Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Bimekizumab in Subjects With Active Ankylosing Spondylitis
Summary
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EudraCT number |
2017-003065-95 |
Trial protocol |
DE BE HU GB BG FR ES CZ NL |
Global end of trial date |
08 Aug 2022
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Results information
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Results version number |
v2(current) |
This version publication date |
06 Feb 2025
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First version publication date |
19 Aug 2023
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AS0011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03928743 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
UCB Biopharma SRL
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Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, 1070
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Public contact |
UCB BIOSCIENCES GmbH, Clin Trial Reg & Results Disclosure, clinicaltrials@ucb.com
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Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Sep 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Sep 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Aug 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Demonstrate the efficacy of bimekizumab administered subcutaneously (sc) compared to placebo in the treatment of subjects with active ankylosing spondylitis (AS)
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Protection of trial subjects |
During the conduct of the study all participants were closely monitored.
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Background therapy |
Background therapy as permitted in the protocol. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
25 Apr 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Bulgaria: 15
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Country: Number of subjects enrolled |
China: 44
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Country: Number of subjects enrolled |
Belgium: 10
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Country: Number of subjects enrolled |
Czechia: 56
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Country: Number of subjects enrolled |
France: 4
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Country: Number of subjects enrolled |
Germany: 37
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Japan: 12
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Country: Number of subjects enrolled |
Poland: 87
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Country: Number of subjects enrolled |
Spain: 34
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Country: Number of subjects enrolled |
United Kingdom: 12
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Country: Number of subjects enrolled |
United States: 9
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Türkiye: 5
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Worldwide total number of subjects |
332
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EEA total number of subjects |
250
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
321
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
The study started to enroll study participants in April 2019 and concluded in August 2022. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The Participant Flow refers to the Randomized Set. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Double-Blind Treatment Period:Weeks 1-16
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo (up to Week 16) | |||||||||||||||||||||||||||
Arm description |
Participants received placebo matched to bimekizumab 160 milligrams (mg) every 4 weeks (Q4W) subcutaneously until Week 16. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received placebo Q4W at prespecified time points.
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Arm title
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Bimekizumab 160 mg Q4W (up to Week 16) | |||||||||||||||||||||||||||
Arm description |
Participants received bimekizumab 160 mg Q4W subcutaneously until Week 16. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Bimekizumab
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Investigational medicinal product code |
UCB4940
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received bimekizumab 160 mg Q4W at prespecified time points.
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Period 2
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Period 2 title |
Maintenance Period: Weeks 16-52
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||
Arms
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Arm title
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Bimekizumab 160 mg Q4W (Week 16 up to Week 52) | |||||||||||||||||||||||||||
Arm description |
At the end of the 16-week Double-Blind Treatment Period, study participants receiving placebo were re-allocated to bimekizumab treatment at Week 16. Participants received bimekizumab 160 mg Q4W subcutaneously from Week 16 until Week 48. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Bimekizumab
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Investigational medicinal product code |
UCB4940
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received bimekizumab 160 mg Q4W at prespecified time points.
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 3 participants completed the Double-blind treatment period but did not enter the Maintenance Period because of the below reason for discontinuation: Adverse event: 1; Withdrawal by study participants: 2 |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo (up to Week 16)
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Reporting group description |
Participants received placebo matched to bimekizumab 160 milligrams (mg) every 4 weeks (Q4W) subcutaneously until Week 16. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bimekizumab 160 mg Q4W (up to Week 16)
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Reporting group description |
Participants received bimekizumab 160 mg Q4W subcutaneously until Week 16. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Double Blind Treatment Period (up to Week 16): Placebo
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants received placebo matched to bimekizumab 160 mg Q4W subcutaneously until Week 16.
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Subject analysis set title |
Double Blind Treatment Period(up to Week 16):Bimekizumab160 mg
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants received bimekizumab 160 mg Q4W subcutaneously until Week 16.
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Subject analysis set title |
Maintenance Period (Weeks 16 to 52): Bimekizumab 160 mg
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
At the end of the 16-week Double-Blind Treatment Period, study participants receiving placebo were re-allocated to bimekizumab treatment at Week 16. All Participants received bimekizumab 160 mg Q4W subcutaneously from Week 16 until Week 48.
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Subject analysis set title |
Overall Period (up to Week 48+20 Weeks SFU):Bimekizumab 160 mg
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants who received bimekizumab 160 mg Q4W subcutaneously from Day 1 and participants who switched from placebo arm at Week 16 to receive bimekizumab 160 mg Q4W subcutaneously were included in this group.
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End points reporting groups
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Reporting group title |
Placebo (up to Week 16)
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Reporting group description |
Participants received placebo matched to bimekizumab 160 milligrams (mg) every 4 weeks (Q4W) subcutaneously until Week 16. | ||
Reporting group title |
Bimekizumab 160 mg Q4W (up to Week 16)
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Reporting group description |
Participants received bimekizumab 160 mg Q4W subcutaneously until Week 16. | ||
Reporting group title |
Bimekizumab 160 mg Q4W (Week 16 up to Week 52)
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Reporting group description |
At the end of the 16-week Double-Blind Treatment Period, study participants receiving placebo were re-allocated to bimekizumab treatment at Week 16. Participants received bimekizumab 160 mg Q4W subcutaneously from Week 16 until Week 48. | ||
Subject analysis set title |
Double Blind Treatment Period (up to Week 16): Placebo
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received placebo matched to bimekizumab 160 mg Q4W subcutaneously until Week 16.
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Subject analysis set title |
Double Blind Treatment Period(up to Week 16):Bimekizumab160 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received bimekizumab 160 mg Q4W subcutaneously until Week 16.
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Subject analysis set title |
Maintenance Period (Weeks 16 to 52): Bimekizumab 160 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
At the end of the 16-week Double-Blind Treatment Period, study participants receiving placebo were re-allocated to bimekizumab treatment at Week 16. All Participants received bimekizumab 160 mg Q4W subcutaneously from Week 16 until Week 48.
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Subject analysis set title |
Overall Period (up to Week 48+20 Weeks SFU):Bimekizumab 160 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received bimekizumab 160 mg Q4W subcutaneously from Day 1 and participants who switched from placebo arm at Week 16 to receive bimekizumab 160 mg Q4W subcutaneously were included in this group.
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End point title |
Percentage of Participants With Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 16 | ||||||||||||
End point description |
ASAS40 response: relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 (not active) and 10 (very active) in at least 3 of 4 domains:Patient's Global Assessment of Disease Activity (PGADA) assessed disease activity on a scale of 0 [not active] to 10 [very active], higher score=more disease activity, Pain assessment on a scale of 0 [no pain] to 10 [most severe pain], higher score=more severity), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)) assessed participant's level of ability on a scale of 0 [easy] to 10 [impossible], Inflammation (morning stiffness intensity and duration, mean of Q5 and Q6 of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) defined as 6 item questionnaire: measured disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity) and no worsening at all in remaining domain.Randomized Set consisted of all randomized study participants.
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End point type |
Primary
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End point timeframe |
Week 16
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
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Number of subjects included in analysis |
332
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.88
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.71 | ||||||||||||
upper limit |
4.87 |
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End point title |
Percentage of Participants With Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response in TNFα inhibitor-naïve participants at Week 16 | ||||||||||||
End point description |
ASAS40 response was defined as relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 NRS, where 0 (not active) and 10 (very active) in at least 3 of the 4 domains: PGADA assessed disease activity on a scale of 0 [not active] to 10 [very active], higher score=more disease activity, Pain assessment on a scale of 0 [no pain] to 10 [most severe pain], higher score=more severity), Function (BASFI) assessed participant's level of ability on a scale of 0 [easy] to 10 [impossible], Inflammation (morning stiffness intensity and duration, mean of Q5 and Q6 of BASDAI defined as 6 item questionnaire: measured disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity) and no worsening at all in the remaining domain. The Randomized Set consisted of all randomized study participants. Here, Number of Participants Analyzed signifies those who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Week 16
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
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Number of subjects included in analysis |
278
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.59 | ||||||||||||
upper limit |
4.93 |
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End point title |
Percentage of Participants With Assessment of SpondyloArthritis International Society 20% response criteria (ASAS20) response at Week 16 | ||||||||||||
End point description |
ASAS20 response was defined as relative improvements of at least 20% and absolute improvement of at least 1 unit on a 0 to 10 NRS, where 0 (not active) and 10 (very active) in at least 3 of the 4 domains: PGADA assessed disease activity on a scale of 0 [not active] to 10 [very active], higher score=more disease activity, Pain assessment on a scale of 0 [no pain] to 10 [most severe pain], higher score=more severity), Function (BASFI) assessed participant's level of ability on a scale of 0 [easy] to 10 [impossible], Inflammation (morning stiffness intensity and duration, mean of Q5 and Q6 of BASDAI defined as 6 item questionnaire: measured disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity) and no worsening at all in the remaining domain. The Randomized Set consisted of all randomized study participants.
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End point type |
Secondary
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End point timeframe |
Week 16
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
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Number of subjects included in analysis |
332
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.66
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.65 | ||||||||||||
upper limit |
4.28 |
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End point title |
Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) total score at Week 16 | ||||||||||||
End point description |
BASDAI is a validated self-reported instrument, which consisted of 6 questions to measure the disease activity of ankylosing spondylitis (AS) from the participant's perspective. It measured the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration). Each question was rated using a numerical rating scale from 0 (none) to 10 (very severe), higher score=high disease activity. The BASDAI score was calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions 1 to 4. This score was then divided by 5. The total BASDAI score was ranged from 0=none to 10= very severe, where higher score indicated high disease activity. A negative value indicated improvement and a positive value indicated worsening. The Randomized Set consisted of all randomized study participants.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
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Number of subjects included in analysis |
332
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
-1.04
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.48 | ||||||||||||
upper limit |
-0.59 |
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End point title |
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR) at Week 16 | ||||||||||||
End point description |
The Assessment of SpondyloArthritis International Society partial remission was defined as a score of less than or equal to (<=) 2 units (on a scale of 0-10, where 0=no disease activity and 10=high disease activity) in each of the 4 domains. These 4 domains included: PGADA assessed disease activity on a scale of 0 [not active] to 10 [very active], higher score=more disease activity, Pain assessment on a scale of 0 [no pain] to 10 [most severe pain], higher score=more severity), Function (BASFI) assessed participant's level of ability on a scale of 0 [easy] to 10 [impossible], Inflammation (morning stiffness intensity and duration, mean of Q5 and Q6 of BASDAI defined as 6 item questionnaire: measured disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity). The Randomized Set consisted of all randomized study participants.
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End point type |
Secondary
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End point timeframe |
Week 16
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
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Number of subjects included in analysis |
332
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
4.26
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.93 | ||||||||||||
upper limit |
9.39 |
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End point title |
Percentage of Participants With Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) at Week 16 | ||||||||||||
End point description |
ASDAS-MI is achieved when there is a reduction (improvement) of greater than or equal to (>=) 2.0 in the Ankylosing Spondylitis Disease Activity Score (ASDAS) relative to Baseline. ASDAS is calculated as the sum of the following components: 1) 0.121 × Total back pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q2 result), 2) 0.058 × Duration of morning stiffness (BASDAI Q6 result), 3) 0.110 × Patient's Global Assessment of Disease Activity (PGADA), 4) 0.073 × Peripheral pain/swelling (BASDAI Q3 result), 5) 0.579 × (natural logarithm of the C-reactive protein (CRP) [mg/L] + 1). Total back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). High ASDAS scores mean worse disease. If a participant achieves the ASDAS-MI it indicates a major improvement of their disease. The Randomized Set consisted of all randomized study participants.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
6.47
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
2.67 | ||||||||||||
upper limit |
15.65 |
|
|||||||||||||
End point title |
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 5/6 response at Week 16 | ||||||||||||
End point description |
The Assessment of SpondyloArthritis International Society (ASAS) 5/6 response is defined as achieving at least 20% improvement in 5 of 6 domains: PGADA assessed disease activity on a scale of 0 [not active] to 10 [very active], higher score=more disease activity, Pain assessment on a scale of 0 [no pain] to 10 [most severe pain], higher score=more severity), Function (BASFI) assessed participant's level of ability on a scale of 0 [easy] to 10 [impossible], Inflammation (morning stiffness intensity and duration, mean of Q5 and Q6 of BASDAI defined as 6 item questionnaire: measured disease activity on a scale of 0 [none] to 10 [severe], higher score=more disease activity), spinal mobility (lateral spinal flexion) and high sensitivity C-reactive protein (hs-CRP)]. The Randomized Set consisted of all randomized study participants.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
4.65
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
2.51 | ||||||||||||
upper limit |
7.57 |
|
|||||||||||||
End point title |
Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16 | ||||||||||||
End point description |
The Bath Ankylosing Spondylitis Functional Index (BASFI) assesses physical function in comprising 10 items relating to activities during the past week. Each item ranged from 0 ('Easy') to 10 ('Impossible'). The BASFI is the mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating better physical function. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. The Randomized Set consisted of all randomized study participants.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
-1.05
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.48 | ||||||||||||
upper limit |
-0.63 |
|
|||||||||||||
End point title |
Change from Baseline in nocturnal spinal pain score Numeric Rating Scale (NRS) at Week 16 | ||||||||||||
End point description |
Nocturnal spinal pain experienced by ankylosing spondylitis (AS) participants is measured by one question: pain in the spine at night due to AS?. When responding, the participant is to consider the average amount of pain in the preceding week. It is assessed on a numerical scale of 0 to 10 units. A lower score indicates less pain and a negative change represents an improvement. The Randomized Set consisted of all randomized study participants.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
-1.48
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2 | ||||||||||||
upper limit |
-0.96 |
|
|||||||||||||
End point title |
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) total score at Week 16 | ||||||||||||
End point description |
The Ankylosing Spondylitis Quality of Life (ASQoL), a validated disease-specific 18-item questionnaire, has been developed specifically for measuring health-related quality of life (HRQoL) in participants with ankylosing spondylitis and has shown to be responsive in axial spondyloarthritis (axSpA). Each statement on the ASQoL is given a score of 1=Yes or 0=No. A score of "1" was given where the item was affirmed, indicating adverse quality of life. All item scores were summed to generate the total score ranging from 0 to 18 with a higher score indicating worse health-related quality of life. A negative change from baseline represents an improvement. The Randomized Set consisted of all randomized study participants.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
-1.52
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.36 | ||||||||||||
upper limit |
-0.68 |
|
|||||||||||||
End point title |
Change from Baseline in the Short Form 36-Item Health Survey (SF-36) physical component summary (PCS) score at Week 16 | ||||||||||||
End point description |
SF-36 is a 36-item HRQoL instrument with recall period of 4 weeks. Items are grouped into 8 domains: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items) and 1 item for Health Transition during last year. PCS and Mental Component Summary (MCS) scores are calculated from 8 domains (excluding Health Transition item). Each of SF-36 derived raw scores range from 0 to 100; higher score = better function. PCS score is calculated from 8 domain scores. It is standardized score ranging from 7.3 to 70.1, with mean of 50 and SD of 10 in general US population, higher values = better function, and positive change reflects improvement. PCS score mean below 47 indicates impaired physical functioning. Individual respondent’s score that falls outside T-score range of 45 to 55 are outside average general US population range. Randomized Set was used.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
3.38
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.67 | ||||||||||||
upper limit |
5.09 |
|
|||||||||||||
End point title |
Change from Baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at Week 16 | ||||||||||||
End point description |
The Bath Ankylosing Spondylitis Disease Metrology Index characterizes the spinal mobility of participants with axial Spondyloarthritis (SpA) and Ankylosing Spondylitis. It is a disease-specific measure consisting of 5 clinical measures to reflect participant axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the 5 scores provides the total BASMI score (ranging from 0 to 10). The higher the BASMI score, the more severe the participant's limitation of movement due to their axial SpA. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value, the better the improvement. The Randomized Set consisted of all randomized study participants.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
332
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.006 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
-0.28
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.47 | ||||||||||||
upper limit |
-0.08 |
|
|||||||||||||
End point title |
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the subgroup of participants with enthesitis at Baseline at Week 16 | ||||||||||||
End point description |
The Maastricht Ankylosing Spondylitis Enthesitis is an index that measures the severity (ie, intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous process), each scored as 0 or 1 and then summed for a possible score of 0 to 13. A higher score reflects higher severity and a negative change represents an improvement. Subset of study participants in Randomized Set with enthesitis at Baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.003 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
-1.08
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.79 | ||||||||||||
upper limit |
-0.38 |
|
|||||||||||||
End point title |
Percentage of Participants With Enthesitis-free state at Week 16 based on the Maastricht Ankylosing Spondylitis Enthesitis Index in the subgroup of participants with enthesitis at Baseline | ||||||||||||
End point description |
The Maastricht Ankylosing Spondylitis Enthesitis is an index that measures the severity (ie, intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous process) each scored as 0 or 1 and then summed for a possible score of 0 to 13. Enthesitis free state is defined as having a MASES score of 0. A higher score reflects higher severity and a negative change represents an improvement. Subset of study participants in Randomized Set with enthesitis at Baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo (up to Week 16) v Bimekizumab 160 mg Q4W (up to Week 16)
|
||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.006 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.47
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.3 | ||||||||||||
upper limit |
4.68 |
|
|||||||||||||||||||||
End point title |
Percentage of participants with treatment-emergent adverse events (TEAEs) during the study | ||||||||||||||||||||
End point description |
TEAEs are defined as those AEs that have a start date on or following the first dose of study treatment through the final dose of study treatment + 140 days (covering the 20-week Safety follow up (SFU) period). TEAEs were analyzed and reported for DBTP (Safety set), MP (Maintenance Set) and Overall Period (Safety set) which includes all participants who received BKZ 60 mg Q4W during the study. The Safety Set consisted of all randomized study participants who received at least one dose of the IMP.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) until Safety-Follow-Up (up to Week 68)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study | ||||||||||||||||||||
End point description |
A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulted in 1) Death, 2) Life-threatening (Life-threatening does not include a reaction that might have caused death had it occurred in a more severe form.), 3) Significant or persistent disability/incapacity, 4) Congenital anomaly/birth defect (including that occurring in a fetus), 5) Important medical event that, based upon appropriate medical judgment, may jeopardize the participant or participant may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious (Important medical events may include, but are not limited to, potential Hy’s Law [see allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.) The Safety Set consisted of all randomized study participants who received at least one dose of the IMP.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) until Safety-Follow-Up (up to Week 68)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of participants with treatment-emergent adverse events (TEAEs) leading to withdrawal from investigational medicinal product (IMP) during the study | ||||||||||||||||||||
End point description |
TEAEs are defined as those AEs that have a start date on or following the first dose of study treatment through the final dose of study treatment + 140 days (covering the 20-week SFU period). The Safety Set consisted of all randomized study participants who received at least one dose of the IMP.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) until Safety-Follow-Up (up to Week 68)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
From Baseline (Day 1) until Safety-Follow-Up (up to Week 68)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
As pre-specified in SAP, Maintenance Period (MP) included AEs of SFU for participants who did not enter the open label extension or discontinued early in MP. TEAEs were analyzed and reported for DBTP (Safety set), MP (Maintenance Set) and Overall Period (Safety set) which includes all participants who received BKZ 60 mg Q4W during the study.
|
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Double Blind Treatment Period (up to Week 16): Placebo
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Reporting group description |
Participants received placebo matched to bimekizumab 160 mg Q4W subcutaneously until Week 16. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Period (up to Week 48+20 Weeks SFU):Bimekizumab 160 mg
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Reporting group description |
Participants who received bimekizumab 160 mg Q4W subcutaneously from Day 1 and participants who switched from placebo arm at Week 16 to receive bimekizumab 160 mg Q4W subcutaneously were included in this group. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Maintenance Period (Weeks 16 to 52): Bimekizumab 160 mg
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Reporting group description |
At the end of the 16-week Double-Blind Treatment Period, study participants receiving placebo were re-allocated to bimekizumab treatment at Week 16. All Participants received bimekizumab 160 mg Q4W subcutaneously from Week 16 until Week 48. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Double Blind Treatment Period(up to Week 16):Bimekizumab160 mg
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Reporting group description |
Participants received bimekizumab 160 mg Q4W subcutaneously until Week 16. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Sep 2019 |
Protocol Amendment 1 (11 Sep 2019) implemented changes in response to scientific discussions and feedback provided at meetings with Investigators and advisors or for clarifications. Mainly, imaging assessments were amended with sacroiliac joint and spine MRIs performed at Weeks 16 and 52 for all consenting study participants participating in the MRI substudy regardless of MRI positivity at Baseline. These additional MRIs allowed an exploratory evaluation of any changes in the sacroiliac joints and spine after 16 or 52 weeks in study participants who were MRI-negative at Baseline and on early signals such as the impact on active inflammation at Week 16. Additionally, including MRI-positive and MRI-negative study participants in the substudy was considered a more holistic strategy comparable to the approach used for other
compounds. At the same time, the optional participation in the MRI substudy was expanded to all study participants without restriction. |
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17 Oct 2019 |
Protocol Amendment 2 (17 Oct 2019) implemented an update of Inclusion Criterion to reflect the treatment guidelines for axSpA, as presented in the recent European League Against Rheumatism/ASAS and American College of Rheumatology/Spondyloarthritis Research and
Treatment Network guidelines. In addition, a minor update for consistency was made. |
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16 Feb 2021 |
Protocol Amendment 4 (16 Feb 2021) updated the handling of missing data for the statistical analysis of the primary endpoint in response to an agency request. The COVID-19 Free
Set (CFS) was added in response to industry recommendations for evaluating the impact of the pandemic. In addition, other previously planned supportive analyses defined in the Statistical Analysis Plan (SAP) were added for completeness. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |