Clinical trial NCT05623345: Psoriatic Arthritis Study of Izokibep
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Psoriatic Arthritis
Keywords: psoriatic arthritis (PsA)
psoriasis
inflammatory arthritis
enthesitis
Lead sponsor: ACELYRIN Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-21
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: 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
timeFrame: Baseline and Week 16
measure: Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16
timeFrame: Baseline and Week 16
measure: Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16
timeFrame: Week 16
measure: Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16
timeFrame: Week 16
measure: Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16
timeFrame: Week 16
measure: Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16
timeFrame: Baseline and Week 16
measure: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1
timeFrame: Up to Week 16, or 4 weeks after participant's last dose in case of treatment discontinuation
measure: Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2
timeFrame: First dose of study treatment on or after Week 16 up to Week 55
measure: Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result
timeFrame: Baseline to Week 65
Other outcomes:
Locations:
city: Flagstaff
country: United States
facility: Clinical Research Site
state: Arizona
city: Glendale
country: United States
facility: Clinical Research Site
state: Arizona
city: Mesa
country: United States
facility: Clinical Research Site
state: Arizona
city: Phoenix
country: United States
facility: Clinical Research Site
state: Arizona
city: Tucson
country: United States
facility: Clinical Research Site
state: Arizona
city: Jonesboro
country: United States
facility: Clinical Research Site
state: Arkansas
city: Encino
country: United States
facility: Clinical Research Site
state: California
city: Fountain Valley
country: United States
facility: Clinical Research Site
state: California
city: Fullerton
country: United States
facility: Clinical Research Site
state: California
city: Los Angeles
country: United States
facility: Clinical Research Site
state: California
city: Rancho Mirage
country: United States
facility: Clinical Research Site
state: California
city: Sacramento
country: United States
facility: Clinical Research Site
state: California
city: San Diego
country: United States
facility: Clinical Research Site
state: California
city: Santa Monica
country: United States
facility: Clinical Research Site
state: California
city: Upland
country: United States
facility: Clinical Research Site
state: California
city: Aventura
country: United States
facility: Clinical Research Site
state: Florida
city: Clearwater
country: United States
facility: Clinical Research Site
state: Florida
city: Kissimmee
country: United States
facility: Clinical Research Site
state: Florida
city: New Port Richey
country: United States
facility: Clinical Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Clinical Research Site
state: Florida
city: Sarasota
country: United States
facility: Clinical Research Site
state: Florida
city: Gainesville
country: United States
facility: Clinical Research Site
state: Georgia
city: Hinsdale
country: United States
facility: Clinical Research Site
state: Illinois
city: Orland Park
country: United States
facility: Clinical Research Site
state: Illinois
city: Skokie
country: United States
facility: Clinical Research Site
state: Illinois
city: Lexington
country: United States
facility: Clinical Research Site
state: Kentucky
city: Grand Blanc
country: United States
facility: Clinical Research Site
state: Michigan
city: Kalispell
country: United States
facility: Clinical Research Site
state: Montana
city: Santa Fe
country: United States
facility: Clinical Research Site
state: New Mexico
city: Hickory
country: United States
facility: Clinical Research Site
state: North Carolina
city: Middleburg Heights
country: United States
facility: Clinical Research Site
state: Ohio
city: Corvallis
country: United States
facility: Clinical Research Site
state: Oregon
city: Duncansville
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Jackson
country: United States
facility: Clinical Research Site
state: Tennessee
city: Memphis
country: United States
facility: Clinical Research Site
state: Tennessee
city: Colleyville
country: United States
facility: Clinical Research Site
state: Texas
city: Irving
country: United States
facility: Clinical Research Site
state: Texas
city: Mesquite
country: United States
facility: Clinical Research Site
state: Texas
city: Seattle
country: United States
facility: Clinical Research Site
state: Washington
city: Beckley
country: United States
facility: Clinical Research Site
state: West Virginia
city: Bourgas
country: Bulgaria
facility: Clinical Research Site
city: Pleven
country: Bulgaria
facility: Clinical Research Site
city: Ruse
country: Bulgaria
facility: Clinical Research Site
city: Sofia
country: Bulgaria
facility: Clinical Research Site
city: Sydney
country: Canada
facility: Clinical Research Site
state: Nova Scotia
city: Windsor
country: Canada
facility: Clinical Research Site
state: Ontario
city: Québec
country: Canada
facility: Clinical Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Clinical Research Site
state: Quebec
city: Saskatoon
country: Canada
facility: Clinical Research Site
state: Saskatchewan
city: Ostrava
country: Czechia
facility: Clinical Research Site
city: Praha
country: Czechia
facility: Clinical Research Site
city: Zlin
country: Czechia
facility: Clinical Research Site
city: Frankfurt am Main
country: Germany
facility: Clinical Research Site
city: Hamburg
country: Germany
facility: Clinical Research Site
city: Budapest
country: Hungary
facility: Clinical Research Site
city: Budapest
country: Hungary
facility: Clinical Research Site (003)
city: Kalocsa
country: Hungary
facility: Clinical Research Site
city: Székesfehérvár
country: Hungary
facility: Clinical Research Site
city: Veszprém
country: Hungary
facility: Clinical Research Site
city: Bialystok
country: Poland
facility: Clinical Research Site
city: Białystok
country: Poland
facility: Clinical Research Site
city: Bydgoszcz
country: Poland
facility: Clinical Research Site
city: Elbląg
country: Poland
facility: Clinical Research Site
city: Kraków
country: Poland
facility: Clinical Research Site
city: Poznań
country: Poland
facility: Clinical Research Site
city: Poznań
country: Poland
facility: Clinical Research Site
city: Warszawa
country: Poland
facility: Clinical Research Site
city: Warszawa
country: Poland
facility: Clinical Research Site
city: Alcobendas
country: Spain
facility: Clinical Research Site
city: Santiago De Compostela
country: Spain
facility: Clinical Research Site
city: Sevilla
country: Spain
facility: Clinical Research Site
Study officials:
affiliation: ACELYRIN Inc.
name: Shepard Mpofu, MD, Clinical Development
role: STUDY_DIRECTOR
References: