aphthous stomatitis	5.4% 12/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).
General disorders Injection site reaction	6.3% 14/223 • All AEs were collected from signature of the informed consent form up to the final visit (Day 414) regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of IMP up to the end of follow-up period).

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER