A Study to Investigate Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Systemic Lupus Erythematosus

Официальное название

A Multicenter, Open-Label, Phase II Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Systemic Lupus Erythematosus

Обзор

The purpose of this study is to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of subcutaneous (SC) anifrolumab in pediatric participants with moderate to severe systemic lupus erythematosus (SLE) while on background standard of care (SoC) therapy.

Подробное описание

This is an open-label, multicenter study.

The study includes -

* Screening Period of up to 35 days * Period A (12-week, open-label treatment period) * Period B (a possible 12-week dosing regimen adjustment period, if required) * Treatment Extension Period (up-to-40-week, optional) * Period C (a 12-week safety follow-up period)

The study intervention (anifrolumab) will be administered subcutaneously using an accessorized pre-filled syringe (APFS) in 2 cohorts.

Вмешательства

• Комбинированный продукт Anifrolumab + APFS
  Anifrolumab will be administered as a SC injection using an APFS.

Первичные конечные точки

• Maximum observed serum (peak) concentration (Cmax) [Срок оценки: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Area under the serum concentration-time curve (AUC) [Срок оценки: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Time to maximum plasma concentration (tmax) [Срок оценки: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Apparent total body clearance of drug from plasma (CL/F) [Срок оценки: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Trough drug concentration at steady state (Ctrough,ss) [Срок оценки: At Week 12]

Вторичные конечные точки (6)

• Suppression of type I IFN 21-gene signature [Срок оценки: At Week 12 and 52]
• Change from baseline in anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies [Срок оценки: At Week 12 and 52]
• Change from baseline in complement component 3 (C3) levels [Срок оценки: At Week 12 and 52]
• Change from baseline in complement component 4 (C4) levels [Срок оценки: At Week 12 and 52]
• Change from baseline in total hemolytic complement (CH50) levels [Срок оценки: At Week 12 and 52]
• Number and percentage of participants who develop anti drug antibody (ADA) against anifrolumab [Срок оценки: From Day 1 to Week 52]

Критерии участия

Критерии включения

• Diagnosis of SLE.
• Must be receiving at least one of the following SoC regimens for ≥ 4 weeks: oral glucocorticoids (≤1.0 mg/kg/day or ≤ 40 mg/day prednisone equivalent), antimalarials (hydroxychloroquine, chloroquine, or quinacrine), or a single permitted immunosuppressant (azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, mizoribine, or tacrolimus) within specified dose limits.
• Participant must have moderate to severe active SLE disease defined as Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) ≥ 6 total points.
• Body weight ≥ 15 kg.
• Participants must agree to follow study specific contraception requirements as per local regulations.

Критерии исключения

• Known diagnosis of an IFN mediated autoinflammatory interferonopathy.
• History of, or current diagnosis of, clinically significant non-SLE related vasculitides.
• Active, severe SLE-driven renal disease with significant proteinuria.
• Active severe or unstable neuropsychiatric SLE including but not limited to aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex.
• In participants ≥ 11 years of age, a history or evidence of suicidal ideation (severity of 4 \[active: method and intent, but no plan\] or 5 \[active: method, intent, and plan\]) within the past 6 months; or any suicidal behavior within the past 12 months or recurrent suicidal behavior in the lifetime of the participant based on an assessment with the Columbia suicide severity rating scale (C-SSRS).
• History of, or current diagnosis of, catastrophic antiphospholipid syndrome (APS).
• History of recurrent or opportunistic infection requiring hospitalization and intravenous (IV) antibiotics.
• Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for human immunodeficiency virus (HIV) infection.
• Active hepatitis B and C infection.
• Any active or recent herpes zoster (HZ) infection that has not completely resolved within 12 weeks prior to study entry or that emerges between screening and Day 1.
• Any history of severe or recurrent HZ, including non-cutaneous HZ, herpes encephalitis, ophthalmic herpes, or 2 or more prior HZ episodes.
• Any cytomegalovirus (CMV) or Epstein Barr virus (EBV) infection that has not completely resolved.
• History of cancer.
• Prior receipt of anifrolumab.
• Prior treatment with directly acting cytotoxic B-cell depleting therapeutics.
• A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy, human proteins, or monoclonal antibodies (mAbs).

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07630714 · D3465C00008 · 2025-524578-41-00 · EMA/PE/0000246211

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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