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

Completed · Phase 2 · Has a placebo group

Conditions studied: Arthritis, Rheumatoid

In brief

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

Key facts

Study ID

NCT05198310

Run by

Kiniksa Pharmaceuticals, Ltd.

People needed

145

Starts

2021-12-14

Expected to finish

2024-05-06

Last updated by the study team

2025-07-22

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Body weight ≥ 40 to ≤ 140 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.
• Treated with a biological disease-modifying anti-rheumatic drug (bDMARDs) AND/OR Janus kinase inhibitor (JAKi) therapy for RA for ≥ 3 months and had inadequate response or had to discontinue bDMARD AND/OR JAKi therapy due to intolerance or toxicity, regardless of treatment duration.
• 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.
• 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).
• 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:
• Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits;
• Level of high-sensitivity C-reactive protein ≥ 3 mg/L (by central laboratory);
• Documented seropositivity for serum Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA) (>ULN) at screening or by prior laboratory evaluation.
• Has completed a locally approved authorized COVID-19 vaccine regimen according to local guidance at least 3 weeks before the first dose of the Investigational Product.
• 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:
• ≥ 4 weeks for etanercept;
• ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and sarilumab;
• ≥ 1 year for rituximab;
• ≥ 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)

You may not qualify if…

• Prior exposure to any other anti-CD40/CD40L agent.
• Inadequate response to 5 or more classes of advanced targeted therapies (bDMARD or tsDMARD; e.g., TNF inhibitors, IL-6 receptor inhibitors, T-cell costimulatory inhibitors, anti-CD-20 antibodies, JAK inhibitors). This does not include prior discontinuation due to drug intolerance.
• Injectable corticosteroids (including intra-articular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 8 weeks prior to randomization.
• History of any arthritis with onset prior to age 16 years or current diagnosis of inflammatory joint disease other than RA (Current diagnosis of secondary Sjogren's syndrome is permitted).
• History of thromboembolic event or a significant risk of future thromboembolic events
• Clinically significant active infection including signs/symptoms suggestive of infection, any significant recurrent or chronic infection, or subjects at a high risk of infection
• 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:
• Moderate to severe congestive heart failure (New York Heart Association class III or IV);
• Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting;
• 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.

Where it is running

• Carewell Arthritis Center — Apple Valley, California, United States
• Medvin Clinical Research — Covina, California, United States
• Inland Rheumatology Clinical Trials — Upland, California, United States
• Medvin Clinical Research — Whittier, California, United States
• International Medical Research — Daytona Beach, Florida, United States
• Sweet Hope Research Specialty, Inc. — Hialeah, Florida, United States
• San Marcus Research Clinic, Inc. — Miami Lakes, Florida, United States
• Millennium Research — Ormond Beach, Florida, United States
• West Broward Rheumatology Associates, Inc. — Tamarac, Florida, United States
• Paramount Medical Research & Consulting, LLC — Middleburg Heights, Ohio, United States
• Altoona Center for Clinical Research — Duncansville, Pennsylvania, United States
• Saint Francis Hospital- Memphis — Memphis, Tennessee, United States
• Arthritis and Rheumatology Research Institute — Allen, Texas, United States
• Trinity Universal Research Assoc — Carrollton, Texas, United States
• Arthritis & Osteoporosis Center of Coastal Bend — Corpus Christi, Texas, United States
• Southwest Rheumatology Research LLC — Mesquite, Texas, United States
• DM Clinical Research — Tomball, Texas, United States
• Rheumatology Clinic of Houston — Tomball, Texas, United States
• Rheumatology and Pulmonary Clinic — Beckley, West Virginia, United States
• Medical center "Artmed" LTD — Plovdiv, Bulgaria
• Vesalion s.r.o. — Ostrava, Czechia
• Revmatologicky Utsav — Prague, Czechia
• Medical Plus S.R.O. — Uherské Hradiště, Czechia
• Aleksandre Aladashvili Clinic LLC — Tbilisi, Georgia
• LTD Israel-Georgian Medical Research Clinic Helsicore — Tbilisi, Georgia

Full record on ClinicalTrials.gov

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