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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Bimekizumab in Subjects With Active Ankylosing Spondylitis

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

254

The mean age of all study participants was 40.4 years with a range of 19 to 80 years. The majority of study participants were male (72.3%) and White (80.4%). The mean body weight and mean BMI overall were 80.43kg and 26.86kg/m2, respectively. For each treatment group, the proportions of study participants enrolled in each region and study participants with or without prior TNFa inhibitor exposure were similar (region and prior TNFa inhibitor exposure were stratification factors for randomization). Study participants were most commonly enrolled in the following countries: Poland (26.2%), the Czech Republic (16.9%), China (13.3%), Germany (11.1%), and Spain (10.2%). Overall, the mean times since first diagnosis and first symptoms of AS were 6.39 years (range: 0.1 to 41.0 years) and 13.46 years (range: 0.4 to 59.1 years), respectively. The majority of all study participants (85.5%) were positive for HLA-B27, a genetic marker associated with AS. Treatment groups were generally well balanced with respect to AS-related and other Baseline disease characteristics. Prior anti-TNF therapy was used by 16.3% of all study participants. At Baseline, the majority of all study participants were using NSAID therapies (79.8%), 20.2% were on csDMARDs (3.6% on MTX, 16.0% on SSZ), 6.9% were taking oral corticosteroids, and 13.6% were on analgesic/opioid therapies. Baseline efficacy characteristics were well balanced across treatment groups, consistent with the study's inclusion criteria, and reflective of the active disease at enrollment in the study: BASDAI>=4 and BASDAI spinal pain>=4 (question 2). Overall, the mean BASDAI total score was 6.47 (range: 3.7 to 9.4), the mean BASDAI spinal pain score was 7.4 (range: 4 to 10), the mean PGADA was 6.7 (range: 0 to 10), and the mean Total Spinal Pain NRS score was 7.2 (range: 2 to 10). The mean BASFI score was 5.24 (range: 0.0 to 9.6). The geometric mean hs-CRP was 6.600mg/L (range:0.05 to 105.41mg/L). Most study participants had an ASDAS-CRP status of vHD activity (59.3%) or HD activity (39.5%), and the mean ASDAS-CRP was 3.7156 (range: 1.792 to 6.018).

A total of 332 study participants were randomized and started the Double-Blind Treatment Period as follows: 221 study participants in the bimekizumab 160mg Q4W group and 111 study participants in the placebo group. The percentages of study participants who completed the Double-Blind Treatment Period were similar in the bimekizumab 160mg Q4W group (96.4%) and the placebo group (98.2%). The frequency of study discontinuation during the Double-Blind Treatment Period was low between the treatment groups (3.6% and 1.8% in the bimekizumab 160mg Q4W and placebo groups, respectively). The most common primary reasons for discontinuation during the Double-Blind Treatment Period were due to withdrawal by study participant (4 study participants [1.2%]) and an AE (3 study participants [0.9%]). In the bimekizumab 160mg Q4W group, 3 study participants (1.4%) discontinued due to withdrawal by study participant, and in the placebo group 1 study participant (0.9%) discontinued due to withdrawal by study participant. In the bimekizumab 160mg Q4W group, 3 study participants (1.4%) discontinued due to an AE, and no study participants in the placebo group discontinued due to AE. Of the 322 study participants who completed the Double-Blind Treatment Period, 3 study participants in the bimekizumab 160mg Q4W group discontinued the study at Week 16 and did not enter the Maintenance Period. The primary reasons for discontinuation in the bimekizumab 160mg Q4W group between the Double-Blind Treatment Period and Maintenance Period were due to withdrawal by study participant (2 study participants [0.9%]) and due to an AE (1 study participant [0.5%]). No study participant in the placebo/bimekizumab 160mg Q4W group discontinued between the Double-Blind Treatment Period and the Maintenance Period. A total of 298 study participants completed the Maintenance Period, and 21 study participants discontinued the study during the Maintenance Period. The percentages of study participants who completed the Maintenance Period were similar between the bimekizumab 160mg Q4W group (88.7%) and the placebo/bimekizumab 160mg Q4W group (91.9%). A total of 50 study participants (15.1%) entered and completed the SFU Period. The most common reason for discontinuation during the Maintenance Period was due to an AE (11 study participants [3.3%]). In the bimekizumab 160mg Q4W group, 7 study participants (3.2%) discontinued due to an AE, and 4 study participants (3.6%) in the placebo/bimekizumab 160mg Q4W group discontinued due to an AE.

During the Double-Blind Treatment Period, TEAEs were reported at a higher incidence in the bimekizumab 160mg Q4W group (120 study participants [54.3%]) compared with the placebo group (48 study participants [43.2%]). The incidence of serious TEAEs was low in both treatment groups; 5 study participants (2.3%) in the bimekizumab 160mg Q4W group and 1 study participant (0.9%) in the placebo group. The incidence of safety topics of interest TEAEs was higher in the bimekizumab 160mg Q4W group (39 study participants [17.6%]) compared with the placebo group (7 study participants [6.3%]). In the bimekizumab 160mg Q4W group, 6 study participants (2.7%) discontinued due to TEAEs, and no study participants in the placebo group discontinued due to TEAEs. Drug-related TEAEs (as determined by the Investigator) were reported at a higher incidence in the bimekizumab 160mg Q4W group (66 study participants [29.9%]) compared with the placebo group (19 study participants [17.1%]). In the bimekizumab 160mg Q4W group, 4 study participants (1.8%) had a severe TEAE, and no study participants in the placebo group had a severe TEAE. No deaths due to AEs or TEAEs were reported during the Double-Blind Treatment Period. During the Overall Period, 250 study participants (75.8%) reported a TEAE, and 20 study participants (6.1%) reported a serious TEAE. One hundred and eight study participants (32.7%) reported a safety topic of interest TEAE. Fifteen study participants (4.5%) experienced a TEAE that led to discontinuation, and 16 study participants (4.8%) permanently withdrew from IMP due to TEAEs. Drug-related TEAEs (as determined by the Investigator) were reported by 135 study participants (40.9%). Fourteen study participants (4.2%) reported a severe TEAE. No deaths due to AEs or TEAEs were reported during the Overall Period. Treatment-emergent AEs were most frequently reported in the SOC of Infections and infestations, and the incidence was higher in the bimekizumab 160mg Q4W group (28.1%) compared with the placebo group (22.5%). Treatment-emergent AEs in the next most common SOC, Gastrointestinal disorders, were reported by 29 study participants (13.1%) in the bimekizumab 160mg Q4W group and 11 study participants (9.9%) in the placebo group. The most commonly reported TEAEs, by PT (>=3%), in the bimekizumab 160mg Q4W group were nasopharyngitis (7.7%), oral candidiasis (4.5%), headache (4.1% ), and diarrhea (3.2%). The most commonly reported TEAEs, by PT (>=3%), in the placebo group were upper respiratory tract infection (7.2%), headache (4.5%), uveitis (3.6%), nasopharyngitis (3.6% ), rhinitis (3.6%), and cough (3.6%). Treatment-emergent AEs were most frequently reported in the SOCs of Infections and infestations (46.1%) and Gastrointestinal disorders (23.0%). Overall, the most commonly reported TEAEs, by PT (>=3%), were nasopharyngitis (9.1%), upper respiratory tract infection (6.4%), oral candidiasis (6.1%), headache (5.5%), diarrhea (5.5%), arthralgia (3.6%), hypertension (3.6%), pharyngitis (3.3%), rash (3.3%), and nausea (3.0%).

The bimekizumab 160mg Q4W group had a higher ASAS40 response rate compared with the placebo group at Week 16 that was statistically significant and clinically meaningful (44.8% vs 22.5%, respectively; p<0.001) .

The bimekizumab 160mg Q4W group had a higher ASAS20 response rate compared with the placebo group at Week 16 that was statistically significant (66.1% vs 43.2%, respectively; p<0.001). The bimekizumab 160mg Q4W group had an LS mean decrease from Baseline in BASDAI total score at Week 16 (decreases reflect improvement) that was greater than the placebo group and the difference was statistically significant (-2.74 vs -1.70, respectively; p<0.001).

332 with AS were randomised. At week 16, primary and all ranked secondary endpoints were met in this trial. Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with AS.

June. 07, 2024

Jan. 17, 2023

https://ard.bmj.com/content/82/4/515.abstract

Yes

Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.clinicalstudydatarequest.com and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if a determination is made that the data cannot be adequately anonymized.

UCB Japan Co., Ltd.

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

CTR-JRCT.UCBJapan@ucb.com

UCB Japan Co., Ltd.

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

+81-3-6864-7587

CTR_SCC_UCBJapan@UCB.com

completed

Sept. 30, 2019

Interventional

MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

treatment purpose

3

- Male or female patients at least 18 years of age
- Subject has ankylosing spondylitis as per the Modified New York (mNY) criteria with documented radiologic evidence, and at least 3 months of symptoms with age at symptom onset less than 45 years
- Subjects has moderate-to-severe active disease defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >=4 AND spinal pain >=4 on a 0 to 10 Numeric Rating Scale
- Patients must have inadequate response to NSAIDs, intolerance to administration of at least 1 NSAID, or contraindication(s) to NSAID therapy
- Patients who have taken a tumor necrosis factor alpha (TNF-alpha) 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

- Total ankylosis of the spine
- Treatment with more than 1 TNF-alpha inhibitor and/or more than 2 additional non-TNF-alpha biological response modifiers, or any interleukin (IL)-17 biological response modifier at any time are excluded
- Active infection or history of recent serious infections
- Viral hepatitis B or C or human immunodeficiency virus (HIV) infection or human T-cell lymphotropic virus type-1 (HTLV-1).
- 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 AS, including but not limited
to rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, reactive arthritis, Crohn's disease, ulcerative colitis, or synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome
- 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

Both

Ankylosing Spondylitis

investigational material(s)
Generic name etc : UCB4940
INN of investigational material : bimekizumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : 160mg administered by sc injection

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

efficacy
Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 16

safety
efficacy
- ASAS40 response at Week 16 in TNF-alpha inhibitor-naive subjects
- ASAS20 response at Week 16
- Change from Baseline in BASDAI at Week 16
- ASAS partial remission (ASAS-PR) at Week 16
- Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) at Week 16
- ASAS5/6 response at Week 16
- Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16
- Change from Baseline in nocturnal spinal pain (NRS) at Week 16
- Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16
- Change from Baseline in the Short Form 36-Item Health Survey (SF-36) physical component summary (PCS) at Week 16
- Change from Baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at Week 16
- Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the subgroup of subjects with enthesitis at Baseline at Week 16
- Enthesitis-free state based on the MASES Index in the subgroup of subjects with enthesitis at Baseline at Week 16
- Incidence of treatment-emergent adverse events (TEAEs)
- Incidence of serious adverse events (SAEs)
- Adverse events (AEs) leading to withdrawal from IMP

+81-11-706-7061

June. 11, 2019