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
Arthritis, Rheumatoid
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring inadequate responders, moderate to severe, Rheumatoid Arthritis
Eligibility 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.
- Treated with a biological disease-modifying anti-rheumatic drug (bDMARDs) OR Janus kinase inhibitor (JAKi) therapy for RA for ≥ 3 months and had inadequate response or had to discontinue bDMARD 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 ≥ 5 mg/L (by central laboratory);
- 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 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)
Exclusion Criteria:
- Prior exposure to any other anti-CD40/CD40L agent.
- Prior treatment failure, inadequate response, or intolerance to 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.
- 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.
Sites / Locations
- Pinnacle Research Group, LLCRecruiting
- Carewell Arthritis CenterRecruiting
- Attune Health Research Inc.Recruiting
- Wallace Rheumatic Studies Center, LLC
- Medvin Clinical ResearchRecruiting
- TriWest Research AssociatesRecruiting
- Medvin Clinical ResearchRecruiting
- Inland Rheumatology Clinical TrialsRecruiting
- Medvin Clinical ResearchRecruiting
- International Medical ResearchRecruiting
- Sweet Hope Research Specialty, Inc.Recruiting
- San Marcus Research Clinic, Inc.Recruiting
- Millennium ResearchRecruiting
- West Broward Rheumatology Associates, Inc.Recruiting
- Center for Advanced Research & Education
- Graves Gilbert ClinicRecruiting
- Bluegrass Community Research, Inc
- Accurate Clinical Research, Inc.Recruiting
- Johns Hopkins University - Johns Hopkins Arthritis CenterRecruiting
- SUNY Downstate Medical Center
- Northwell Health, Division of RheumatologyRecruiting
- Altoona Center for Clinical ResearchRecruiting
- West Tennessee Research InstituteRecruiting
- Saint Francis Hospital- MemphisRecruiting
- Arthritis and Rheumatology Research InstituteRecruiting
- Trinity Universal Research AssocRecruiting
- Arthritis & Osteoporosis Center of Coastal BendRecruiting
- Corpus Christi RheumatologyRecruiting
- Dallas Fort Worth Clinical Research Associates
- Southwest Rheumatology Research LLCRecruiting
- DM Clinical ResearchRecruiting
- Rheumatology Clinic of HoustonRecruiting
- Rheumatology and Pulmonary ClinicRecruiting
- UMHAT "Dr. Georgi Stranski"Recruiting
- Medical center "Artmed" LTDRecruiting
- UMHAT Sveti Ivan RilskiRecruiting
- Vesalion s.r.o.Recruiting
- CCR Czech a.s.,Recruiting
- Revmatologicky UtsavRecruiting
- Medical Plus S.R.O.Recruiting
- Aleksandre Aladashvili Clinic LLCRecruiting
- LTD Israel-Georgian Medical Research Clinic HelsicoreRecruiting
- JSC Evex HospitalsRecruiting
- LTD Georgian-Dutch HospitalRecruiting
- Universitätsklinikum FreiburgRecruiting
- University Hospital Cologne AöRRecruiting
- Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai KozpontRecruiting
- Qualiclinic Ltd (Qualiclinic Inc)Recruiting
- Magyar Honvedseg Egeszsegugyi KozpontRecruiting
- Debreceni Egyetem Klinikai KozpontRecruiting
- Porcika KlinikaRecruiting
- Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi OktatokorhazRecruiting
- Vita Verum Medical EgeszsegugyRecruiting
- Centrum Kliniczno-BadawczeRecruiting
- Silmedic sp. z o.o.Recruiting
- NZOZ Lecznica MAK-MED s.c.Recruiting
- Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel HrycajRecruiting
- RCMed Oddzial SochaczewRecruiting
- Centrum Medyczne Reuma ParkRecruiting
- Clinresco Centres (Pty) LtdRecruiting
- Jacaranda HospitalRecruiting
- Umhlanga Hospital Medical CenterRecruiting
- Panorama Medical CentreRecruiting
- Winelands Medical Research CenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Cohort 1 KPL-404
Cohort 1 Placebo
Cohort 2 KPL-404
Cohort 2 Placebo
Cohort 3 KPL-404
Cohort 3 KPL-404 and Placebo
Cohort 3 Placebo
Cohort 4 KPL-404
Cohort 4 Placebo
KPL-404 2mg/kg Subcutaneous (SC) q2wk for 12 weeks
Placebo for KPL-404 SC q2wk for 12 weeks
KPL-404 5mg/kg SC q2wk for 12 weeks
Placebo for KPL-404 SC q2wk for 12 weeks
KPL-404 5mg/kg SC qwk for 12 weeks
KPL-404 5mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
Placebo for KPL-404 SC qwk for 12 weeks
KPL-404 SC q4wk for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at weeks 4 and 8.
Placebo for KPL-404 SC q4wk for 12 weeks