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

Phase 2

Completed

• Conditions: Ankylosing Spondylitis
• Interventions: Other: Placebo; Drug: Bimekizumab

• Registration Number: NCT02963506
• Lead Sponsor: UCB Biopharma S.P.R.L.

Brief Summary

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

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-11-10
• Study First Submitted QC: 2016-11-14
• Study First Posted: 2016-11-15
• Primary Completion: 2017-10
• Study Completion: 2018-08
• Disposition First Submitted: 2018-10-22
• Disposition First Submitted QC: 2018-10-22
• Disposition First Posted: 2018-10-23
• Results First Submitted: 2020-10-21
• Results First Submitted QC: 2020-10-21
• Results First Posted: 2020-11-16
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 303

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will receive for 12 Weeks Placebo and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks.
Bimekizumab Dose 2	Bimekizumab	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.
Bimekizumab Dose 1	Bimekizumab	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.
Bimekizumab Dose 3	Bimekizumab	Subjects will receive for 48 Weeks Bimekizumab Dose 3.
Bimekizumab Dose 4	Bimekizumab	Subjects will receive for 48 Weeks Bimekizumab Dose 4.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Axial Spondyloarthritis International Society 40% Response Criteria (ASAS40) at Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein (ASDAS [CRP]) at Week 12	From Baseline to 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.
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)	From Baseline to Week 12	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.
Percentage of Participants With Axial Spondyloarthritis International Society 20% Response Criteria (ASAS20) at Week 12	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.
Percentage of Participants With Axial Spondyloarthritis International Society (ASAS) 5/6 Response at Week 12	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.
Percentage of Participants With at Least One Adverse Event (AE) During the Study	From Screening until Safety Follow-Up Visit (up to Week 77)	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.
Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study	From Screening until Safety Follow-Up Visit (up to Week 77)	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.
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)	From Baseline to Week 12	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.
Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study	From Screening until Safety Follow-Up Visit (up to Week 77)	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.

Trial Locations

Locations (74)

As0008 027; 🇺🇸 Boston, Massachusetts, United States

As0008 154; 🇧🇬 Plovdiv, Bulgaria

As0008 601; 🇷🇺 Moscow, Russian Federation

As0008 403; 🇭🇺 Budapest, Hungary

As0008 303; 🇩🇪 Herne, Germany

As0008 401; 🇭🇺 Veszprem, Hungary

As0008 301; 🇩🇪 Ratingen, Germany

As0008 604; 🇷🇺 Moscow, Russian Federation

As0008 015; 🇺🇸 Cleveland, Ohio, United States

As0008 014; 🇺🇸 Portland, Oregon, United States

As0008 002; 🇺🇸 Seattle, Washington, United States

As0008 456; 🇵🇱 Elblag, Poland

As0008 461; 🇵🇱 Lublin, Poland

As0008 019; 🇺🇸 Anniston, Alabama, United States

As0008 005; 🇺🇸 Aventura, Florida, United States

As0008 009; 🇺🇸 Upland, California, United States

As0008 007; 🇺🇸 La Jolla, California, United States

As0008 022; 🇺🇸 Ormond Beach, Florida, United States

As0008 001; 🇺🇸 Duncansville, Pennsylvania, United States

As0008 030; 🇺🇸 Sarasota, Florida, United States

As0008 021; 🇺🇸 Freehold, New Jersey, United States

As0008 020; 🇺🇸 Austin, Texas, United States

As0008 156; 🇧🇬 Dobrich, Bulgaria

As0008 018; 🇺🇸 Houston, Texas, United States

As0008 155; 🇧🇬 Plovdiv, Bulgaria

As0008 006; 🇺🇸 Dallas, Texas, United States

As0008 150; 🇧🇬 Ruse, Bulgaria

As0008 100; 🇨🇦 Victoria, Canada

As0008 101; 🇨🇦 Quebec, Canada

As0008 151; 🇧🇬 Plovdiv, Bulgaria

As0008 203; 🇨🇿 Zlín, Czechia

As0008 206; 🇨🇿 Hustopece, Czechia

As0008 205; 🇨🇿 Brno, Czechia

As0008 103; 🇨🇦 Winnipeg, Canada

As0008 207; 🇨🇿 Olomouc, Czechia

As0008 210; 🇨🇿 Praha 11, Czechia

As0008 201; 🇨🇿 Praha 4, Czechia

As0008 208; 🇨🇿 Pardubice, Czechia

As0008 202; 🇨🇿 Praha 2, Czechia

As0008 304; 🇩🇪 Hamburg, Germany

As0008 209; 🇨🇿 Praha 4, Czechia

As0008 302; 🇩🇪 Cologne, Germany

As0008 211; 🇨🇿 Praha, Czechia

As0008 308; 🇩🇪 Hannover, Germany

As0008 400; 🇭🇺 Budapest, Hungary

As0008 402; 🇭🇺 Debrecen, Hungary

As0008 466; 🇵🇱 Bydgoszcz, Poland

As0008 455; 🇵🇱 Krakow, Poland

As0008 451; 🇵🇱 Poznan, Poland

As0008 453; 🇵🇱 Elblag, Poland

As0008 467; 🇵🇱 Nowa Sol, Poland

As0008 462; 🇵🇱 Poznan, Poland

As0008 460; 🇵🇱 Wroclaw, Poland

As0008 450; 🇵🇱 Torun, Poland

As0008 454; 🇵🇱 Warszawa, Poland

As0008 459; 🇵🇱 Warszawa, Poland

As0008 457; 🇵🇱 Wroclaw, Poland

As0008 465; 🇵🇱 Wroclaw, Poland

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 800; 🇪🇸 Cordoba, Spain

As0008 801; 🇪🇸 La Coruna, Spain

As0008 610; 🇷🇺 Saint Petersburg, Russian Federation

As0008 700; 🇺🇦 Kiev, Ukraine

As0008 803; 🇪🇸 Santiago de Compostela, Spain

As0008 706; 🇺🇦 Vinnytsya, Ukraine

As0008 705; 🇺🇦 Ternopil, Ukraine

As0008 707; 🇺🇦 Kyiv, Ukraine

As0008 704; 🇺🇦 Zaporizhya, Ukraine

As0008 708; 🇺🇦 Uzhgorod, Ukraine