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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05198310
Other study ID # KPL-404-C211
Secondary ID 2022-000169-42
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date December 14, 2021
Est. completion date May 2024

Study information

Verified date March 2024
Source Kiniksa Pharmaceuticals, Ltd.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


Description:

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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 145
Est. completion date May 2024
Est. primary completion date February 8, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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. - 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. 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 = 3 mg/L (by central laboratory); 3. 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: 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. - 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: 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
KPL-404
Humanized monoclonal antibody
Placebo
Matching placebo

Locations

Country Name City State
Bulgaria Medical center "Artmed" LTD Plovdiv
Czechia Vesalion s.r.o. Ostrava
Czechia Revmatologicky Utsav Praha 2
Czechia Medical Plus S.R.O. Uherské Hradište
Georgia Aleksandre Aladashvili Clinic LLC Tbilisi
Georgia JSC Evex Hospitals Tbilisi
Georgia LTD Georgian-Dutch Hospital Tbilisi
Georgia LTD Israel-Georgian Medical Research Clinic Helsicore Tbilisi
Hungary Magyar Honvedseg Egeszsegugyi Kozpont Budapest
Hungary Qualiclinic Ltd (Qualiclinic Inc) Budapest
Hungary Porcika Klinika Hódmezovásárhely
Hungary Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Nyíregyháza
Hungary Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Szeged Csongrád
Hungary Vita Verum Medical Egeszsegugy Székesfehérvár
Poland Centrum Kliniczno-Badawcze Elblag
Poland Silmedic sp. z o.o. Katowice
Poland Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel Hrycaj Poznan
Poland RCMed Oddzial Sochaczew Sochaczew
Poland Centrum Medyczne Reuma Park Warszawa
South Africa Panorama Medical Centre Cape Town Western Cape
South Africa Clinresco Centres (Pty) Ltd Kempton Park Gauteng
South Africa Jacaranda Hospital Pretoria Gauteng
South Africa Umhlanga Hospital Medical Center Umhlanga Kwazulu-Natal
United States Arthritis and Rheumatology Research Institute Allen Texas
United States Carewell Arthritis Center Apple Valley California
United States Rheumatology and Pulmonary Clinic Beckley West Virginia
United States Trinity Universal Research Assoc Carrollton Texas
United States Arthritis & Osteoporosis Center of Coastal Bend Corpus Christi Texas
United States Medvin Clinical Research Covina California
United States International Medical Research Daytona Beach Florida
United States Altoona Center for Clinical Research Duncansville Pennsylvania
United States Sweet Hope Research Specialty, Inc. Hialeah Florida
United States Saint Francis Hospital- Memphis Memphis Tennessee
United States Southwest Rheumatology Research LLC Mesquite Texas
United States San Marcus Research Clinic, Inc. Miami Lakes Florida
United States Paramount Medical Research & Consulting, LLC Middleburg Heights Ohio
United States Millennium Research Ormond Beach Florida
United States West Broward Rheumatology Associates, Inc. Tamarac Florida
United States DM Clinical Research Tomball Texas
United States Rheumatology Clinic of Houston Tomball Texas
United States Inland Rheumatology Clinical Trials Upland California
United States Medvin Clinical Research Whittier California

Sponsors (1)

Lead Sponsor Collaborator
Kiniksa Pharmaceuticals, Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Georgia,  Hungary,  Poland,  South Africa, 

Outcome

Type Measure Description Time frame Safety issue
Primary Cohorts 1 and 2: Incidence of Treatment-Emergent Adverse Events (TEAEs) Up to 24 weeks
Primary Cohorts 1 and 2: Maximum Serum Concentration (Cmax) Predose on Days 1-169
Primary Cohorts 1 and 2: Area Under the Curve from Time 0 to the Last Measurable Concentration (AUC0-t) Predose on Days 1-169
Primary Cohort 3 and 4: Change from Baseline in Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) at Week 12 Baseline, Week 12
Secondary Cohorts 1 and 2: Change from Baseline in DAS28-CRP at Week 12 Baseline, Week 12
Secondary Cohort 3 and 4: Incidence of TEAEs Up to 24 weeks
Secondary Cohort 3 and 4: Cmax Predose on Days 1-169
Secondary Cohort 3 and 4: AUC0-t Predose on Days 1-169
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