Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor

• Status: Recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Phase 2 study of the safety, tolerability, PK, and efficacy of KPL-404 in subjects with moderate to severe Rheumatoid Arthritis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kiniksa Pharmaceuticals, Ltd.

Criteria

Inclusion Criteria:

• Body weight ≥ 40 to ≤ 100 kg for all cohorts.

• Diagnosis of RA for ≥ 3 months fulfilling the 2010 American College of Rheumatology (ACR)/European Union League Against Rheumatism (EULAR) classification criteria for RA and that is categorized as ACR RA functional Class 1-3.

• Currently receiving conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks before the first dose of investigational product.

1. The following csDMARDs are allowed: oral or parenteral methotrexate ([MTX]; 7.5 to 25 mg/week), sulfasalazine (≤ 3000 mg/day), hydroxychloroquine (≤ 400 mg/day), chloroquine (≤ 250 mg/day), and leflunomide (≤ 20 mg/day).

2. A combination of up to 2 background csDMARDs is allowed, except the combination of MTX and leflunomide.

• Meets all of the following disease activity criteria:

1. Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits;

2. Level of high-sensitivity C-reactive protein ≥ 5 mg/L (by central laboratory);

3. Seropositivity for serum Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA) at screening, according to the central laboratory's definition of positivity.

• Has completed a locally approved authorized COVID-19 vaccine regimen according to local guidance at least 3 weeks before the first dose of the IP.

• Must have discontinued all bDMARDs or JAKi prior to the first dose of investigational product. The washout period for bDMARDs or JAKi prior to the first dose of investigational product is specified below. For bDMARDs or JAKi not listed below washout should be at least 5 times the mean elimination half-life of a drug:

1. ≥ 4 weeks for etanercept;

2. ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and sarilumab;

3. ≥ 1 year for rituximab;

4. ≥ 2 weeks for JAKi (either investigational or commercially available treatment).

• Voluntarily sign and date an informed consent form approved by independent ethics committee/Institutional Review Board (IRB)

Exclusion Criteria:

• Prior exposure to any other anti-CD40/CD40L agent.

• Prior treatments with both a bDMARD and a JAKi.

• Injectable corticosteroids (including intra-articular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 8 weeks prior to randomization. (Note: Concomitant treatment with nonsteroidal anti-inflammatory drugs, acetaminophen, oral corticosteroids [equivalent to prednisone ≤ 10 mg/day], or inhaled corticosteroids at a stable dose ≥ 4 weeks prior to baseline for stable medical conditions is allowed and should be kept at a stable dose throughout the study.)

• History of any arthritis with onset prior to age 16 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and nonradiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]). Current diagnosis of secondary Sjogren's syndrome is permitted.

• History of thromboembolic event or a significant risk of future thromboembolic events

• History of cancer within the last 5 years from screening, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.

• History of any of the following cardiovascular conditions:

1. Moderate to severe congestive heart failure (New York Heart Association class III or IV);

2. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting;

3. Uncontrolled hypertension as defined by a confirmed systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg.

• Clinically relevant or significant electrocardiogram (ECG) abnormalities, including ECG with QT interval corrected for heart rate (QTc) > 500 msec.