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

  • End date
    Jun 2, 2024
  • participants needed
  • sponsor
    Kiniksa Pharmaceuticals, Ltd.
Updated on 2 October 2023
certolizumab pegol
rheumatoid factor
cyclic citrullinated peptide antibody


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


This is a 28-week (up to 4-week screening period, 12-week treatment period, and 12-week safety follow-up period), multicenter, randomized, double-blind, placebo-controlled, multiple dose, proof-of-concept study with PK lead-in designed to assess the safety, PK, efficacy and PD of KPL-404 in subjects with moderate to severe, active Rheumatoid Arthritis (RA) who have an inadequate response to or are intolerant to a Janus kinase inhibitor (JAKi) AND/OR at least one biologic disease-modifying anti-rheumatic drug (bDMARD). The objectives of the study are to evaluate safety, efficacy, and PD of KPL-404 compared with placebo across the estimated therapeutic range and to characterize PK across varying dose levels of KPL-404.

Condition Arthritis, Rheumatoid
Treatment Placebo, KPL-404
Clinical Study IdentifierNCT05198310
SponsorKiniksa Pharmaceuticals, Ltd.
Last Modified on2 October 2023


Yes No Not Sure

Inclusion Criteria

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
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
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
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)
Has completed a locally approved authorized COVID-19 vaccine regimen according to
Documented seropositivity for serum Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA) (>ULN) at screening or by prior laboratory evaluation
local guidance at least 3 weeks before the first dose of the Investigational
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)

Exclusion Criteria

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
History of thromboembolic event or a significant risk of future thromboembolic events
Injectable corticosteroids (including intra-articular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 8 weeks prior to randomization
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 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 any of the following cardiovascular conditions
Moderate to severe congestive heart failure (New York Heart Association class III or IV)
Clinically significant active infection including signs/symptoms suggestive of infection, any significant recurrent or chronic infection, or subjects at a high risk of infection
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
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