Hidradenitis Suppurativa Phase 2b Pivotal Study of Izokibep

Phase 2

Completed

Conditions: Hidradenitis Suppurativa

Interventions: Drug: Izokibep
Drug: Placebo to izokibep

Registration Number: NCT05355805

Lead Sponsor: ACELYRIN Inc.

Brief Summary: Izokibep is a potent and selective inhibitor of interleukin 17A (IL-17A) that is being developed for treatment of hidradenitis suppurativa (HS).

This study will evaluate the efficacy, safety, and immunogenicity of izokibep administered subcutaneously (SC) in adult subjects with moderate to severe HS.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 176

Inclusion Criteria

General

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.
18 years to 75 years of age

Type of Subject and Disease Characteristics

Diagnosis of hidradenitis suppurativa (HS) for ≥ 1 year prior to first dose of study drug.
Hidradenitis suppurativa lesions present in ≥ 2 distinct anatomic areas , one of which is Hurley Stage II or III.
A total abscess and inflammatory nodule (AN) count of ≥ 5 at screening and Day 1 prior to enrollment/randomization.
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.
Must agree to use daily over-the-counter topical antiseptics.
Subject must be willing to complete a daily skin pain diary.

Exclusion Criteria

Medical Conditions

Draining fistula count of > 20.
Outpatient surgery ≤ 8 weeks prior or inpatient surgery ≤ 12 weeks prior to enrollment/randomization.
Other active skin disease or condition that could interfere with study assessments.
Chronic pain not associated with HS.
Uncontrolled, clinically significant system disease
History of demyelinating disease or neurological symptoms suggestive of demyelinating disease.
Malignancy within 5 years.
The subject is at risk of self-harm or harm to others
Active infection or history of certain infections
Tuberculosis or fungal infection seen on available chest x-ray taken ≤ 3 months of screening or at screening (Exception: documented evidence of completed treatment and clinically resolved).
Known history of human immunodeficiency virus (HIV).

Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A (Open-label) izokibep every week	Izokibep	Participants will receive izokibep every week from Day 1 through Week 31
Part B (Double-blind) izokibep every week	Izokibep	Participants will receive izokibep every week for 31 weeks.
Part B (Double-blind) izokibep every other week	Izokibep	Participants will receive izokibep every other week for 30 weeks.
Part B (Double-blind) placebo every week	Placebo to izokibep	Participants will receive placebo every week up to Week 15, then izokibep from Week 16 to Week 31.
Part B (Double-blind) placebo every other week	Placebo to izokibep	Participants will receive placebo every other week up to Week 14, then izokibep from Week 16 to Week 30.

Primary Outcome Measures

Name	Time	Method
Part A: Number of Participants Who Achieved Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 12	Part A: Baseline to Week 12	HiSCR75 was defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count.
Part B: Number of Participants Who Achieved HiSCR75 at Week 16	Part B: Baseline to Week 16	HiSCR75 was defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count.

Secondary Outcome Measures

Name	Time	Method
Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Part A: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks	An adverse event (AE) referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs)	Baseline, Week 16, Week 32, Week 39	Blood samples were collected at different time points throughout the study.
Part B: Number of Participants Who Achieved HiSCR90 at Week 16	Part B: Baseline to Week 16	HiSCR90 was defined as at least a 90% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count
Part B: Number of Participants Who Achieved HiSCR100 at Week 16	Part B: Baseline to Week 16	HiSCR100 was defined as at least a 100% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count.
Part B: Number of Participants Who Achieved HiSCR50 at Week 16	Part B: Baseline to Week 16	HiSCR50 was defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count
Part B: Percentage of Participants Who Experienced ≥ 1 Disease Flare Through 16 Weeks of Treatment	Part B: Day 1 through to Week 16	A flare was defined as ≥ 25% increase in AN count with a minimum increase of 2 AN relative to baseline. Missing data of abscess and inflammatory nodules counts at scheduled visits are imputed assuming monotone missingness pattern. Predictors in the regression model for missing values at Week 4 are Baseline Hurley stage, baseline abscess count, baseline inflammatory nodule count, baseline draining fistula count, sex, race, age, body mass index (BMI) and prior Biologic/JAK inhibitor use for HS. Predictors in the regression model for missing values after Week 4 are all of these variables, plus counts of abscess, inflammatory nodule, and draining fistula at prior scheduled assessment. Missing flare values in both the placebo and izokibep groups are imputed using observed data from the placebo group only.
Part B: Number of Participants With Hurley Stage II at Baseline Who Achieved AN Count of 0, 1, or 2	Part B: Week 16	The percentage of participants with baseline Hurley Stage II who achieved AN count of 0, 1, or 2 at Week 16. Hurley stages: Stage 1 - solitary or multiple, isolated abscess formation without scarring or sinus tracts Stage 2 - recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation Stage 3 - diffuse or broad involvement, with multiple interconnected sinus tracts and abscesses.
Part B: Number of Participants Who Achieved at Least a 3-Point Reduction From Baseline in Numeric Rating Scale (NRS) in Patient Global Assessment of Skin Pain at Its Worst at Week 16 Among Participants With Baseline NRS ≥ 4	Part B: Baseline to Week 16	The Patient Global Assessment of Skin Pain is a NRS that consists of scores from 0 to 10 with 0 indicating "no skin pain" and 10 indicating "pain as bad as you can imagine".
Part B: Number of Participants With TEAEs of Special Interest	Part B: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks	Adverse events of special interest were adverse events in the following categories: candida infection, inflammatory bowel disease, suicidal ideation, malignancies, major cardiovascular and cerebrovascular events, tuberculosis, infections, cytopenias and hypersensitivity reactions.
Part B: Number of Participants With TEAEs	Part B: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks	An AE referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. SAEs were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Part B: Number of Participants Testing Positive for ADAs	Up to 39 weeks	Blood samples were collected at different time points throughout the study.