Clinical trial NCT03928704: A Study to Evaluate the Efficacy and Safety of Bimekizumab in Subjects With Active Nonradiographic Axial Spondyloarthritis
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Bimekizumab in Subjects With Active Nonradiographic Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nonradiographic Axial Spondyloarthritis
Keywords: Nonradiographic axial spondyloarthritis
Axial spondyloarthritis
Nr-axSpA
Bimekizumab
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-04-26
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to demonstrate the efficacy, safety and tolerability of bimekizumab administered subcutaneously (sc) compared to placebo in the treatment of subjects with active nonradiographic axial spondyloarthritis (nr-axSpA).


Eligibility criteria: Inclusion Criteria:

* Male or female patients at least 18 years of age
* Patient has nonradiographic axial spondyloarthritis (nr-axSpA) with all of the following criteria:

  1. Adult-onset axial spondyloarthritis meeting Assessment of SpondyloArthritis International Society (ASAS) classification criteria
  2. Inflammatory back pain for at least 3 months
  3. Age at symptom onset of less than 45 years
  4. NO sacroiliitis (in Anterior-Posterior pelvis or sacroiliac x-ray)
* Active disease defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) \>=4 AND spinal pain \>=4 on a 0 to 10 Numeric Rating Scale
* Objective inflammation defined by sacroiliitis on magnetic resonance imaging and/or elevated C-reactive protein
* Subjects had to have either failed to respond to 2 different nonsteroidal anti-inflammatory drugs (NSAIDs) given at the maximum tolerated dose for a total of 4 weeks or have a history of intolerance to or a contraindication to NSAID therapy
* Patients who have taken a tumor necrosis factor alpha (TNFα) inhibitor must have experienced an inadequate response or intolerance to treatment given at an approved dose for at least 12 weeks
* Patients currently taking NSAIDs, cyclooxygenase 2 (COX-2) inhibitors, analgesics, corticosteroids, methotrexate (MTX), leflunomide (LEF), sulfasalazine (SSZ), hydroxychloroquine (HCQ) AND/OR apremilast can be allowed if they fulfill specific requirements prior to study entry

Exclusion Criteria:

* Treatment with more than 1 TNFα inhibitor and/or more than 2 additional non-TNFα biological response modifiers, or any interleukin (IL)-17 biological response modifier
* Active infection or history of recent serious infections
* Viral hepatitis B or C or human immunodeficiency virus (HIV) infection
* Any live (includes attenuated) vaccination within the 8 weeks prior to entering the study or TB (Bacillus Calmette-Guerin) vaccination within 1 year prior entering the study
* Known tuberculosis (TB) infection, at high risk of acquiring TB infection, or current or history of nontuberculous mycobacterium (NTMB) infection
* Subject has any active malignancy or history of malignancy within 5 years prior to the Screening Visit EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma or in situ cervical cancer
* Diagnosis of inflammatory conditions other than axial spondyloarthritis (axSpA), including but not limited to psoriatic arthritis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, and reactive arthritis. Patients with a diagnosis of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease (IBD) are allowed as long as they have no active symptomatic disease when entering the study
* Presence of active suicidal ideation, or moderately severe major depression or severe major depression
* Female patients who are breastfeeding, pregnant, or planning to become pregnant during the study
* Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening

Primary outcomes:
measure: Percentage of Participants With Assessment of SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants With Assessment of SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response in TNFα Inhibitor-naïve Subjects at Week 16
timeFrame: Week 16
measure: Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants With Assessment of SpondyloArthritis International Society 20% Response Criteria (ASAS20) Response at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) Partial Remission (PR) at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 5/6 Response at Week 16
timeFrame: Week 16
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Nocturnal Spinal Pain Score Using Numeric Rating Scale (NRS) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Total Score at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Short Form 36-Item Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the Subgroup of Participants With Enthesitis at Baseline at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants With Enthesitis-free State at Week 16 Based on the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the Subgroup of Participants With Enthesitis at Baseline
timeFrame: Baseline, Week 16
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study
timeFrame: From Baseline (Day 1) until Safety-Follow-Up (up to Week 68) (Week 48 last IMP intake + 20 weeks SFU)
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Study
timeFrame: From Baseline (Day 1) until Safety Follow-Up (up to Week 68)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study
timeFrame: From Baseline (Day 1) until Safety-Follow-Up (up to Week 68)
Other outcomes:
Locations:
city: Mesa
country: United States
facility: As0010 50131
state: Arizona
city: Phoenix
country: United States
facility: As0010 50052
state: Arizona
city: Sun City
country: United States
facility: As0010 50062
state: Arizona
city: Upland
country: United States
facility: As0010 50060
state: California
city: Ormond Beach
country: United States
facility: As0010 50059
state: Florida
city: Sarasota
country: United States
facility: As0010 50056
state: Florida
city: Hagerstown
country: United States
facility: As0010 50015
state: Maryland
city: Saint Louis
country: United States
facility: As0010 50016
state: Missouri
city: Portland
country: United States
facility: As0010 50055
state: Oregon
city: Duncansville
country: United States
facility: As0010 50020
state: Pennsylvania
city: Memphis
country: United States
facility: As0010 50012
state: Tennessee
city: Dallas
country: United States
facility: As0010 50057
state: Texas
city: Mesquite
country: United States
facility: As0010 50036
state: Texas
city: Spokane
country: United States
facility: As0010 50061
state: Washington
city: Bruxelles
country: Belgium
facility: As0010 40004
city: Genk
country: Belgium
facility: As0010 40003
city: Gent
country: Belgium
facility: As0010 40001
city: Merksem
country: Belgium
facility: As0010 40002
city: Plovdiv
country: Bulgaria
facility: As0010 40006
city: Plovdiv
country: Bulgaria
facility: As0010 40007
city: Sofia
country: Bulgaria
facility: As0010 40005
city: Sofia
country: Bulgaria
facility: As0010 40008
city: Beijing
country: China
facility: As0010 20040
city: Chengdu
country: China
facility: As0010 20021
city: Guangzhou
country: China
facility: As0010 20019
city: Hefei
country: China
facility: As0010 20034
city: Nanjing
country: China
facility: As0010 20024
city: Shanghai
country: China
facility: As0010 20018
city: Shanghai
country: China
facility: As0010 20020
city: Shanghai
country: China
facility: As0010 20026
city: Wenzhou
country: China
facility: As0010 20025
city: Brno
country: Czechia
facility: As0010 40011
city: Pardubice
country: Czechia
facility: As0010 40009
city: Praha 11
country: Czechia
facility: As0010 40013
city: Praha 2
country: Czechia
facility: As0010 40016
city: Praha 4
country: Czechia
facility: As0010 40014
city: Praha
country: Czechia
facility: As0010 40015
city: Uherske Hradiste
country: Czechia
facility: As0010 40010
city: Zlin
country: Czechia
facility: As0010 40012
city: Boulogne Billancourt
country: France
facility: As0010 40018
city: Limoges
country: France
facility: As0010 40022
city: Berlin
country: Germany
facility: As0010 40025
city: Hamburg
country: Germany
facility: As0010 40029
city: Hanover
country: Germany
facility: As0010 40024
city: Herne
country: Germany
facility: As0010 40027
city: Leipzig
country: Germany
facility: As0010 40078
city: Ratingen
country: Germany
facility: As0010 40026
city: Debrecen
country: Hungary
facility: As0010 40032
city: Szeged
country: Hungary
facility: As0010 40031
city: Szombathely
country: Hungary
facility: As0010 40080
city: Székesfehérvár
country: Hungary
facility: As0010 40033
city: Chuo-ku
country: Japan
facility: As0010 20030
city: Iruma-gun
country: Japan
facility: As0010 20039
city: Kawachinagano
country: Japan
facility: As0010 20036
city: Kita-gun
country: Japan
facility: As0010 20045
city: Kitakyushu
country: Japan
facility: As0010 20065
city: Nankoku-shi
country: Japan
facility: As0010 20038
city: Osaka
country: Japan
facility: As0010 20037
city: Saga
country: Japan
facility: As0010 20084
city: Saitama
country: Japan
facility: As0010 20048
city: Sapporo
country: Japan
facility: As0010 20031
city: Tokyo
country: Japan
facility: As0010 20035
city: Elblag
country: Poland
facility: As0010 40038
city: Krakow
country: Poland
facility: As0010 40042
city: Lublin
country: Poland
facility: As0010 40037
city: Poznan
country: Poland
facility: As0010 40044
city: Torun
country: Poland
facility: As0010 40040
city: Warszawa
country: Poland
facility: As0010 40041
city: Wroclaw
country: Poland
facility: As0010 40039
city: Wroclaw
country: Poland
facility: As0010 40043
city: A Coruna
country: Spain
facility: As0010 40045
city: Cordoba
country: Spain
facility: As0010 40046
city: Madrid
country: Spain
facility: As0010 40047
city: Santiago de Compostela
country: Spain
facility: As0010 40048
city: Sevilla
country: Spain
facility: As0010 40049
city: Ankara
country: Turkey
facility: As0010 40052
city: Ankara
country: Turkey
facility: As0010 40053
city: Istanbul
country: Turkey
facility: As0010 40050
city: Izmir
country: Turkey
facility: As0010 40051
city: Edinburgh
country: United Kingdom
facility: As0010 40057
city: Leeds
country: United Kingdom
facility: As0010 40056
city: London
country: United Kingdom
facility: As0010 40054
city: Norwich
country: United Kingdom
facility: As0010 40055
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: van der Heijde D, Deodhar A, Baraliakos X, Brown MA, Dobashi H, Dougados M, Elewaut D, Ellis AM, Fleurinck C, Gaffney K, Gensler LS, Haroon N, Magrey M, Maksymowych WP, Marten A, Massow U, Oortgiesen M, Poddubnyy D, Rudwaleit M, Shepherd-Smith J, Tomita T, Van den Bosch F, Vaux T, Xu H. Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials. Ann Rheum Dis. 2023 Apr;82(4):515-526. doi: 10.1136/ard-2022-223595. Epub 2023 Jan 17.
citation: Navarro-Compan V, Ramiro S, Deodhar A, Mease PJ, Rudwaleit M, de la Loge C, Fleurinck C, Taieb V, Morup MF, Massow U, Kay J, Magrey M. Association of clinical response criteria and disease activity levels with axial spondyloarthritis core domains: results from two phase 3 randomised studies, BE MOBILE 1 and 2. RMD Open. 2024 Apr 10;10(2):e004040. doi: 10.1136/rmdopen-2023-004040.
citation: Dubreuil M, Navarro-Compan V, Boonen A, Gaffney K, Gensler LS, de la Loge C, Vaux T, Fleurinck C, Massow U, Taieb V, Morup MF, Deodhar A, Rudwaleit M. Improved physical functioning, sleep, work productivity and overall health-related quality of life with bimekizumab in patients with axial spondyloarthritis: results from two phase 3 studies. RMD Open. 2024 Jun 4;10(2):e004202. doi: 10.1136/rmdopen-2024-004202.
citation: Cella D, de la Loge C, Fofana F, Guo S, Ellis A, Fleurinck C, Massow U, Dougados M, Navarro-Compan V, Walsh JA. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in patients with axial spondyloarthritis: psychometric properties and clinically meaningful thresholds for interpretation. J Patient Rep Outcomes. 2024 Aug 12;8(1):92. doi: 10.1186/s41687-024-00769-x.