Clinical Trial Results:
A Multicenter, Open-Label, Follow-Up Study to Evaluate the Long-Term Safety and Efficacy of Bimekizumab in Subjects with Psoriatic Arthritis
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Summary
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EudraCT number |
2017-001003-74 |
Trial protocol |
HU CZ DE |
Global end of trial date |
29 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Nov 2021
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First version publication date |
12 Nov 2021
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Other versions |
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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 |
PA0009
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03347110 | ||
WHO universal trial number (UTN) |
- | ||
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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 Nov 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Oct 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 |
To Assess the long-term safety and tolerability of bimekizumab administered over a period of up to 2 years.
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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 |
21 Nov 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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: 24
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Poland: 94
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Country: Number of subjects enrolled |
Russian Federation: 13
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Country: Number of subjects enrolled |
United States: 35
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Worldwide total number of subjects |
183
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EEA total number of subjects |
135
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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) |
165
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From 65 to 84 years |
18
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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 November 2017 and concluded in October 2020. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Participant Flow refers to the Safety Set. Participants who completed the study PA0008 (NCT02969525) were eligible to enroll in study PA0009. A total of 184 participants from PA0008 signed the Informed Consent Form and were enrolled in PA0009 study. Among 184 participants, 1 participant did not receive treatment and was not included in analysis. | ||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Bimekizumab 160 mg | ||||||||||||||||||
Arm description |
Participants received bimekizumab (BKZ) 160 milligrams (mg) as a subcutaneous (sc) injection every 4 weeks (Q4W) for up to 100 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
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 Q4W at prespecified time points.
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Baseline characteristics reporting groups
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Reporting group title |
Bimekizumab 160 mg
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Reporting group description |
Participants received bimekizumab (BKZ) 160 milligrams (mg) as a subcutaneous (sc) injection every 4 weeks (Q4W) for up to 100 weeks. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bimekizumab 160 mg
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Reporting group description |
Participants received bimekizumab (BKZ) 160 milligrams (mg) as a subcutaneous (sc) injection every 4 weeks (Q4W) for up to 100 weeks. | ||
Subject analysis set title |
Bimekizumab 160 mg (SS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received BKZ 160 mg as a sc injection Q4W for up to 100 weeks. Participants formed the Safety Set (SS) which consisted of all study participants who had given informed consent for PA0009 and had received at least one dose of study medication in PA0009.
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Subject analysis set title |
Bimekizumab 160 mg (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants received BKZ 160 mg as a sc injection Q4W for up to 100 weeks. Participants formed the Full Analysis Set (FAS) which consisted of all enrolled participants who received at least 1 dose of study medication in PA0009 and had a valid measurement for at least 1 efficacy variable after PA0009 entry visit.
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End point title |
Percentage of Participants With treatment-emergent adverse events (TEAEs) during the study [1] | ||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a participant 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. TEAEs were defined as events with onset date on or after the start date of study medication in PA0009. The Safety Set (SS) consisted of all study participants who had given informed consent for PA0009 and had received at least one dose of study medication in PA0009.
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End point type |
Primary
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End point timeframe |
From Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120)
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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 endpoint. 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 treatment-emergent serious adverse events (SAEs) during the study [2] | ||||||||
End point description |
A serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization. The SS consisted of all study participants who had given informed consent for PA0009 and had received at least one dose of study medication in PA0009.
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End point type |
Primary
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End point timeframe |
From Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120)
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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 endpoint. 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 treatment-emergent adverse event (TEAE) during the study | ||||||||
End point description |
An adverse event (AE) is 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. The SS consisted of all study participants who had given informed consent for PA0009 and had received at least one dose of study medication in PA0009.
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End point type |
Secondary
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End point timeframe |
From Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With American College of Rheumatology 20% Improvement (ACR20) Response at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
The ACR20 response rate was based on 20% or greater improvement relative to Baseline of PA0008 in the following measures: Tender Joint Count (TJC) based on 78 joints, Swollen Joint Count (SJC) based on 76 joints; 3 of the 5 remaining core set measures: Disease activity as assessed by Patient's Global Assessment of Disease Activity (PGADA), Disease activity as assessed by Physician's Global Assessment of Disease Activity (PhGADA), Pain as assessed by Patient's Assessment of Arthritis Pain (PtAAP), Physical function as assessed by Health Assessment Questionnaire - Disability Index (HAQ-DI), Acute phase response as assessed by high sensitivity C-reactive protein (hs CRP). Participants for whom ACR could not be derived due to missing data were counted as non-responders as per NRI analysis. FAS consisted of all enrolled participants who received at least 1 dose of study medication in PA0009 and had a valid measurement for at least 1 efficacy variable after PA0009 entry visit.
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With American College of Rheumatology 50% Improvement (ACR50) Response at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
The ACR50 response rate was based on 50% or greater improvement relative to Baseline of PA0008 in the following measures: TJC based on 78 joints, SJC based on 76 joints; 3 of the 5 remaining core set measures: Disease activity as assessed by PGADA, Disease activity as assessed by PhGADA, Pain as assessed by PtAAP, Physical function as assessed by HAQ-DI, Acute phase response as assessed by hs CRP. Participants for whom ACR could not be derived due to missing data were counted as non-responders as per NRI analysis. FAS consisted of all enrolled participants who received at least 1 dose of study medication in PA0009 and had a valid measurement for at least 1 efficacy variable after PA0009 entry visit.
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With American College of Rheumatology 70% Improvement (ACR70) Response at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
The ACR70 response rate was based on 70% or greater improvement relative to Baseline of PA0008 in the following measures: TJC based on 78 joints, SJC based on 76 joints; 3 of the 5 remaining core set measures: Disease activity as assessed by PGADA, Disease activity as assessed by PhGADA, Pain as assessed by PtAAP, Physical function as assessed by HAQ-DI, Acute phase response as assessed by hs CRP. Participants for whom ACR could not be derived due to missing data were counted as non-responders as per NRI analysis. FAS consisted of all enrolled participants who received at least 1 dose of study medication in PA0009 and had a valid measurement for at least 1 efficacy variable after PA0009 entry visit.
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline of PA0008 in Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
The MASES 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 item was scored as 0 = not tender or 1 = tender and then were summed for a possible score of 0 to 13, with higher scores indicating worse enthesitis. If 7 or more items were available, MASES was calculated by dividing the summed score with the number of assessments and multiplying the result by 13. If less than 7 items were available, MASES was treated as missing. Subset of study participants in the FAS with Enthesitis at PA0008 Baseline (MASES>0).
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline of PA0008 in the Leeds Dactylitis Index (LDI) at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
Presence of dactylitis was assessed using the LDI basic which evaluated for a greater than or equal to (>=) 10% difference in the circumference of the digit compared to the opposite digit and was then multiplied by the tenderness score, using a simple grading system (0=absent, 1=present). The results from each digit with dactylitis were summed to produce a final score. For the final score, the minimum value for LDI is zero and there is no maximum value. A low score indicates less dactylitis symptoms. A score of zero is considered dactylitis free. Observed values have been reported in this outcome measure. Subset of study participants in the FAS with Dactylitis at PA0008 Baseline (LDI>0).
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Psoriasis Area Severity Index (PASI75) Response at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
PASI75 response assessments are based on at least 75% improvement in PASI score from Baseline of PA0008. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining % of skin covered with psoriasis (PSO) for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved PSO area score of the respective section, and weighted by the % of the person’s affected skin for the respective section. Final score between 0=no disease and 72= maximal disease. Missing PASI responses were imputed using LOCF for any visits where the corresponding body surface area (BSA) has not increased compared to the preceding visit. Subset of study participants in FAS with BSA affected by PSO of >=3% at PA0008 Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Psoriasis Area Severity Index (PASI90) Response at Week 48 calculated relative to Baseline of PA0008 | ||||||||
End point description |
The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline of PA0008. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. Final score between 0=no disease and 72= maximal disease. Missing PASI responses were imputed using LOCF for any visits where the corresponding BSA has not increased compared to the preceding visit. Subset of study participants in FAS with BSA affected by PSO of >=3% at PA0008 Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline of PA0008, Week 48
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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 Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120)
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Adverse event reporting additional description |
A TEAE was defined as an event with onset date on or after the start date of study medication in PA0009.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
Bimekizumab 160 mg (SS)
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Reporting group description |
Participants received BKZ 160 mg as a sc injection Q4W for up to a maximum of 100 weeks. Participants formed the SS consisted of all enrolled participants who received at least 1 dose of study medication in PA0009 and had a valid measurement for at least 1 efficacy variable after PA0009 entry visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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09 Mar 2018 |
The purpose of this substantial amendment was the following:
• To update the study contact details for the sponsor study physician and clinical trial biostatistician.
• Amend the open-label treatment period for clarification, as per request from the regulatory agency.
• Amend the study procedures and assessments to be performed at the SFU visit. Efficacy assessments were removed since they were not required at the SFU visit.
• Include additional wording to the inclusion criteria (criterion#5) listing acceptable methods of contraception for female study participants.
• Amend the exclusion criteria (criterion #2) to include further clarification on when to consult the medical monitor.
• To revise the withdrawal criteria section to provide instructions for the management of study participants with newly diagnosed inflammatory bowel disease (IBD) or with IBD flares during the study.
• To revise and clarify the serious adverse event (SAE) criteria for pregnancy for consistency.
• Amend the table for identification/exclusion of alternative etiology to include alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
• Amend and remove wording from the criteria determined for handling of dropouts or missing data. |
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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 | |||
