A Study to Evaluate the Efficacy and Safety of Different Doses of Bimekizumab in Subjects With Active Ankylosing Spondylitis

Study Overview
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Brief Summary
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This is a study to evaluate the efficacy and safety of different doses of bimekizumab in subjects with active Ankylosing Spondylitis (AS).

Official Title
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A Multicenter, Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of Bimekizumab in Subjects With Active Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Other: Placebo
* Drug: Bimekizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has active ankylosing spondylitis (AS), determined by documented radiologic evidence fulfilling the Modified New York criteria for AS including symptoms for >=3 months and age of onset <45 years Subject has moderate to severe active disease as defined by each of the following: BASDAI score >=4 Spinal pain >=4 on a 0 to 10 NRS (Numeric Rating Scale; from BASDAI item 2) Subjects must have at least 1 of the following: inadequate response to nonsteroidal anti-inflammatory drug (NSAID) therapy intolerance to administration of at least 1 NSAID contraindication(s) to NSAID therapy Subjects who are regularly taking NSAIDs/COX-2 inhibitors as part of their AS therapy are required to be on a stable dose for at least 14 days before Baseline Subjects taking corticosteroids must be on an average daily dose of <=10mg/day prednisone or equivalent for at least 14 days before Baseline and should remain on a stable dose up to Week 16 Subjects taking methotrexate (MTX) (<=25mg/week) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization Subjects taking sulfasalazine (up to 3grams/day) or hydroxychloroquine (up to 400mg per day total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization Subjects may be tumor necrosis factor (TNF) inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects who have been on a TNF inhibitor previously must have: experienced an inadequate response to previous treatment given for at least 12 weeks been intolerant to administration (eg, had a side effect/adverse event that led to discontinuation) lost access to TNF inhibitor for other reasons Exclusion Criteria: Subjects with a total ankylosis of the spine, or a diagnosis of any other inflammatory arthritis eg, rheumatoid arthritis (RA), sarcoidosis, systemic lupus erythematosus, or reactive arthritis Subjects with any current sign or symptom that may indicate an active infection (except for the common cold) Subjects with a history of chronic or recurrent infections, or a serious or life-threatening infection within the 6 months prior to the Baseline Visit Subjects receiving any live vaccination within the 8 weeks prior to Baseline Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, with latent TB infection or current or history of nontuberculous mycobacteria (NTMB) infection Subjects with concurrent malignancy or a history of malignancy during the past 5 years will be excluded, with following exceptions that may be included: <= 3 excised or ablated basal cell carcinomas of the skin One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening Actinic keratosis (-es) Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will receive for 12 Weeks Placebo and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks. | Other: Placebo<br> <br> |
| Experimental: Bimekizumab Dose 1<br>Subjects will receive for 12 Weeks Bimekizumab Dose 1 and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks. | Drug: Bimekizumab<br>* Bimekizumab in different dosages.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab Dose 2<br>Subjects will receive for 12 Weeks Bimekizumab Dose 2 and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks. | Drug: Bimekizumab<br>* Bimekizumab in different dosages.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab Dose 3<br>Subjects will receive for 48 Weeks Bimekizumab Dose 3. | Drug: Bimekizumab<br>* Bimekizumab in different dosages.<br>* Other names: UCB4940;|
| Experimental: Bimekizumab Dose 4<br>Subjects will receive for 48 Weeks Bimekizumab Dose 4. | Drug: Bimekizumab<br>* Bimekizumab in different dosages.<br>* Other names: UCB4940;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Axial Spondyloarthritis International Society 40% Response Criteria (ASAS40) at Week 12 | The ASAS40 response was defined as relative improvements of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is not active and 10 is very active in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS score), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Note: Participants with missing data or who discontinue study treatment prior to Week 12 were counted as non-responders. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein (ASDAS [CRP]) at Week 12 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI question 2 result) 0.058 x Duration of morning stiffness (BASDAI question 6 result) 0.110 x PGADA 0.073 x Peripheral pain/swelling (BASDAI question 3 result) 0.579 x (natural logarithm of the (hs-CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score since CRP does not have a set upper limit. If one component for the ASDAS-CRP was missing at a given visit, that component was imputed by carrying the last observation forward, and the ASDAS-CRP was calculated accordingly. If the hs-CRP value was below 2 mg/L, then it was imputed as the constant value of 2 mg/L. | From Baseline to Week 12 | 
| Percentage of Participants With Axial Spondyloarthritis International Society 20% Response Criteria (ASAS20) at Week 12 | The ASAS20 response was defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a 0 to 10 NRS, where 0 is not active and 10 is very active in at least 3 of the 4 domains: PGADA, Pain assessment (total spinal pain NRS scores), Function (BASFI), Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20% and an absolute worsening of at least 1 unit]. Note: Participants with missing data or who discontinue study treatment prior to Week 12 were counted as non-responders. | Week 12 | 
| Percentage of Participants With Axial Spondyloarthritis International Society (ASAS) 5/6 Response at Week 12 | The ASAS 5/6 response was defined as at least 20% improvement in at least 5 of the 6 domains: PGADA, Pain assessment (total spinal pain NRS scores), Function (BASFI), Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration), spinal mobility (lateral spinal flexion) and high sensitivity C-reactive protein (hs-CRP). Note: Participants with missing data or who discontinue study treatment prior to Week 12 were counted as non-responders. | Week 12 | 
| Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | The BASDAI is a validated self-reported instrument, which consists of six 10-unit horizontal Numeric Rating Scales (NRS) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. Note: Missing data was imputed using multiple imputation based on the Markov-Chain Monte Carlo method for the intermittent missing data, followed by monotone regression for the monotone missing data assuming missing at random. | From Baseline to Week 12 | 
| Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. Note: Missing data was imputed using multiple imputation based on the Markov-Chain Monte Carlo method for the intermittent missing data, followed by monotone regression for the monotone missing data assuming missing at random. | From Baseline to Week 12 | 
| Percentage of Participants With at Least One Adverse Event (AE) During the Study | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can 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. | From Screening until Safety Follow-Up Visit (up to Week 77) | 
| Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study | A serious adverse event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Is a congenital anomaly or birth defect Is an infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above. | From Screening until Safety Follow-Up Visit (up to Week 77) | 
| Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study | An AE is any untoward medical occurrence in a participant or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Secondary Outcome Measure were summarized from the adverse event pages of the Case Report Forms. | From Screening until Safety Follow-Up Visit (up to Week 77) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AS, Ankylosing Spondylitis, Bimekizumab