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

Ankylosing Spondylitis Clinical Trial

— BE AGILE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02963506
• Other study ID #: AS0008
• Secondary ID: 2016-001102-42
• Status: Completed
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: August 2018

Study information

• Verified date: May 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: August 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. BASDAI score >=4

2. 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:

1. inadequate response to nonsteroidal anti-inflammatory drug (NSAID) therapy

2. intolerance to administration of at least 1 NSAID

3. 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:

1. experienced an inadequate response to previous treatment given for at least 12 weeks

2. been intolerant to administration (eg, had a side effect/adverse event that led to discontinuation)

3. 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:

1. <= 3 excised or ablated basal cell carcinomas of the skin

2. 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

3. Actinic keratosis (-es)

4. Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Other:
• Placebo

Drug:
• Bimekizumab
Bimekizumab in different dosages.

Locations

Country	Name	City	State
Bulgaria	As0008 156	Dobrich
Bulgaria	As0008 151	Plovdiv
Bulgaria	As0008 154	Plovdiv
Bulgaria	As0008 155	Plovdiv
Bulgaria	As0008 150	Ruse
Canada	As0008 101	Quebec
Canada	As0008 100	Victoria
Canada	As0008 103	Winnipeg
Czechia	As0008 205	Brno
Czechia	As0008 206	Hustopece
Czechia	As0008 207	Olomouc
Czechia	As0008 208	Pardubice
Czechia	As0008 211	Praha
Czechia	As0008 210	Praha 11
Czechia	As0008 202	Praha 2
Czechia	As0008 201	Praha 4
Czechia	As0008 209	Praha 4
Czechia	As0008 203	Zlín
Germany	As0008 302	Cologne
Germany	As0008 304	Hamburg
Germany	As0008 308	Hannover
Germany	As0008 303	Herne
Germany	As0008 301	Ratingen
Hungary	As0008 400	Budapest
Hungary	As0008 403	Budapest
Hungary	As0008 402	Debrecen
Hungary	As0008 401	Veszprem
Poland	As0008 466	Bydgoszcz
Poland	As0008 453	Elblag
Poland	As0008 456	Elblag
Poland	As0008 455	Krakow
Poland	As0008 461	Lublin
Poland	As0008 467	Nowa Sol
Poland	As0008 451	Poznan
Poland	As0008 462	Poznan
Poland	As0008 450	Torun
Poland	As0008 454	Warszawa
Poland	As0008 459	Warszawa
Poland	As0008 457	Wroclaw
Poland	As0008 460	Wroclaw
Poland	As0008 465	Wroclaw
Russian Federation	As0008 601	Moscow
Russian Federation	As0008 604	Moscow
Russian Federation	As0008 605	Moscow
Russian Federation	As0008 607	Moscow
Russian Federation	As0008 600	Saint Petersburg
Russian Federation	As0008 606	Saint Petersburg
Russian Federation	As0008 608	Saint Petersburg
Russian Federation	As0008 609	Saint Petersburg
Russian Federation	As0008 610	Saint Petersburg
Spain	As0008 800	Cordoba
Spain	As0008 801	La Coruna
Spain	As0008 803	Santiago de Compostela
Ukraine	As0008 700	Kiev
Ukraine	As0008 707	Kyiv
Ukraine	As0008 705	Ternopil
Ukraine	As0008 708	Uzhgorod
Ukraine	As0008 706	Vinnytsya
Ukraine	As0008 704	Zaporizhya
United States	As0008 019	Anniston	Alabama
United States	As0008 020	Austin	Texas
United States	As0008 005	Aventura	Florida
United States	As0008 027	Boston	Massachusetts
United States	As0008 015	Cleveland	Ohio
United States	As0008 006	Dallas	Texas
United States	As0008 001	Duncansville	Pennsylvania
United States	As0008 021	Freehold	New Jersey
United States	As0008 018	Houston	Texas
United States	As0008 007	La Jolla	California
United States	As0008 022	Ormond Beach	Florida
United States	As0008 014	Portland	Oregon
United States	As0008 030	Sarasota	Florida
United States	As0008 002	Seattle	Washington
United States	As0008 009	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Germany,  Hungary,  Poland,  Russian Federation,  Spain,  Ukraine, 

References & Publications (2)

Robinson PC, Machado PM, Haroon N, Gensler LS, Reveille JD, Taieb V, Vaux T, Fleurinck C, Oortgiesen M, de Peyrecave N, Deodhar A. Minimal Impact of the COVID-19 Pandemic on Disease Activity and Health-Related Quality of Life in Patients With Ankylosing S — View Citation

van der Heijde D, Gensler LS, Deodhar A, Baraliakos X, Poddubnyy D, Kivitz A, Farmer MK, Baeten D, Goldammer N, Coarse J, Oortgiesen M, Dougados M. Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylos — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)