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A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Izokibep in Subjects with Moderate to Severe Hidradenitis Suppurativa

Hidradenitis Suppurativa Phase 3 Study of Izokibep

258

Placebo-Izokibep 160 mg QW group: placebo QW from Day 1/Week 0 to Week 15, then Izokibep 160 mg QW from Week 16 to Week 51 Overall Number of Subjects: 129 Age (years), mean (SD): 37.4 (12.85) Age, group, n(%): <65 years: 125 (96.9%)/>=65 years: 4 (3.1%) Sex, n(%): Male: 40 (31.0%)/Female: 89 (69.0%) Race, n(%): White: 90 (69.8%)/Black or African American: 28 (21.7%)/Asian: 10 (7.8%)/American Indian or Alaska Native: 0 (0%)/Native Hawaiian or Other Pacific Islander: 0 (0%)/Other: 1 (0.8%) Ethnicity, n(%): Not Hispanic or Latino:108 (83.7%)/Hispanic or Latino: 18 (14.0%)/Not Reported: 1 (0.8%)/ Unknown: 2 (1.6%) Izokibep 160 mg QW group: Izokibep 160 mg QW from Day 1/Week 0 to Week 51 Overall Number of Subjects: 129 Age (years), mean (SD): 37.1 (11.89) Age, group, n(%): <65 years: 127 (98.4%)/>=65 years: 2 (1.6%) Sex, n(%): Male: 40 (31.0%) /Female: 89 (69.0%) Race, n(%): White: 91 (70.5%)/Black or African American: 21 (16.3%)/Asian: 8 (6.2%)/American Indian or Alaska Native: 3 (2.3%)/Native Hawaiian or Other Pacific Islander: 1 (0.8%)/Other: 5 (3.9%) Ethnicity, n(%): Not Hispanic or Latino: 115 (89.1%)/Hispanic or Latino: 12 (9.3%)/Not Reported: 1 (0.8%)/ Unknown: 1 (0.8%)

A total of 258 subjects were enrolled in Canada, France, Germany, Hungary, Japan, Poland, Spain and the United States. Subjects were randomized to receive izokibep or placebo once weekly (QW) through Week 15 (Period 1). Then, all subjects received izokibep QW from Week 16 until Week 51 (Period 2). The Sponsor decided to terminate the study early after all subjects completed (or discontinued) treatment at Week 32. Of the 258 subjects assigned to placebo QW group (129 subjects) or izokibep 160 mg QW group (129 subjects), all received study treatment. A total of 212 subjects completed Period1 in placebo QW group (109 subjects) and the izokibep 160 mg QW group (103 subjects). A total of 28 subjects completed the study in placebo-izokibep 160 mg QW group (19 subjects) and the izokibep 160 mg QW group (9 subjects). Among the 230 subjects who discontinued the study, the most frequently reported reason was study termination by the sponsor in both the placebo-izokibep 160 mg QW group (69 subjects) and the izokibep 160 mg QW group (65 subjects). 29 subjects in the placebo-Izokibep 160 mg QW group and 37 subjects in the izokibep 160 mg QW group discontinued the study due to withdrawal by subject, and 12 subjects in the placebo-Izokibep 160 mg QW group and 18 subjects in the izokibep 160 mg QW group discontinued the study due to lost to follow-up.

In period 1 (up to week 16), treatment-emergent adverse events were reported in 107 subjects (82.9%) in the izokibep 160 mg QW group and 76 subjects (58.9%) in the placebo QW group. The only treatment emergent adverse event experienced by >= 20% of subjects in either treatment group was injection site reaction (66.7% in the izokibep 160 mg QW group and 7.8% in the placebo QW group). Treatment-emergent adverse events led to discontinuation of study treatment in 10 subjects (7.8%) in the izokibep 160 mg QW group and 5 subjects (3.9%) in the placebo QW group. There were no deaths (Grade 5) or life-threatening (Grade 4) events and few subjects experienced a severe (Grade 3) treatment emergent adverse event. Serious treatment-emergent adverse events were reported in 1 subject (0.8%) in the izokibep 160 mg QW group and 5 subjects (3.9%) in the placebo QW group. Serious treatment emergent adverse events were assessed as related to study treatment for 1 subject (0.8%) in the izokibep 160 mg QW group (vasculitis) and 1 subject (0.8%) in the placebo QW group (hepatic enzyme increased and abdominal pain lower). In period 2 (weeks 16+), treatment-emergent adverse events were reported in 66/100 subjects (66.0%) in the izokibep 160 mg QW group and 87/109 subjects (79.8%) in the placebo-izokibep 160 mg QW group. The only treatment emergent adverse event experienced by >= 20% of subjects in either treatment group was injection site reaction (34.0% in the izokibep 160 mg QW group and 60.6% in the placebo-izokibep 160 mg QW group). Treatment-emergent adverse events led to discontinuation of study treatment in 4 subjects (4.0%) in the izokibep 160 mg QW group and 5 subjects (4.6%) in the placebo-izokibep 160 mg QW group. There were no deaths (Grade 5) or life-threatening (Grade 4) events and few subjects experienced a severe (Grade 3) treatment emergent adverse event. Serious treatment-emergent adverse events were reported in 4 subjects (4.0%) in the izokibep 160 mg QW group and 3 subjects (2.8%) in the placebo-izokibep 160 mg QW group. Serious treatment-emergent adverse events were assessed as related to study treatment for no subjects in the izokibep 160 mg QW group and 2 subjects (1.8%) in the placebo-izokibep 160 mg QW group (cellulitis and hepatic enzyme increased). Rates of events of special interest were low across both study periods. In period 1 (up to week 16), no subjects in the izokibep 160 mg QW group experienced events of special interest and 3 subjects (2.3%) in the placebo QW group experienced 3 events of special interest; all were fungal infections. In period 2 (weeks 16+), 1 subject (1.0%) in the izokibep 160 mg QW group experienced 1 event of special interest and 5 subjects (4.6%) in the placebo-izokibep 160 mg QW group experienced 7 events of special interest. Most of these events were fungal infections.

The primary endpoint of percentage of subjects achieving HiSCR75 at week 12, using nonresponse imputation (NRI) and multiple imputation (MI) methods, was statistically significant and achieved by 32.6% of subjects (95% CI, 24.3% to 40.9%) in the izokibep 160 mg QW group and 20.3% of subjects (95% CI, 13.1% to 27.6%) in the placebo QW group (risk difference, 13.0%; 95% CI, 2.2% to 23.7%; standard error [SE], 5.50%; p = 0.0183). Secondary efficacy endpoints that were also statistically significant for comparisons of izokibep 160 mg QW versus placebo QW at week 12, using NRI and MI methods, were HiSCR90, HiSCR100, HiSCR50, Dermatology Life Quality Index total score, AN count of 0, 1, or 2 among subjects with baseline Hurley stage II, and a >= 3-point reduction in Skin Pain numeric rating scale (NRS) score among subjects with a score of >= 4 at baseline. The percentage of subjects who experienced HS flare through 12 weeks of treatment was not statistically significant for izokibep 160 mg QW versus placebo. The percentage of subjects achieving HiSCR90 at week 12 was achieved by 24.3% of subjects (95% CI, 16.7% to 31.9%) in the izokibep 160 mg QW group and 9.2% of subjects (95% CI, 3.8% to 14.5%) in the placebo QW group (risk difference, 15.8%; 95% CI, 6.7% to 25.0%; SE, 4.67%; p = 0.0007). The percentage of subjects achieving HiSCR100 at week 12 was achieved by 21.4% of subjects (95% CI, 14.2% to 28.7%) in the izokibep 160 mg QW group and 7.3% of subjects (95% CI, 2.5% to 12.2%) in the placebo QW group (risk difference, 14.7%; 95% CI, 6.1% to 23.4%; SE, 4.40%; p = 0.0008). The percentage of subjects achieving HiSCR50 at week 12 was achieved by 47.9% of subjects (95% CI, 39.0% to 56.8%) in the izokibep 160 mg QW group and 36.5% of subjects (95% CI, 27.8% to 45.2%) in the placebo QW group (risk difference, 12.3% (95% CI, 0.2% to 24.3%; SE, 6.16%; p=0.0462). The percentage of subjects who experienced one or more (>= 1) disease flare at week 12 was numerically lower in the izokibep 160 mg QW group (28.3% of subjects [95% CI, 20.5% to 36.2%]) compared with the placebo QW group (31.1% of subjects [95% CI, 22.9% to 39.3%]), but it was not significantly different between groups (risk difference, -2.8%; 95% CI, -14.3% to 8.6%; SE, 5.84%; p=0.6285). The LS mean (SE) change from baseline to week 12 in Dermatology Life Quality Index total score was -4.87 (0.536) in the izokibep 160 mg QW group and -2.71 (0.519) in the placebo QW group, (LS mean difference, -2.16; 95% CI, -3.44 to -0.88; p = 0.0011). The percentage of subjects with baseline Hurley stage II who achieved AN count of 0, 1, or 2 at week 12 was achieved by 49.5% of subjects (95% CI, 38.1% to 61.0%) in the izokibep 160 mg QW group and 25.0% of subjects ( 95% CI, 15.2% to 34.8%) in the placebo QW group (risk difference of 24.6%; 95% CI, 9.6 to 39.7; SE, 7.67%; p = 0.0013). The percentage of subjects with baseline NRS >= 4 achieving at least 3-point reduction at week 12 in numeric rating scale (NRS) patient global assessment of Skin Pain at its worst was achieved by 33.5% of subjects (95% CI, 22.1% to 44.8%) in the izokibep 160 mg QW group and 17.2% of subjects (95% CI, 8.4% to 25.9%) in the placebo QW group (risk difference of 16.3%; 95% CI, 2.1 to 30.6; SE, 7.26%; p = 0.0245).

In conclusion, the primary efficacy endpoint of HiSCR75 at week 12 and several secondary efficacy endpoints at week 12 showed statistically significant improvements with izokibep 160 mg QW treatment versus placebo QW in subjects with moderate to severe HS. Izokibep 160 mg QW treatment generally was tolerable; consistent with prior studies, non-serious mild/moderate injection site reactions were common, especially upon initiation of treatment.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230501

Benner Saskia

ACELYRIN, INC.

4149 Liberty Canyon Rd. Agoura Hills, CA 91301, United States of America

saskia.benner@acelyrin.com

Clinical trial contact

ICON Clinical Research GK

Kyutaromachi 4-chome 1-3, Chuo-ku, Osaka city, Osaka

+81-6-4560-2001

ICONCR-Chiken@iconplc.com

Complete

Dec. 09, 2023

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

General
1.Subject has provided signed informed consent including consenting to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
2.18 to 75 years of age
Type of Subject and Disease Characteristics
3.Diagnosis of HS for >= 6 months prior to first dose of study drug
4.Hidradenitis suppurativa lesions present in >= 2 distinct anatomic areas, one of which is Hurley Stage II or Hurley Stage III
5.A total abscess and inflammatory nodule (AN) count of >= 5 at screening and Day 1 prior to enrollment/randomization
6.Subject must have had an inadequate response to oral antibiotics OR exhibited recurrence after discontinuation to, OR demonstrated intolerance to, OR have a contraindication to oral antibiotics for treatment of their HS
7.Must agree to use daily over-the-counter topical antiseptics
8.Subject must be willing to complete a daily skin pain diary
Other protocol defined Inclusion criteria may apply

Medical Conditions
1.Draining fistula count of > 20
2.Outpatient surgery <= 8 weeks prior or inpatient surgery <= 12 weeks prior to enrollment/randomization
3.Other active skin disease or condition that could interfere with study assessments
4.History of active inflammatory bowel disease (IBD) OR symptoms within the last year that may be suggestive of IBD
5.Chronic pain not associated with HS
6.Uncontrolled, clinically significant system disease
7.History of demyelinating disease or neurological symptoms suggestive of demyelinating disease
8.Malignancy within 5 years
9.The subject is at risk of self-harm or harm to others
10.Active infection or history of certain infections
11.Tuberculosis or fungal infection seen on available chest x-ray taken within 3 months prior to first dose of study drug or at screening (Exception: documented evidence of completed treatment and clinically resolved)
12.Known history of human immunodeficiency virus (HIV)
Other protocol defined Exclusion criteria may apply

Both

Moderate to Severe Hidradenitis Suppurativa

Group 1: placebo QW from Day 1/Week 0 to Week 15, then Izokibep 160mg QW from Week 16 to Week 51
Group 2: Izokibep 160 mg QW from Day 1/Week 0 to Week 51

HiSCR75 at Week 16

+81-42-648-5551

Nov. 10, 2023

Canada/France/Germany/Hungary/Poland/Spain/The United States