COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2022-000169-42/HU

Kiniksa Pharmaceuticals, Ltd. - Erica Boswell

ClinicalTrials@Kiniksa.com

2022-10-18

Completed

RCT

Randomized

Parallel

Blind label

multi-center

Treatment

1. Voluntarily sign and date an informed consent form, approved by an Independent Ethics Committee/Institutional Review Board, prior to the initiation of any screening or studyspecific procedures. 2. Adult male or female, age 18 to 80 years of age (inclusive) at the time of signing the informed consent form. 3. Body weight ≥ 40 to ≤ 100 kg for all cohorts. 4. 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. 5. 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. 6. Currently receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks before the first dose of investigational product. a. 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). b. A combination of up to 2 background csDMARDs is allowed, except the combination of MTX and leflunomide. 7. Meets all of the following disease activity criteria: a. Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits, b. Level of high-sensitivity C-reactive protein ≥ 5 mg/L (by central laboratory), c. Seropositivity for serum RF and/or ACPA at screening, according to the central laboratory’s definition of positivity. 8. Has completed a locally approved authorized COVID-19 vaccine regimen according to local guidance at least 3 weeks before the first dose of investigational product. 9. 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: a. ≥ 4 weeks for etanercept, b. ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and sarilumab, c. ≥ 1 year for rituximab, d. ≥ 2 weeks for JAKi (either investigational or commercially available treatment). 10. Must have discontinued all high-potency opiates at least 1 week for prior to the first dose of investigational product. 11. If female, must be either postmenopausal (defined as no menses for 12 months without other medical cause), permanently surgically sterile, or, for women of childbearing potential, must practice at least one highly effective method of contraception that is effective from study Day 1 through at least 30 days after the EOS visit (additional local requirements may apply). Sexually active female subjects must be: Nonpregnant, nonlactating, and having agreed to use a highly effective method of contraception from the screening visit until 30 days after EOS visit. o Note: highly effective methods of contraception include: hormonal contraceptives associated with inhibition of ovulation (stable dose for at least 4 weeks prior to first dose of investigational product) intrauterine device intrauterine system bilateral tubal occlusion vasectomized male partner abstinence from heterosexual intercourse 12. Sexually active male subjects must have documented vasectomy or must agree to use a condom or highly effective method of contraception as defined above with their partners of childbearing potential from first dose of investigational product until 30 days after EOS visit. 13. Male subjects must agree to refrain from donating sperm from first dose until 30 days after the last study drug administration. Female subjects must agree to refrain from donating eggs from first dose of investigational product until 30 days after EOS visit. 14. Female of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) test at the screening visit and negative urine pregnancy test on Day 1.

1. Prior exposure to any other anti-CD40/CD40L agent. 2. Prior treatment failure, inadequate response, or intolerance to both a bDMARD and a JAKi. 3. 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.) 4. Has received any investigational product within 30 days or 5 half-lives if the half-life is known of the investigational product (whichever is longer) before the first dose of investigational product. 5. Concurrent enrollment in another clinical study, with the exception of observational studies. 8. Receipt of live (attenuated) vaccine within the 4 weeks before baseline or expected need of live vaccination during study participation including 4 weeks after the last dose of investigational product. 9. 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. 10. Clinically significant active infection including signs/symptoms suggestive of infection, any significant recurrent or chronic infection (including positive hepatitis C virus antibody), or any episode of infection requiring hospitalization or treatment with IV antibiotics within 12 weeks before screening, or treatment with oral anti-infectives within 14 days prior to the first dose of investigational product. Subjects with any opportunistic infection within 6 months before screening will be excluded from the study. 12. Subjects at a high risk of infection (eg, history of hereditary or acquired immune deficiency disorder), a history of an infected joint prosthesis at any time with that prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections. 13. Subjects testing positive for human immunodeficiency virus infection. HIV test will not be required if a subject had a previously documented negative HIV result within 8 weeks screening. 14. Subjects with chronic active hepatitis B infection as defined below will be excluded from the study: a. Hepatitis B surface antigen positive. b. Hepatitis B anti-core antibody positive but anti-surface antibody negative. 15. Positive (or 2 indeterminate) QuantiFERON® test results (when possible, test should be performed at least 4 weeks after receiving an mRNA COVID-19 vaccine). 16. History of thromboembolic event, a significant risk of future thromboembolic events (defined as a definitive diagnosis of thrombophilia OR an unstable condition associated with an increased incidence of thrombosis, such as atrial fibrillation or presence of antiphospholipid antibodies). All history of thrombosis should be approved by the medical monitor. 17. Laboratory values meeting the following criteria within the screening period (prior to randomization) of investigational product: a. Serum aspartate aminotransferase > 3 × upper limit of normal (ULN), b. Serum alanine aminotransferase > 3 × ULN, c. Total bilirubin > 2 × ULN, d. Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula < 40 mL/min/1.73 m2 , e. Absolute neutrophil count < 1,500/μL, f. Hemoglobin < 9 g/dL, g. Total white blood cell count < 2,500/μL, h. Platelet count < 150,000/μL, i. Absolute lymphocyte count < 800/μL. 19. 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. 21. History of any of the following cardiovascular conditions: a. Moderate to severe congestive heart failure (New York Heart Association class III or IV), b. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, c. Uncontrolled hypertension as defined by a confirmed systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg. 22. Clinically relevant or significant electrocardiogram (ECG) abnormalities, including ECG with QT interval corrected for heart rate (QTc) > 500 msec. 23. Any condition that, in the opinion of the investigator, could interfere with evaluation of the investigational product or interpretation of subject safety or confound the results of the study.

2

Kiniksa Pharmaceuticals, Ltd.

18

100

Bulgaria;Czech Republic;Georgia;Germany;Hungary;Poland;Serbia;South Africa;United States;Bermuda

Moderate/severe disease at enrollment

4: Moderate/severe disease at enrollment

10

Cohorts 1, 2: • Incidence of treatment-emergent adverse events (TEAEs) • Maximum serum concentration (Cmax) • Area under the serum concentration time curve from 0 to the end of the dosing interval (AUC0-t) Cohort 3: •Change from baseline in disease activity score of 28 joints using C-reactive protein (DSA28-CRP) at Week 12.

Declared number of arm (10.0) differs from found arms (2.0)

Phase 2

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