臨床研究等提出・公開システム

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

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Subjects With Active Nonradiographic Axial Spondyloarthritis

254

The mean age of all study participants was 39.4 years (range of 18 to 76 years). Overall, there was a higher proportion of male study participants than female study participants (54.3% vs 45.7%, respectively). The majority of study participants were White (86.2%). The mean body weight and mean BMI overall were 80.91kg and 27.42kg/m2, respectively. For each treatment group, the number of study participants in the MRI+/CRP- stratification level was slightly higher (41.7%) compared with MRI+/CRP+ (31.9%) and MRI-/CRP+ (26.4%) stratification levels. Study participants were most commonly enrolled in the following countries: Poland (28.0%), the Czech Republic (20.9%), Spain (10.2%), Germany (9.4%), and the United States (7.1%). Overall, the mean times since first diagnosis and first symptoms of axSpA were 3.60 years (range: 0.1 to 31.3 years) and 9.02 years (range: 0.4 to 45.1 years), respectively. The majority of all study participants (77.6%) were positive for HLA-B27, a genetic marker associated with axSpA. Treatment groups were generally well balanced with respect to nr-axSpA-related and other Baseline disease characteristics. Prior anti-TNF therapy was used by 10.6% of all study participants. At Baseline, the majority of all study participants were using NSAID therapies (74.8%), 24.0% were on csDMARDs (8.3% on MTX, 13.0% on SSZ), 8.3% were taking oral corticosteroids, and 16.5% 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 6.80 (range: 4.1 to 9.6), the mean BASDAI spinal pain score was 7.5 (range: 4 to 10), the mean PGADA was 7.0 (range: 0 to 10), and the mean total spinal pain NRS score was 7.2 (range: 2 to 10). The mean BASFI score was 5.43 (range: 0.0 to 9.1). The geometric mean hs-CRP was 4.806mg/L (range: 0.05 to 79.06mg/L). Most study participants had an ASDAS-CRP status of vHD activity (58.3%) or HD activity (40.2%), and the mean ASDAS-CRP was 3.7133 (range: 1.959 to 5.513).

A total of 254 study participants were randomized and started the Double-Blind Treatment Period as follows: 128 study participants in the bimekizumab 160mg Q4W group and 126 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 (98.4%) and the placebo group (93.7%). The frequency of study discontinuation was low in the All study participants group (10 study participants [3.9%]) and in each of the treatment groups in the Double-Blind Treatment Period (1.6% and 6.3% in the bimekizumab 160mg Q4W and the 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 [1.6%]) and an AE (4 study participants [1.6%]). In the bimekizumab 160mg Q4W group, no study participants discontinued due to withdrawal by study participant, and 4 study participants (3.2%) discontinued due to withdrawal by study participant in the placebo group. In the Bimekizumab 160mg Q4W group, 1 study participant (0.8%) discontinued due to an AE, and 3 study participants (2.4%) in the placebo group discontinued due to an AE. A total of 242 study participants entered the Maintenance Period as follows: 126 study participants in the bimekizumab 160mg Q4W group and 116 study participants in the placebo/bimekizumab 160mg Q4W group. Of the 244 study participants who completed the Double-Blind Treatment Period, 2 study participants in the placebo/bimekizumab 160mg Q4W group discontinued the study at Week 16 and did not enter the Maintenance Period; the reason for discontinuation was due to an AE (2 study participants [1.6%]). No study participants in the bimekizumab 160mg Q4W group discontinued between the Double-Blind Treatment Period and the Maintenance Period. A total of 220 study participants (86.6%) completed the 36-week Maintenance Period, 22 study participants (8.7%) discontinued the study during the Maintenance Period, and 51 study participants (20.1%) entered and completed the SFU Period . The percentages of study participants who completed the Maintenance Period were 87.5% in the bimekizumab 160mg Q4W group and 85.7% in the placebo/bimekizumab 160mg Q4W group. The most common reasons for discontinuation during the Maintenance Period were withdrawal by study participant (12 study participants [4.7%]), due to an AE (5 study participants [2.0%]), and due to lack of efficacy (4 study participants [1.6%]) . In the bimekizumab 160mg Q4W group, 8 study participants (6.3%) discontinued due to withdrawal by study participant and 4 study participants (3.2%) in the placebo/bimekizumab 160mg Q4W group discontinued due to withdrawal by study participant. Three study participants (2.3%) in the bimekizumab 160mg Q4W group and 2 study participants (1.6%) in the placebo/bimekizumab 160mg Q4W group discontinued due to an AE. Two study participants (1.6%) in the bimekizumab 160mg Q4W group and 2 study participants (1.6%) in the placebo/bimekizumab 160mg Q4W group discontinued due to lack of efficacy. Within the participants who completed the maintence treatment period, 203 study participants (79.9%) had entered the OLE study (AS0014).

During the Double-Blind Treatment Period, TEAEs were reported at a slightly higher incidence in the bimekizumab 160mg Q4W group (80 study participants [62.5%]) compared with the placebo group (71 study participants [56.3%]) . There were no serious TEAEs in the bimekizumab 160mg Q4W group and only 1 serious TEAE reported by 1 participant (0.8%) in the placebo group. The incidence of safety topics of interest TEAEs was higher in the bimekizumab 160mg Q4W group (18 study participants [14.1%]) compared with the placebo group (8 study participants [6.3%]). Very few participants discontinued due to TEAEs: 2 study participants (1.6%) discontinued due to TEAEs in the bimekizumab 160mg Q4W group and 5 study participants (4.0%) discontinued due to TEAEs in the placebo group. Drug-related TEAEs (as determined by the Investigator) were reported at a higher incidence in the bimekizumab 160mg Q4W group (33 study participants [25.8%]) compared with the placebo group (17 study participants [13.5%]). There were no severe TEAEs in the bimekizumab 160mg Q4W group and only 1 severe TEAE reported by 1 participant (0.8%) in the placebo group. No deaths due to AEs or TEAEs were reported during the Double-Blind Treatment Period. During the Overall Period, 183 study participants (75.0%) reported a TEAE; when the TEAE incidence was adjusted for duration of exposure, the resulting EAIR was 202.27/100 participant-years. Nine study participants (3.7%) reported a serious TEAE. Seventy-five study participants (30.7%) reported a safety topics of interest TEAE. Six study participants (2.5%) reported a TEAE that led to discontinuation and 8 study participants (3.3%) permanently withdrew from IMP due to TEAEs. Drug-related TEAEs (as determined by the Investigator) were reported by 81 study participants (33.2%). Eight study participants (3.3%) reported a severe TEAE. No deaths due to AEs or TEAEs were reported during the Overall Period. Treatment-emergent AEs were the most frequently reported in the SOC of Infections and infestations in both treatment groups with higher incidence in the bimekizumab 160mg Q4W group (35.9%) compared with the placebo group (24.6%) . Treatment-emergent AEs in the next most common SOCs were Musculoskeletal and connective tissue disorders (16 study participants [12.5%] in the bimekizumab 160mg Q4W group and 7 study participants (5.6%) in the placebo group) and Gastrointestinal disorders (12 study participants [9.4%] in the bimekizumab 160mg Q4W group and 16 study participants (12.7%) in the placebo group). The most commonly reported TEAEs, by PT (>=3%), in the bimekizumab 160mg Q4W group were nasopharyngitis (10.2%), upper respiratory tract infection (7.0%), pharyngitis (3.1%), and oral candidiasis (3.1%). The most commonly reported TEAEs, by PT (>=3%), in the placebo group were upper respiratory tract infection (7.9%), nasopharyngitis (4.8%), and uveitis (3.2%). Treatment-emergent AEs were most frequently reported in the SOCs of Infections and infestations (52.0%) and Musculoskeletal and connective tissue disorders (18.0%). Treatment-emergent AEs in the next most common SOCs were Skin and subcutaneous tissue disorders (15.6%), and Gastrointestinal disorders (13.9%). Overall, the most commonly reported TEAEs, by PT (>=3%), were nasopharyngitis (12.3%), upper respiratory tract infection (9.4%), and oral candidiasis (7.4% ).

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 (47.7% vs 21.4%, respectively; p<0.001).

There was a greater least-squares (LS) mean decrease from Baseline in BASDAI total score in the bimekizumab 160mg Q4W group compared with the placebo group (-3.07 vs -1.55, respectively; p<0.001). The ASAS20 response rate was higher in the bimekizumab 160mg Q4W group compared with the placebo group (68.8% vs 38.1%, respectively; p<0.001).

254 patients with nr-axSpA were randomized. 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 nr-axSpA.

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.
-Patient has nonradiographic axial spondyloarthritis with all of the following criteria:
1.Adult-onset axial spondyloarthritis meeting Assessment of SpondyloArthritis International Society (ASAS) 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.
-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.

- 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
- 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 AxSpA, 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 (including pumping), 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

Nonradiographic Axial Spondyloarthritis

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
- Change from Baseline in BASDAI at Week 16
- ASAS20 response 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