Psoriatic Arthritis Study of Izokibep

Phase 2

Terminated

• Conditions: Psoriatic Arthritis
• Interventions: Drug: Izokibep; Drug: Placebo to izokibep

• Registration Number: NCT05623345
• Lead Sponsor: ACELYRIN Inc.

Brief Summary

Izokibep is a potent and selective inhibitor of interleukin (IL)-17A that is being developed for treatment of psoriatic arthritis (PsA).

This study will evaluate the efficacy of izokibep in subjects with PsA.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-13
• Study First Submitted QC: 2022-11-13
• Study Start: 2022-11-21
• Study First Posted: 2022-11-21
• Primary Completion: 2023-11-30
• Study Completion: 2024-08-08
• Disposition First Posted: 2024-10-18
• Status Verified: 2024-11
• Disposition First Submitted: 2024-11-25
• Results First Submitted: 2025-05-07
• Results First Submitted QC: 2025-05-22
• Last Update Submitted: 2025-05-22
• Results First Posted: 2025-05-23
• Last Update Posted: 2025-05-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 351

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.
• Subject must be ≥18 (or the legal age of consent in the jurisdiction in which the study is taking place) and ≤75 years of age, at the time of signing the informed consent.

Type of Subject and Disease Characteristics

• Clinical diagnosis of psoriatic arthritis (PsA) with symptom onset at least 6 months prior to first dose of study drug and fulfillment of the ClASsification for Psoriatic ARthritis (CASPAR) criteria at Screening.

• Active PsA defined as ≥3 tender joints (based on 68 joint counts) and ≥3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits

• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) negative at screening.

• Subject must have had an inadequate response, intolerance, or contraindication to at least one of the following:

  1. nonsteroidal anti-inflammatory drug (NSAID)
  2. conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARD) (i.e. methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine A)
  3. tumor necrosis factor-alpha inhibitor(s) (TNFi) (e.g. adalimumab, infliximab, etanercept, golimumab, certolizumab).

• For subjects using methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, or apremilast, treated for ≥3 months and a stable dose (not to exceed 25 mg methotrexate per week, 20 mg leflunomide per day, sulfasalazine 3 g per day, hydroxychloroquine 400 mg per day, or apremilast 60 mg per day) for ≥4 weeks prior to first dose of study drug.

• For subjects using corticosteroids, must have been on a stable dose and regimen and not to exceed 7.5 mg per day of prednisone (or other corticosteroid equivalent to 7.5 mg per day of prednisone) for ≥4 weeks prior to first dose of study drug.

• Subjects using NSAIDs, or low potency opioid medications (tramadol, paracetamol in combination with hydrocodone or with codeine) must have been on a stable dose and regimen for ≥2 weeks prior to first dose of study drug.

Other Inclusions

• No known history of active tuberculosis (TB).
• Subject has a negative TB test at screening

Exclusion Criteria

Disease-related Medical Conditions

• Any history or current confirmed diagnosis of inflammatory bowel disease (IBD)

OR

• Any of the following symptoms (of unknown etiology) or any signs or symptoms within the last year that in the opinion of the Investigator may be suggestive of IBD, with fecal calprotectin ≥ 500 μg/g; OR if fecal calprotectin >150 to <500 μg/g without confirmed approval from a GI consult that an IBD diagnosis is clinically unlikely when the following clinical signs and symptoms are present:

  1. prolonged or recurrent diarrhea
  2. prolonged or recurrent abdominal pain
  3. blood in stool

• History of fibromyalgia, or any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than psoriatic arthritis (PsA) (including, but not limited to rheumatoid arthritis, gout, connective tissue diseases). Prior history of axial spondyloarthritis or fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis was made incorrectly. Prior history of reactive arthritis or axial spondyloarthritis is permitted if an additional diagnosis of PsA is made. Chronic osteoarthritis symptoms that in the Investigator's opinion may interfere with study assessments.

• Uncontrolled, clinically significant system disease

• Malignancy within 5 years

• Severe, uncontrolled, medically unstable mood disorder, such as severe depression.

• History or evidence of any clinically significant disorder (including psychiatric), condition, or disease that, in the opinion of the investigator, may pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

• Active infection or history of certain infections

• Candida infection requiring systemic treatment within 3 months prior to first dose of study drug.

• 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).

• Known history of human immunodeficiency virus (HIV) or positive HIV test at screening.

Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 4	Placebo to izokibep	Izokibep Dose 3 from Day 1/Week 0 to Week 51
Group 4	Izokibep	Izokibep Dose 3 from Day 1/Week 0 to Week 51
Group 1	Izokibep	Placebo from Day 1/Week 0 to Week 15, then izokibep from Week 16 to Week 51
Group 1	Placebo to izokibep	Placebo from Day 1/Week 0 to Week 15, then izokibep from Week 16 to Week 51
Group 2	Izokibep	Izokibep Dose 1 from Day 1/Week 0 to Week 51
Group 3	Izokibep	Izokibep Dose 2 from Day 1/Week 0 to Week 51
Group 3	Placebo to izokibep	Izokibep Dose 2 from Day 1/Week 0 to Week 51

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16	Week 16	ACR50 is a clinical trial measure for PsA, indicating a 50% improvement in symptoms. To qualify, participants must show a 50% reduction in tender and swollen joint counts plus improvements in three of five additional criteria, including pain, global assessments, physical function, and inflammatory markers. ACR50 is binary-patients either meet it or not.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16	Baseline and Week 16	PASI is a tool used in clinical trials to measure the severity and extent of psoriasis. Scores range from a minimum of 0 to a maximum of 72, with higher scores indicating more severe disease.
Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16	Baseline and Week 16	LEI is a clinical tool used to assess enthesitis in conditions like psoriatic arthritis and spondyloarthritis. It evaluates six sites: bilateral lateral epicondyles, medial femoral condyles, and achilles tendons. Each site is scored 0 (no pain) or 1 (pain on pressure), with a total score ranging from a minimum of 0 to a maximum of 6, where higher scores indicate more severe enthesitis.
Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16	Week 16	A participants was classified as being in MDA when at least five of the following seven criteria were met: * Tender joint count based on 68 joints (TJC68) ≤ 1; * Swollen joint count based on 66 joints (SJC66) ≤ 1; * PASI ≤ 1 or BSA ≤ 3%; * Participant's Pain Assessment (Visual Analogue Scale \[VAS\]) ≤ 15 mm; * Participant's Global Activity VAS ≤ 20 mm (corresponding to participant's Global Assessment of Disease Activity); * Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ 0.5; * Tender enthesitis points ≤ 1 out of 6 sites assessed by the LEI.
Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16	Week 16	ACR20 is a clinical trial measure for PsA, indicating a 20% improvement in symptoms. To qualify, participants must show a 20% reduction in tender and swollen joint counts plus improvements in three of five additional criteria, including pain, global assessments, physical function, and inflammatory markers. ACR20 is binary-patients either meet it or not.
Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16	Week 16	The PsAID consists of nine items, each scored on a numeric rating scale (0-10), covering key aspects of disease burden, including pain, fatigue, skin problems, work/leisure activities, functional capacity, sleep disturbance, anxiety, coping, and social participation. The total score is calculated as a weighted sum of these individual items, with higher scores indicating a greater impact of the disease. The minimum score is 0 (no disease impact), while the maximum is 10 (worst possible disease impact). Reaching an improvement was considered an increase of 3 units from baseline score.
Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16	Baseline and Week 16	The HAQ-DI consists of 20 questions divided into eight categories: dressing, arising, eating, walking, hygiene, reaching, grip, and other activities. Each item is scored on a scale from 0 to 3, where 0 = no difficulty, 1 = some difficulty, 2 = much difficulty, and 3 = unable to perform. The final HAQ-DI score is calculated as the average of the highest scores in each category, resulting in a range from 0 (no disability) to 3 (severe disability). Higher scores indicate greater functional impairment. A negative change indicates an improvement in functional impairment.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1	Up to Week 16, or 4 weeks after participant's last dose in case of treatment discontinuation	An AE was any untoward medical occurrence in a participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received study treatment. Clinically significant changes in vital signs, electrocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs.; TEAEs were considered serious if they led to death, were life-threatening, required hospitalization or its prolongation, caused disability, resulted in congenital anomalies or were considered medically important.; The events of special interest monitored were : candida infection; inflammatory bowel disease; suicidal ideation; malignancies; major adverse cardiovascular and cerebrovascular events (cerebrovascular accident and transient ischemic attack, nonfatal myocardial infarction or unstable angina, cardiovascular death); tuberculosis; infections (opportunistic, serious, or fungal); cytopenia; systemic hypersensitivity reactions.
Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2	First dose of study treatment on or after Week 16 up to Week 55	An AE was any untoward medical occurrence in a participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received study treatment. Clinically significant changes in vital signs, electrocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs.; TEAEs were considered serious if they led to death, were life-threatening, required hospitalization or its prolongation, caused disability, resulted in congenital anomalies or were considered medically important.; The events of special interest monitored were : candida infection; inflammatory bowel disease; suicidal ideation; malignancies; major adverse cardiovascular and cerebrovascular events (cerebrovascular accident and transient ischemic attack, nonfatal myocardial infarction or unstable angina, cardiovascular death); tuberculosis; infections (opportunistic, serious, or fungal); cytopenia; systemic hypersensitivity reactions.
Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result	Baseline to Week 65	Blood samples were collected at different timepoints throughout the study. ADA is considered "Positive" if any titer value is available.

Trial Locations

Locations (2)

Clinical Research Site; 🇪🇸 Sevilla, Spain

Clinical Research Site (003); 🇭🇺 Budapest, Hungary