Clinical Trial Results:
A Multicenter, Phase 2A, Randomized, Investigator-Blind, Subject-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Bimekizumab and Certolizumab Pegol in Subjects With Active Ankylosing Spondylitis
Summary
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EudraCT number |
2017-000957-37 |
Trial protocol |
CZ DE GR NL |
Global end of trial date |
25 May 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Jun 2021
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First version publication date |
10 Jun 2021
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Other versions |
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 |
AS0013
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03215277 | ||
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 |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, 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 |
23 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 May 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
25 May 2020
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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 |
Evaluate the efficacy of bimekizumab compared to certolizumab pegol (CZP) 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 |
Proof of concept study to compare the efficacy and safety of the already market-authorized tumor necrosis factor-α (TNF-alpha) Inhibitor CZP vs the investigational IL17 A/F inhibitor BKZ in the AS-indication. | ||
Actual start date of recruitment |
04 Oct 2017
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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 |
Czechia: 11
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Country: Number of subjects enrolled |
Germany: 10
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Country: Number of subjects enrolled |
Greece: 6
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Country: Number of subjects enrolled |
Moldova, Republic of: 7
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Poland: 31
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Country: Number of subjects enrolled |
Russian Federation: 9
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
76
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EEA total number of subjects |
59
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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) |
72
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From 65 to 84 years |
4
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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 October 2017 and concluded in May 2020. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
The Participant Flow refers to the Randomized Set (RS). | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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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, Assessor, Carer | ||||||||||||||||||||||||
Blinding implementation details |
This is an investigator-blind and subject-blind study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Certolizumab pegol | ||||||||||||||||||||||||
Arm description |
Participants received certolizumab pegol (CZP) 400 milligrams (mg) subcutaneously (sc) every 2 weeks (Q2W) at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg sc Q2W in Weeks 6 to 10 and 400 mg every 4 weeks (Q4W) from Week 12 to Week 44. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Certolizumab Pegol
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Investigational medicinal product code |
CDP870
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Other name |
CZP, Cimzia
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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 CZP 400 mg Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg Q2W in Weeks 6 to 10 and 400 mg Q4W from Week 12 to Week 44.
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Arm title
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Bimekizumab | ||||||||||||||||||||||||
Arm description |
Participants received bimekizumab (BKZ) 160 mg sc Q2W from Week 0 through Week 10 and 320 mg sc Q4W from Week 12 to Week 44. In addition, participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
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
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4.
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Investigational medicinal product name |
Bimekizumab
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Investigational medicinal product code |
UCB4940
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Other name |
BKZ
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received BKZ 160 mg Q2W from Week 0 through Week 10 and 320 mg Q4W from Week 12 to Week 44.
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Baseline characteristics reporting groups
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Reporting group title |
Certolizumab pegol
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Reporting group description |
Participants received certolizumab pegol (CZP) 400 milligrams (mg) subcutaneously (sc) every 2 weeks (Q2W) at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg sc Q2W in Weeks 6 to 10 and 400 mg every 4 weeks (Q4W) from Week 12 to Week 44. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bimekizumab
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Reporting group description |
Participants received bimekizumab (BKZ) 160 mg sc Q2W from Week 0 through Week 10 and 320 mg sc Q4W from Week 12 to Week 44. In addition, participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Certolizumab pegol
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Reporting group description |
Participants received certolizumab pegol (CZP) 400 milligrams (mg) subcutaneously (sc) every 2 weeks (Q2W) at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg sc Q2W in Weeks 6 to 10 and 400 mg every 4 weeks (Q4W) from Week 12 to Week 44. | ||
Reporting group title |
Bimekizumab
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Reporting group description |
Participants received bimekizumab (BKZ) 160 mg sc Q2W from Week 0 through Week 10 and 320 mg sc Q4W from Week 12 to Week 44. In addition, participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4. | ||
Subject analysis set title |
Certolizumab pegol (SS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received CZP 400 mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg sc Q2W in Weeks 6 to 10 and 400 mg Q4W from Week 12 to Week 44. Participants formed the Safety Set (SS).
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Subject analysis set title |
Bimekizumab (SS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received BKZ 160 mg sc Q2W from Week 0 through Week 10 and 320 mg sc Q4W from Week 12 to Week 44. In addition, participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4. Participants formed the SS.
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Subject analysis set title |
Certolizumab pegol (PPS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants received CZP 400 mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg sc Q2W in Weeks 6 to 10 and 400 mg Q4W from Week 12 to Week 44. Participants formed the Per Protocol Set (PPS).
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Subject analysis set title |
Bimekizumab (PPS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants received BKZ 160 mg sc Q2W from Week 0 through Week 10 and 320 mg sc Q4W from Week 12 to Week 44. In addition, participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4. Participants formed the PPS.
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End point title |
Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12 | ||||||||||||
End point description |
ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP [mg/L] + 1). Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. Posterior means and 95% credible intervals in each group are presented. PPS consisted of all study participants in the FAS who had no important protocol deviation affecting the primary efficacy variable. N signifies participants evaluable.
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End point type |
Primary
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End point timeframe |
From Baseline to Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Results were based on a complete case (ie, data as observed) Bayesian linear model with the change from Baseline in ASDAS as the independent variable. Treatment was included as a predictor in the model and Baseline ASDAS as a covariate. The mean posterior difference and 95% credible interval were presented for the BKZ vs CZP comparison.
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Comparison groups |
Certolizumab pegol (PPS) v Bimekizumab (PPS)
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean Posterior Difference | ||||||||||||
Point estimate |
0.23
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.14 | ||||||||||||
upper limit |
0.6 | ||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||
Statistical analysis description |
Results were based on a complete case (ie, data as observed) Bayesian linear model with the change from Baseline in ASDAS as the independent variable. Treatment was included as a predictor in the model and Baseline ASDAS as a covariate. Pr[Diff>0%](%) refers to the probability that the mean change from Baseline in ASDAS in the BKZ group was greater than the mean change from Baseline in ASDAS in the CZP group. 0% Confidence Interval (CI) [0,999] was used a placeholder.
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Comparison groups |
Certolizumab pegol (PPS) v Bimekizumab (PPS)
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
PR[Diff > 0%](%) | ||||||||||||
Point estimate |
88.4
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Confidence interval |
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level |
0% | ||||||||||||
sides |
2-sided
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lower limit |
0 | ||||||||||||
upper limit |
999 |
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End point title |
Percentage of participants with adverse events (AE) during the study conduct [1] | ||||||||||||
End point description |
An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A treatment-emergent adverse event (TEAE) was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP. Safety Set (SS) consisted of all randomized study participants who received at least 1 dose (full or partial) of the IMP.
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End point type |
Primary
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End point timeframe |
From Baseline until Safety Follow-Up Visit (up to Week 64)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
Percentage of participants with serious adverse events (SAEs) during the study conduct [2] | ||||||||||||
End point description |
An SAE was any untoward medical occurrence that at any dose:
- Resulted in death
- Is life-threatening
- Required in patient hospitalisation or prolongation of existing hospitalisation
- Is a congenital anomaly or birth defect
- Is an infection that requires treatment with parenteral antibiotics
- Other important medical events which based on medical or scientific judgement may jeopardised the participants, or may require medical or surgical intervention to prevent any of the above. A TEAE was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP. Safety Set (SS) consisted of all randomized study participants who received at least 1 dose (full or partial) of the IMP.
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End point type |
Primary
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End point timeframe |
From Baseline until Safety Follow-Up Visit (up to Week 64)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
Percentage of participants who withdrew due to an adverse event (AE) during the study conduct [3] | ||||||||||||
End point description |
An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP. Safety Set (SS) consisted of all randomized study participants who received at least 1 dose (full or partial) of the IMP.
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End point type |
Primary
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End point timeframe |
From Baseline until Safety Follow-Up Visit (up to Week 64)
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
Percentage of participants with Ankylosing Spondylitis Disease Activity Score - Inactive Disease (ASDAS-ID) at Week 12 | ||||||||||||
End point description |
ASDAS-ID was defined by ASDAS < 1.3. ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP [mg/L] + 1). Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score. Per-Protocol Set (PPS) consisted of all study participants in the Full Analysis Set (FAS) who had no important protocol deviation affecting the primary efficacy variable. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Week 12
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No statistical analyses for this end point |
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End point title |
Percentage of participants with Ankylosing Spondylitis Disease Activity Score-Major Improvement (ASDAS-MI) at Week 12 | ||||||||||||
End point description |
ASDAS-MI was defined by a reduction (improvement) from Baseline in ASDAS >=2 units. ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP [mg/L] + 1). Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score. PPS consisted of all study participants in the Full Analysis Set who had no important protocol deviation affecting the primary efficacy variable. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline until Safety Follow-Up Visit (up to Week 64)
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Adverse event reporting additional description |
A treatment-emergent adverse event (TEAE) was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.
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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 |
Certolizumab pegol (SS)
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Reporting group description |
Participants received CZP 400 mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed by CZP 200 mg sc Q2W in Weeks 6 to 10 and 400 mg Q4W from Week 12 to Week 44. Participants formed the Safety Set (SS). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bimekizumab (SS)
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Reporting group description |
Participants received BKZ 160 mg sc Q2W from Week 0 through Week 10 and 320 mg sc Q4W from Week 12 to Week 44. In addition, participants received placebo injection to maintain the blind for the CZP loading dose at Baseline, Week 2 and Week 4. Participants formed the SS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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05 Mar 2018 |
The substantial Protocol Amendment 2 included the following key updates:
• Withdrawal criteria section to provide instructions for the management of study participants with newly diagnosed inflammatory bowel disease or with inflammatory bowel disease flares during the study.
• Statistical analysis section of the protocol, text describing the planned analysis of the primary efficacy variable, and text describing the planned interim analyses and sample size re-estimation. The rationale for this was that the observed pattern of study participant recruitment was not as expected at the time of study planning. |
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27 Feb 2019 |
The substantial Protocol Amendment 3 included the following key updates:
• Secondary and other study objectives and variables were updated to evaluate the effect of bimekizumab or certolizumab pegol on changes in bone formation as exploratory.
• Objectives related to pharmacokinetic and immunogenicity were updated to other objectives for consistency with the classification of the corresponding variables.
• Nonhereditary pharmacogenomic variables and pharmacogenetic variables were updated as exploratory.
• A Prefilled syringe (PFS) was available for administration in addition to the vial and corresponding text was added.
• An informal unblinded interim analysis when the last randomized study participant had completed the Week 12 Visit was added to facilitate clinical planning. |
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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 |