BE MOBILE 1: A Study to Evaluate the Efficacy and Safety of Bimekizumab in Subjects With Active Nonradiographic Axial Spondyloarthritis
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bimekizumab Subjects randomized to this arm will receive bimekizumab during the Double-Blind Treatment Period and the Maintenance Period. |
Drug: Bimekizumab
Subjects will receive bimekizumab at pre-specified time-points.
Other Names:
|
| Placebo Comparator: Placebo Subjects randomized to this arm will receive placebo during the Double-Blind Treatment Period and receive bimekizumab during the Maintenance Period. |
Drug: Bimekizumab
Subjects will receive bimekizumab at pre-specified time-points.
Other Names:
Other: Placebo
Subjects will receive placebo at pre-specified time-points during the Double-Blind Treatment Period.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 16 [Week 16]
ASAS40 will be calculated relative to Baseline. The Assessment of SpondyloArthritis International Society (ASAS) criteria for 40% improvement are 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) in at least 3 of the 4 domains and no worsening at all in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity (PGADA) Pain assessment (the total spinal pain, NRS score) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI))
Secondary Outcome Measures
- Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response in TNFα inhibitor-naïve subjects at Week 16 [Week 16]
ASAS40 will be calculated relative to Baseline. The Assessment of SpondyloArthritis International Society (ASAS) criteria for 40% improvement are 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) in at least 3 of the 4 domains and no worsening at all in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity (PGADA) Pain assessment (the total spinal pain, NRS score) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI))
- Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) total score at Week 16 [Baseline, Week 16]
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
- Assessment of SpondyloArthritis International Society 20% response criteria (ASAS20) response at Week 16 [Week 16]
ASAS20 will be calculated relative to Baseline. The Assessment of SpondyloArthritis International Society (ASAS) criteria for 20% improvement are defined as relative improvements of at least 20%, and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains and absence of deterioration in the potential remaining domain. The domains are: Patient's Global Assessment of Disease Activity (PGADA) Pain assessment (the total spinal pain, NRS score) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI))
- Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR) at Week 16 [Week 16]
The Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR) is defined as a score of <=2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
- Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) at Week 16 [Week 16]
Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) is achieved when there is a reduction (improvement) >= 2.0 in the Ankylosing Spondylitis Disease Activity Score (ASDAS) relative to Baseline. ASDAS is calculated as the sum of the following components: 0.121 × Total back pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm of the C-reactive protein (CRP) [mg/L] + 1) Total back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). High ASDAS scores mean worse disease. If a subjects achieves the ASDAS-MI it indicates a major improvement of their disease.
- Assessment of SpondyloArthritis International Society (ASAS) 5/6 response at Week 16 [Week 16]
The Assessment of SpondyloArthritis International Society (ASAS) 5/6 response is defined as achieving at least 20% improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
- Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16 [Baseline, Week 16]
The Bath Ankylosing Spondylitis Functional Index (BASFI) assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 ('Easy') to 10 ('Impossible'). The BASFI is the mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating better physical function. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
- Change from Baseline in nocturnal spinal pain score Numeric Rating Scale (NRS) at Week 16 [Baseline, Week 16]
Nocturnal spinal pain experienced by ankylosing spondylitis (AS) subjects is measured by one question: pain in the spine at night due to AS?. When responding, the subject is to consider the average amount of pain in the preceding week. It is assessed on a numerical scale (0 to 10 units). A lower score indicates less pain and an improvement of the outcome.
- Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) total score at Week 16 [Baseline, Week 16]
The Ankylosing Spondylitis Quality of Life (ASQoL), a validated disease-specific 18-item questionnaire, has been developed specifically for measuring health-related quality of life (HRQoL) in subjects with ankylosing spondylitis (AS) and has shown to be responsive in axial spondyloarthritis (axSpA). The ASQoL score ranges from 0 to 18 with a higher score indicating worse HRQoL.
- Change from Baseline in the Short Form 36-Item Health Survey (SF-36) physical component summary (PCS) score at Week 16 [Baseline, Week 16]
There are 8 SF-36 domain scores. In addition to domain scores, the PCS scores are calculated from the 8 domains. Each of the 8 domain scores and the component summary scores ranging from 0 to 100, with higher scores indicating better health status. A larger positive value in change from Baseline indicates an improvement.
- Change from Baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at Week 16 [Baseline, Week 16]
The Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) characterizes the spinal mobility of subjects with axial Spondyloarthritis (SpA) and Ankylosing Spondylitis (AS). It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
- Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the subgroup of subjects with enthesitis at Baseline at Week 16 [Baseline, Week 16]
The Maastricht Ankylosing Spondylitis Enthesitis (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 scored as 0 or 1 and then summed for a possible score of 0 to 13. A higher score indicates worsening.
- Enthesitis-free state based on the Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) Index in the subgroup of subjects with enthesitis at Baseline at Week 16 [Baseline, Week 16]
The Maastricht Ankylosing Spondylitis Enthesitis (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 scored as 0 or 1 and then summed for a possible score of 0 to 13. A higher score indicates worsening.
- Incidence of treatment-emergent adverse events (TEAEs) during the study [From Baseline (Day 1) until Safety-Follow-Up (up to Week 72)]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 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.
- Incidence of treatment-emergent serious adverse events (SAEs) during the study [From Baseline (Day 1) until Safety-Follow-Up (up to Week 72)]
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 with 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
- Treatment-emergent adverse events (AEs) leading to withdrawal from investigational medicinal product (IMP) during the study [From Baseline (Day 1) until Safety-Follow-Up (up to Week 72)]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female patients at least 18 years of age
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Patient has nonradiographic axial spondyloarthritis (nr-axSpA) with all of the following criteria:
-
Adult-onset axial spondyloarthritis meeting Assessment of SpondyloArthritis International Society (ASAS) classification criteria
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Inflammatory back pain for at least 3 months
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Age at symptom onset of less than 45 years
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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
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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
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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:
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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
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Active infection or history of recent serious infections
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Viral hepatitis B or C or human immunodeficiency virus (HIV) infection
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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
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Known tuberculosis (TB) infection, at high risk of acquiring TB infection, or current or history of nontuberculous mycobacterium (NTMB) infection
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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
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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
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Presence of active suicidal ideation, or moderately severe major depression or severe major depression
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Female patients who are breastfeeding, pregnant, or planning to become pregnant during the study
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Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | As0010 50131 | Mesa | Arizona | United States | 85210 |
| 2 | As0010 50052 | Phoenix | Arizona | United States | 85032 |
| 3 | As0010 50062 | Sun City | Arizona | United States | 85351 |
| 4 | As0010 50060 | Upland | California | United States | 91786 |
| 5 | As0010 50059 | Ormond Beach | Florida | United States | 32174 |
| 6 | As0010 50056 | Sarasota | Florida | United States | 34239 |
| 7 | As0010 50015 | Hagerstown | Maryland | United States | 21740 |
| 8 | As0010 50016 | Saint Louis | Missouri | United States | 63141 |
| 9 | As0010 50055 | Portland | Oregon | United States | 97239-3011 |
| 10 | As0010 50020 | Duncansville | Pennsylvania | United States | 16635 |
| 11 | As0010 50012 | Memphis | Tennessee | United States | 38119 |
| 12 | As0010 50057 | Dallas | Texas | United States | 75231 |
| 13 | As0010 50036 | Mesquite | Texas | United States | 75150 |
| 14 | As0010 50061 | Spokane | Washington | United States | 99204 |
| 15 | As0010 40004 | Bruxelles | Belgium | ||
| 16 | As0010 40003 | Genk | Belgium | ||
| 17 | As0010 40001 | Gent | Belgium | ||
| 18 | As0010 40002 | Merksem | Belgium | ||
| 19 | As0010 40006 | Plovdiv | Bulgaria | ||
| 20 | As0010 40007 | Plovdiv | Bulgaria | ||
| 21 | As0010 40005 | Sofia | Bulgaria | ||
| 22 | As0010 40008 | Sofia | Bulgaria | ||
| 23 | As0010 20040 | Beijing | China | ||
| 24 | As0010 20021 | Chengdu | China | ||
| 25 | As0010 20019 | Guangzhou | China | ||
| 26 | As0010 20034 | Hefei | China | ||
| 27 | As0010 20024 | Nanjing | China | ||
| 28 | As0010 20018 | Shanghai | China | ||
| 29 | As0010 20020 | Shanghai | China | ||
| 30 | As0010 20026 | Shanghai | China | ||
| 31 | As0010 20025 | Wenzhou | China | ||
| 32 | As0010 40011 | Brno | Czechia | ||
| 33 | As0010 40009 | Pardubice | Czechia | ||
| 34 | As0010 40013 | Praha 11 | Czechia | ||
| 35 | As0010 40016 | Praha 2 | Czechia | ||
| 36 | As0010 40014 | Praha 4 | Czechia | ||
| 37 | As0010 40015 | Praha | Czechia | ||
| 38 | As0010 40010 | Uherske Hradiste | Czechia | ||
| 39 | As0010 40012 | Zlin | Czechia | ||
| 40 | As0010 40018 | Boulogne Billancourt | France | ||
| 41 | As0010 40022 | Limoges | France | ||
| 42 | As0010 40025 | Berlin | Germany | ||
| 43 | As0010 40029 | Hamburg | Germany | ||
| 44 | As0010 40024 | Hanover | Germany | ||
| 45 | As0010 40027 | Herne | Germany | ||
| 46 | As0010 40078 | Leipzig | Germany | ||
| 47 | As0010 40026 | Ratingen | Germany | ||
| 48 | As0010 40032 | Debrecen | Hungary | ||
| 49 | As0010 40031 | Szeged | Hungary | ||
| 50 | As0010 40080 | Szombathely | Hungary | ||
| 51 | As0010 40033 | Székesfehérvár | Hungary | ||
| 52 | As0010 20030 | Chuo-ku | Japan | ||
| 53 | As0010 20039 | Iruma-gun | Japan | ||
| 54 | As0010 20036 | Kawachinagano | Japan | ||
| 55 | As0010 20045 | Kita-gun | Japan | ||
| 56 | As0010 20065 | Kitakyushu | Japan | ||
| 57 | As0010 20038 | Nankoku-shi | Japan | ||
| 58 | As0010 20037 | Osaka | Japan | ||
| 59 | As0010 20084 | Saga | Japan | ||
| 60 | As0010 20048 | Saitama | Japan | ||
| 61 | As0010 20031 | Sapporo | Japan | ||
| 62 | As0010 20035 | Tokyo | Japan | ||
| 63 | As0010 40038 | Elblag | Poland | ||
| 64 | As0010 40042 | Krakow | Poland | ||
| 65 | As0010 40037 | Lublin | Poland | ||
| 66 | As0010 40044 | Poznan | Poland | ||
| 67 | As0010 40040 | Torun | Poland | ||
| 68 | As0010 40041 | Warszawa | Poland | ||
| 69 | As0010 40039 | Wroclaw | Poland | ||
| 70 | As0010 40043 | Wroclaw | Poland | ||
| 71 | As0010 40045 | A Coruna | Spain | ||
| 72 | As0010 40046 | Cordoba | Spain | ||
| 73 | As0010 40047 | Madrid | Spain | ||
| 74 | As0010 40048 | Santiago de Compostela | Spain | ||
| 75 | As0010 40049 | Sevilla | Spain | ||
| 76 | As0010 40052 | Ankara | Turkey | ||
| 77 | As0010 40053 | Ankara | Turkey | ||
| 78 | As0010 40050 | Istanbul | Turkey | ||
| 79 | As0010 40051 | Izmir | Turkey | ||
| 80 | As0010 40057 | Edinburgh | United Kingdom | ||
| 81 | As0010 40056 | Leeds | United Kingdom | ||
| 82 | As0010 40054 | London | United Kingdom | ||
| 83 | As0010 40055 | Norwich | United Kingdom |
Sponsors and Collaborators
- UCB Biopharma SRL
Investigators
- Study Director: UCB Cares, 001 844 599 2273
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AS0010
- 2017-003064-13