臨床研究等提出・公開システム

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Bimekizumab in Study Participants With Moderate to Severe Hidradenitis Suppurativa

A Study to Test the Efficacy and Safety of Bimekizumab in Study Participants With Moderate to Severe Hidradenitis Suppurativa

509

The mean age of all study participants was 36.6 years of age, with a range of 18 to 75 years of age. Half of the participants were female (50.7%), and the majority of study participants were White (81.5%). The mean body weight and mean body mass index (BMI) overall were 96.09kg and 32.34kg/m2, respectively. The mean duration of disease was 7.00 years and 61.1% of study participants had Baseline Hurley Stage II (derived) and 38.9% had Baseline Hurley Stage III (derived). Based on the HS Physician's Global Assessment, 41.7% and 46.0% of participants had moderate or very severe lesions, respectively, with fewer participants classified as having severe lesions (12.4%). Overall, the mean IHS4 score was 33.2 (indicating severe disease). The mean HSSDD worst skin pain score was 5.28 and the mean HSSDD average skin pain score was 4.53. The mean DLQI Total Score was 10.8 and the mean HiSQOL Total Score was 24.35. Overall, study participants who had Baseline Hurley Stage III had higher mean total lesion counts (abscesses: 4.2, inflammatory nodules: 16.7, AN: 21.0, and draining tunnels: 5.3) than participants who had Baseline Hurley Stage II (abscesses: 2.6, inflammatory nodules: 11.1, AN: 13.7, and draining tunnels: 2.1).

A total of 509 study participants were randomized during the Initial Treatment Period as follows: 144 study participants in the BKZ 320mg Q4W group, 291 study participants in the BKZ 320mg Q2W group, and 74 study participants in the placebo group. Of the 509 randomized study participants, 506 study participants started treatment in the Initial Treatment Period. The proportion of randomized study participants who completed the Initial Treatment Period was slightly higher in the BKZ 320mg Q4W group (92.4%) and the placebo group (93.2%) compared with the BKZ 320mg Q2W group (90.0%). The frequency of study discontinuation during the Initial Treatment Period was slightly lower in the BKZ 320mg Q4W group (6.3%) and the placebo group (6.8%) compared with the BKZ 320mg Q2W group (9.6%). The most common primary reasons for discontinuation during the Initial Treatment Period were consent withdrawn by study participant (not due to AE) (4.3%) and AE (2.2%). The proportion of study participants who discontinued due to AE was slightly lower in the BKZ 320mg Q4W group (0.7%) compared with the BKZ 320mg Q2W group (3.1%). In the placebo group,1.4% of study participants discontinued due to AE. Of the 464 study participants who completed the Initial Treatment Period, 1 study participant in the BKZ 320mg Q2W group discontinued the study at Week 16 and did not enter the Maintenance Treatment Period due to consent withdrawn (not due to AE). A total of 463 study participants entered the Maintenance Treatment Period as follows: 133 study participants in the BKZ 320mg Q4W/Q4W group, 130 study participants in the BKZ 320mg Q2W/Q4W group, 131 study participants in the BKZ 320mg Q2W/Q2W group, and 69 study participants in the placebo/BKZ 320mg Q2W group. During the Maintenance Treatment Period, 16.4% of study participants discontinued the study. The frequency of study discontinuation during the Maintenance Treatment Period was lower in the placebo/BKZ 320mg Q2W group (11.6%) compared with the BKZ 320mg Q4W/Q4W, BKZ 320mg Q2W/Q4W, and BKZ 320mg Q2W/Q2W groups (18.0%, 17.7%, and 16.0%, respectively). The most common primary reasons for discontinuation during the Maintenance Treatment Period were consent withdrawn by study participant (not due to AE) (7.8%) and AE (3.7%). The percentage of study participants who discontinued due to consent withdrawn was similar across treatment groups (range: 6.8% to 8.7%).

During the Initial Treatment Period, TEAEs were reported at a slightly higher incidence in the BKZ total group (60.2%) compared with the placebo group (56.8%). Treatment emergent AEs were reported at a lower incidence in the BKZ 320mg Q4W group (51.4%) compared with the BKZ 320mg Q2W group (64.5%). The incidence of serious TEAEs was low in the BKZ total group (2.8%), and no serious TEAEs were reported in the placebo group. The incidence of serious TEAEs was similar in the BKZ 320mg Q4W group (2.1%) compared with the BKZ 320mg Q2W group (3.1%). A total of 3.5% of study participants in the BKZ total group and no study participants in the placebo group discontinued due to TEAEs. The proportion of study participants in the BKZ 320mg Q4Wgroup (2.1%) and the BKZ 320mg Q2W group (4.1%) who discontinued due to TEAEs was considered similar. Drug related TEAEs (as determined by the Investigator) were reported at a higher incidence in the BKZ total group (33.1%) compared with the placebo group (10.8%). Drug related TEAEs were reported at a lower incidence in the BKZ 320mg Q4W group (26.8%) compared with the BKZ 320mg Q2W group (36.2%). The incidence of severe TEAEs was similar in the BKZ total group (3.9%) compared with the placebo group (2.7%). The incidence of severe TEAEs was similar in the BKZ 320mg Q4W group (3.5%) compared with the BKZ 320mg Q2W group (4.1%). No deaths were reported during the Initial Treatment Period. During the Initial Treatment Period, the most commonly reported TEAEs, by PT, in the BKZ total group were hidradenitis (8.8%), oral candidiasis (6.7%), and headache (5.8%), and in the placebo group were headache (9.5%), diarrhoea (8.1%), and hidradenitis (6.8%). Of the most common TEAEs in the BKZ total group and the placebo group, the incidence was higher in the BKZ total group compared with the placebo group for oral candidiasis (6.7% vs 0%), similar for hidradenitis (8.8% vs 6.8%), and slightly lower for headache (5.8% vs 9.5%) and diarrhoea (5.3% vs 8.1%). The most commonly reported TEAEs, by PT, in the BKZ 320mg Q4W group were hidradenitis (9.2%), vulvovaginal candidiasis (5.6%) and headache (4.9%), and in the BKZ 320mg Q2W group were hidradenitis (8.6%), oral candidiasis (8.3%), headache (6.2%), and diarrhoea (6.2%). Of the most common TEAEs in the BKZ 320mg Q4W group and the BKZ 320mg Q2W group, the incidence was higher in the BKZ 320mg Q4W group compared with the BKZ 320mg Q2W group for vulvovaginal candidiasis (5.6% vs 0.3%), similar for hidradenitis (9.2% vs 8.6%) and headache (4.9% vs 6.2%), and slightly lower for diarrhoea (3.5% vs 6.2%) and oral candidiasis (3.5% vs 8.3%). During the Overall Period, TEAEs were reported at a lower incidence in the BKZ 320mg Q4W/Q4W group (79.6%) compared with the BKZ 320mg Q2W/Q2W group (84.7%). The incidence of serious TEAEs was similar in the BKZ 320mg Q4W/Q4W group (4.9%) compared with the BKZ 320mg Q2W/Q2W group (6.9%). The proportion of study participants who discontinued due to TEAEs was similar in the BKZ 320mg Q4W/Q4W group (5.6%) compared with the BKZ 320mg Q2W/Q2W group (6.3%). The incidence of drug related TEAEs (as determined by the Investigator) was lower in the BKZ 320mg Q4W/Q4W group (35.2%) compared with the BKZ 320mg Q2W/Q2W group (50.0%). The incidence of severe TEAEs was similar in the BKZ 320mg Q4W/Q4W group (9.9%) compared with the BKZ 320mg Q2W/Q2W group (9.0%). No deaths were reported during the Overall Period. During the Overall Period in the AMS, the most commonly reported TEAEs, by PT, in the BKZ total group were hidradenitis (18.0%), oral candidiasis (12.8%), and headache (8.6%). The most commonly reported TEAEs, by PT, in the BKZ 320mg Q4W/Q4W group were hidradenitis (18.3%), oral candidiasis (9.9%), and headache (9.2%). The most commonly reported TEAEs, by PT, in the BKZ 320mg Q2W/Q2W group were hidradenitis (18.1%), oral candidiasis (15.3%), and nasopharyngitis (11.1%). During the Overall Period in the AMS, there were generally similar incidences of the most common TEAEs (>=5%) reported by study participants in the BKZ 320mg Q4W/Q4W group compared with the BKZ 320mg Q2W/Q2W group, with a few exceptions. The incidence of vulvovaginal candidiasis was slightly higher in the BKZ 320mg Q4W/Q4W group (7.0%) compared with the BKZ 320mg Q2W/Q2W group (2.1%). The incidences were slightly lower in the BKZ 320mg Q4W/Q4W group compared with the BKZ 320mg Q2W/Q2W group for folliculitis (5.6% vs 9.0%), corona virus infection (4.2% vs 7.6%), and pyrexia (2.1% vs 6.9%). The incidences were lower in the BKZ 320mg Q4W/Q4W group compared with the BKZ 320mg Q2W/Q2W group for oral candidiasis (9.9% vs 15.3%) and nasopharyngitis (5.6% vs 11.1%).

Both the BKZ 320mg Q4W and BKZ 320mg Q2W groups demonstrated a superior HiSCR50 responder rate at Week 16 compared with the placebo group (53.8% and 52.0% vs 32.2%, respectively). These differences were considered clinically meaningful, with statistically significant odds ratios vs placebo of 2.422 for BKZ 320mg Q4W (p=0.004) and 2.287 for BKZ 320mg Q2W (p=0.003). The HiSCR50 responder rates at Week 16 were similar for the BKZ 320mg Q4W and BKZ 320mg Q2W groups (53.8% and 52.0%, respectively).

Both the BKZ 320mg Q4W and BKZ 320mg Q2W groups had higher HiSCR75 responder rates at Week 16 compared with the placebo group, and these differences were clinically meaningful and statistically significant (33.7% and 35.7% vs 15.6%; p=0.007 and p=0.002, respectively). The HiSCR75 responder rates at Week 16 were similar for the BKZ 320mg Q4W and BKZ 320mg Q2W groups (33.7% and 35.7%, respectively). The flare rate at any time during the Initial Treatment Period was similar in the BKZ 320mg Q4W and BKZ 320mg Q2W groups compared with the placebo group (23.6% and 28.8% vs 28.0%; p=0.497 and p=0.868, respectively). Both the BKZ 320mg Q4W (LS mean [SE]: -4.776 [0.529]; 95% CI: -5.813, -3.738) and BKZ 320mg Q2W (LS mean [SE]: -4.692 [0.405]; 95% CI: -5.486, -3.897) groups had greater improvements from Baseline in DLQI Total Score (indicated by decreases from Baseline) at Week 16 compared with the placebo group (LS mean [SE]: -2.382 [0.640]; 95% CI: 3.636, 1.128). A clinically meaningful improvement from Baseline in the mean DLQI Total Score at Week 16 was observed for both the BKZ 320mg Q4W and BKZ 320mg Q2W groups (mean change of -4.14 and 4.49, respectively). The mean change in DLQI Total Score in the placebo group did not reach the threshold for clinically meaningful improvement (mean change of -3.07). The mean changes from Baseline in DLQI Total Score at Week 16 were similar for the BKZ 320mg Q4W and BKZ 320mg Q2W groups (-4.14 and -4.49, respectively). Both the BKZ 320mg Q4W and BKZ 320mg Q2W groups had greater improvements from Baseline in HSSDD worst skin pain score at Week 16 compared with the placebo group (LS mean [SE]: -1.197 [0.272]and -1.564 [0.228] vs -0.299 [0.334], respectively). The mean changes from Baseline in HSSDD worst skin pain score at Week 16 were similar for the BKZ 320mg Q4W and BKZ 320mg Q2W groups. Both the BKZ 320mg Q4W and BKZ 320mg Q2W groups had higher responder rates (28.6% and 31.8%, respectively) based on the HSSDD worst skin pain response threshold for clinically meaningful within-patient change compared with the placebo group (10.9%) at Week 16 (odds ratio [97.5% CI]: 3.273 [0.974, 10.997] and 3.756 [1.189, 11.867], respectively). Differences in responder rates between the BKZ 320mg Q4W and BKZ 320mg Q2W groups compared with the placebo group were clinically meaningful. The cumulative distribution function curves for change from Baseline in HSSDD worst skin pain score at Week 16 for the BKZ 320mg Q4W and BKZ 320mg Q2W groups were clearly separated from the placebo curve at Week 16, providing further evidence of the higher response observed in both the BKZ 320mg Q4W and the BKZ 320mg Q2W groups compared with placebo, regardless of the threshold considered to define response. The responder rates based on HSSDD worst skin pain score at Week 16 were similar for the BKZ 320mg Q4W and BKZ 320mg Q2W groups (28.6% and 31.8%, respectively).

In this study, BKZ significantly reduced signs of disease in patients with moderate-to-severe HS compared with placebo. The safety profile of BKZ in this study was consistent with other indications and with the selective IL-17A inhibitor, which is approved for use in HS in abroad. This study demonstrated that BKZ was well tolerated by patients with moderate to severe HS and that it produced rapid, deep, and maintained clinically meaningful improvements in physician-assessed and PRO measures to week 48.

Dec. 20, 2024

Yes

Data from this trial 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 individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, 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.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.

UCB Japan Co., Ltd.

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

CTR_SCC_UCBJapan@UCB.com

UCB Japan Co., Ltd.

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

+81-368647587

CTR_SCC_UCBJapan@UCB.com

completed

July. 09, 2020

Interventional

Randomized, double-blind, placebo-controlled, multicenter

treatment purpose

3

- Participant must be at least 18 years of age, at the time of signing the informed consent. If a study participant is <20 years of age, written informed consent will be obtained from both the study participant and the legal representative.
- Study participants must have a diagnosis of Hidradenitis Suppurativa (HS) based on clinical history and physical examination for at least 6 months prior to the Baseline visit
- Study participant must have HS lesions present in at least 2 distinct anatomic areas (eg, left and right axilla), 1 of which must be at least Hurley Stage II or Hurley Stage III at both the Screening and Baseline visits
- Study participant must have moderate to severe HS defined as a total of >_5 inflammatory lesions (ie, number of abscesses plus number of inflammatory nodules) at both the Screening and Baseline visits
- Study participant must have had an inadequate response to a course of a systemic antibiotic for treatment of HS as assessed by the Investigator through study participant interview and review of medical history
- A female study participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP) OR
b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 20 weeks after the last dose of investigational medicinal product (IMP)

- Draining tunnel count of >20 at the Baseline Visit
- Any other active skin disease or condition (eg, bacterial cellulitis, candida intertrigo, extensive condyloma) that may, in the opinion of the Investigator, interfere with the assessment of hidradenitis suppurativa (HS)
- Study participant has a diagnosis of sarcoidosis, systemic lupus erythematosus, or active inflammatory bowel disease (IBD)
- Primary immunosuppressive condition, including taking immunosuppressive therapy following an organ transplant, or has had a splenectomy
- Female who is breastfeeding, pregnant, or plans to become pregnant during the study or within 20 weeks following the final dose of investigational medicinal product (IMP)
- Active infection or history of certain infection(s)
- Active tuberculosis (TB) infection, latent TB infection, high risk of exposure to TB infection, current or history of nontuberculous mycobacterium (NTM) infection
- Concurrent malignancy. Study participants with a history of malignancy within the past 5 years prior to the Screening Visit are excluded, EXCEPT if the malignancy was a cutaneous squamous or basal cell carcinoma, or in situ cervical cancer that has been treated and is considered cured
- History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease
- Known hypersensitivity to any components of bimekizumab or comparative drugs as stated in this protocol
- Concomitant and prior medication restrictions
- Myocardial infarction or stroke within the 6 months prior to the Screening Visit
- Presence of active suicidal ideation, or moderately severe major depression or severe major depression
- Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening

Both

Hidradenitis Suppurativa

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 : 320mg 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
Percentage of participants achieving clinical response as measured by Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at Week 16

safety
efficacy
1. Percentage of participants achieving clinical response as measured by Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 16
2. Percentage of participants with Flare by Week 16
3. Absolute change from Baseline in Skin Pain score at Week 16
4. Absolute change from Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16
5. Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
6. Percentage of participants with serious adverse events (SAEs) during the study
7. Percentage of participants with treatment-emergent adverse events (TEAEs) leading to withdrawal from the study

+81-11-221-8807

May. 26, 2020