Pharmacokinetics, Efficacy and Safety of Olokizumab In Patients With Juvenile Idiopathic Arthritis

Официальное название

An Open-label, Multicenter Study of the Pharmacokinetics, Efficacy and Safety of Olokizumab in Pediatric and Adolescent Patients With Active Juvenile Idiopathic Arthritis

Обзор

The primary objective of this study is to evaluate the pharmacokinetics (PK) of olokizumab (OKZ) in patients with polyarticular juvenile idiopathic arthritis aged \>2 and \<18 years in two doses (64 mg or 48 mg every 4 weeks) depending on patient's weight. Secondary objectives are to evaluate the pharmacodynamic (PD) profile, the long-term efficacy and safety of olokizumab in patients with polyarticular juvenile idiopathic arthritis aged \>2 and \<18 years.

Подробное описание

This study is a multicenter, open-label, non-randomized, uncontrolled study with an interim analysis of endpoints after 12 weeks of therapy, a final analysis of endpoints after 24 weeks of therapy, and an additional analysis at the end of all study visits.

The total number of study subjects screened is 71 subjects. Up to 50 patients will begin treatment.

This study includes:

1. A screening period of up to 2 weeks 2. A main period of open label treatment from Week 0 to Week 24 (24 weeks) 3. A period of extended open label treatment from Week 24 to Week 164 (140 weeks) 4. Safety follow-up period from Week 165 to Week 186 (22 weeks)

The total study duration for patients is approximately 188 weeks (including the screening period).

Вмешательства

• Препарат OKZ q4w
  Subcutaneous (SC) injections of OKZ every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection
• Препарат OKZ q4w
  SC injections of OKZ 48 mg every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection

Первичные конечные точки

• Olokizumab Cmax (W24) (maximum concentration) over 24 weeks [Срок оценки: 24 weeks]
• Olokizumab area under the concentration-time curve (AUC0-W24) over 24 weeks [Срок оценки: 24 weeks]

Вторичные конечные точки (7)

• Minimum drug concentration at steady state (Ctrough,ss) [Срок оценки: 24 weeks]
• Maximum concentration (Cmax) of olokizumab after the first administration [Срок оценки: 4 weeks]
• Time to reach maximum concentration (tmax) of olokizumab after the first administration [Срок оценки: 4 weeks]
• The area under the concentration-time curve (AUCtau) of olokizumab over the study period [Срок оценки: 12, 24, 72 weeks]
• Concentration before the next dose of olokizumab (Ctrough) [Срок оценки: 12, 24, 72 weeks]
• Time to steady state (tss) [Срок оценки: 12, 24, 72 weeks]
• Area under the concentration-time curve in the steady state (AUCss) [Срок оценки: 24, 72 weeks]

Критерии участия

Критерии включения

• Study informed consent form voluntarily and independently signed by patient legal representative
• Study assent form voluntarily and independently signed by minor study subject (patient)
• Male or female patients aged ≥12 and <18 years (cohort 1 - subgroup A) or >2 and <12 years (cohort 1 - subgroup B) or >2 and <18 years (cohort 2) at the time of screening initiation and on Day 0
• Body weight at the start of screening and on Day 0 ≥45 kg (cohort 1 - subgroup A) or ≥30 and <45 kg (cohort 1 - subgroup B) or ≥18 and <30 kg (cohort 2)
• A reliable diagnosis of juvenile idiopathic arthritis (JIA) according to the JIA International League of Associations for Rheumatology (ILAR) 1 criteria with onset before the age of 16 years:

• Seropositive or seronegative polyarthritis (pJIA) ≥3 months before screening, or
• Systemic JIA (sJIA) for ≥3 months before screening, provided that joint symptoms persist without active systemic manifestations for ≥3 months before screening, or
• Extended oligoarticular JIA (оJIA) ≥3 months before screening
• American College of Radiology (ACR) criteria of active polyarthritis are met: 5 or more active joints at screening and on Day 0
• C-reactive protein (CRP) level on screening or in anamnesis, not associated with alternative causes of increase other than the activity of the underlying disease, ≥6 mg/l
• Intolerance or failure of methotrexate in the dose of ≥15 mg/m\^2/week (or less, in a case of documented intolerance of higher doses) for ≥3 months in medical history

Критерии исключения

• Prior use of any drug that acts directly on IL-6 or IL-6R
• If methotrexate is administered - any change in dose or in a formulation within 6 weeks prior to Day 0
• Previous therapy with marketed or experimental conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs) within less than 5 elimination half-lives
• Use of oral steroids in the doses above 0.2 mg/kg or 10 mg/day of prednisolone daily, whatever is lower, or a change in dose within 2 weeks prior to Day 0, or use of parenteral or topical steroids within 4 weeks prior to Day 0
• Change in dose of a non-steroidal anti-inflammatory drug (NSAID) within ≤2 weeks prior to Day 0
• Vaccination with live vaccines within 6 weeks before baseline, or planned vaccination with live vaccines during the study and/or within 6 weeks after the last olokizumab administration
• Active uveitis at screening or uveitis exacerbation within 24 weeks before screening
• Laboratory abnormalities (creatinine ≥1 mg/dL (88 mM) for children aged 12 or ≥1.2 mg/dL (106 mM) for children aged 13 and older; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5 х upper limit normal (ULN); platelets <180,000/mm\^3; white blood count (WBC) <4000/mm\^3; neutrophils <2000/mm\^3; hemoglobin ≤80 g/L
• Exclusion criteria related to past or current infection other than tuberculosis
• Suspected or confirmed current tuberculosis (TB) infection, history of an active or latent TB infection
• Active course of a disease associated with formation of intestinal diverticula, or any other symptomatic gastrointestinal disease that may increase risk of perforation; or a history of diverticulitis or perforation; or concurrent Crohn's disease or ulcerative colitis
• Concurrent heart failure New York Heart Association (NYHA) III or IV functional class
• In patients with diabetes mellitus - HbA1c > 7% within the last 3 months (non-controlled diabetes mellitus)
• Patients with Steinbrocker class IV functional impairment
• Presence of systemic autoimmune or autoinflammatory disease, except JIA, or chronic autoimmune hepatitis or diseases of the primary immunodeficiencies group
• Patients with history of macrophage activation syndrome episodes
• Exclusion criteria related to concurrent diseases and conditions that may increase potential risk related to participation in the study and study drug exposure
• Known hypersensitivity to any component of the study drug
• Pregnant or breast-feeding female participants or planned pregnancy
• Other protocol-defined non-inclusion criteria apply

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 14 центров

• Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical U — Kazan'
• Federal State Budgetary Scientific Institution "V.A. Nasonova Research Institute of Rheuma — Moscow
• State Budgetary Institution of Healthcare of the City of Moscow "Morozovskaya Children's C — Moscow
• Federal State Autonomous Educational Institution of Higher Education First Moscow State Me — Moscow
• Federal State Autonomous Institution "National Medical Research Center for Children's Heal — Moscow
• Limited Liability Company "Healthy Family Medical Center" — Novosibirsk
• Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical — Rostov-on-Don
• LLC "Medical Technologies" — Saint Petersburg
• … и ещё 6 центров

Идентификаторы

NCT: NCT07517575 · CL04041182

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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