A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2b/3 Study to Evaluate the Efficacy and Safety of Izokibep in Subjects With Active Psoriatic Arthritis

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 75 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 351 participants

Study Arms

• Group 1 (EXPERIMENTAL)
  Placebo from Day 1/Week 0 to Week 15, then izokibep from Week 16 to Week 51
• Group 2 (EXPERIMENTAL)
  Izokibep Dose 1 from Day 1/Week 0 to Week 51
• Group 3 (EXPERIMENTAL)
  Izokibep Dose 2 from Day 1/Week 0 to Week 51
• Group 4 (EXPERIMENTAL)
  Izokibep Dose 3 from Day 1/Week 0 to Week 51

Interventions

• DRUG: Izokibep — Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)
• DRUG: Placebo to izokibep — Form: Solution for injection Route of administration: Subcutaneous (SC)

Primary Outcomes

• Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16 (Week 16)

Secondary Outcomes

• 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)
• Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16 (Baseline and Week 16)
• Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16 (Week 16)
• Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16 (Week 16)
• Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16 (Week 16)

Eligibility Criteria

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

Trial Locations

• Clinical Research Site, Flagstaff, Arizona, United States
• Clinical Research Site, Glendale, Arizona, United States
• Clinical Research Site, Mesa, Arizona, United States
• Clinical Research Site, Phoenix, Arizona, United States
• Clinical Research Site, Tucson, Arizona, United States
• Clinical Research Site, Jonesboro, Arkansas, United States
• Clinical Research Site, Encino, California, United States
• Clinical Research Site, Fountain Valley, California, United States
• Clinical Research Site, Fullerton, California, United States
• Clinical Research Site, Los Angeles, California, United States
• ...and 10 more locations

Study Officials

• Shepard Mpofu, MD, Clinical Development — STUDY_DIRECTOR
  ACELYRIN Inc.

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