Psoriatic Arthritis Study of Izokibep

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Drug: Izokibep
* Drug: Placebo to izokibep


Participation Criteria
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Eligibility Criteria
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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: nonsteroidal anti-inflammatory drug (NSAID) conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARD) (i.e. methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine A) 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: prolonged or recurrent diarrhea prolonged or recurrent abdominal pain 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Placebo from Day 1/Week 0 to Week 15, then izokibep from Week 16 to Week 51 | Drug: Izokibep<br>* Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)<br>Drug: Placebo to izokibep<br>* Form: Solution for injection Route of administration: Subcutaneous (SC)<br>|
| Experimental: Group 2<br>Izokibep Dose 1 from Day 1/Week 0 to Week 51 | Drug: Izokibep<br>* Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)<br>|
| Experimental: Group 3<br>Izokibep Dose 2 from Day 1/Week 0 to Week 51 | Drug: Izokibep<br>* Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)<br>Drug: Placebo to izokibep<br>* Form: Solution for injection Route of administration: Subcutaneous (SC)<br>|
| Experimental: Group 4<br>Izokibep Dose 3 from Day 1/Week 0 to Week 51 | Drug: Izokibep<br>* Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)<br>Drug: Placebo to izokibep<br>* Form: Solution for injection Route of administration: Subcutaneous (SC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving 50% improvement in American College of Rheumatology (ACR50) |  | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with resolution of enthesitis Leeds Enthesitis Index in subjects with enthesitis (LEI>0) at baseline |  | Week 16 | 
| Proportion of subjects achieving an improvement in Psoriatic Arthritis Impact of Disease (PsAID) of at least 3 units at Week 16 compared to baseline in subjects with PsAID ≥3 at baseline |  | Week 16 | 
| Proportion of subjects achieving minimal disease activity (MDA) |  | Week 16 | 
| Proportion of subjects achieving 90% or greater reduction in Psoriasis Area and Severity Index (PASI) score from baseline (PASI90) at Week 16 in subjects with ≥3% body surface area (BSA) psoriasis at baseline |  | Week 16 | 
| Change in physical function as assessed by Health Assessment Questionnaire - Disability Index (HAQ-DI) change from baseline to Week 16 |  | Week 16 | 
| Proportion of subjects achieving 20% improvement in American College of Rheumatology (ACR20) |  | Week 16 | 
| Incidence of treatment-emergent adverse events (TEAEs) |  | Day 1 to end of treatment; Up to 52 weeks (±3 days) | 
| Incidence of events of interest |  | Screening to Safety Follow-up; Up to 59 weeks (±5 days) | 
| Incidence of serious adverse events (SAEs) |  | Screening to Safety Follow-up; Up to 59 weeks (±5 days) | 
| Incidence of clinically significant changes in laboratory values |  | Screening to End of Study; Up to 65 weeks (±5 days) | 
| Incidence of clinically significant changes in vital signs |  | Screening to Safety Follow-up; Up to 59 weeks (±5 days) | 
| Incidence of treatment-emergent anti-drug antibodies (ADAs) |  | Day 1 to End of Study; Up to 65 weeks (±5 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriatic arthritis (PsA), psoriasis, inflammatory arthritis, enthesitis