Donidalorsen Treatment in Children With Hereditary Angioedema

Официальное название

An Open-Label Study of Donidalorsen in Pediatric Patients Age 2 to Less Than 12 Years Old With Hereditary Angioedema

Обзор

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of donidalorsen in pediatric participants with hereditary angioedema (HAE) Type I (HAE-1) or Type II (HAE-2).

Подробное описание

This is an open-label study to evaluate the safety, efficacy, and pharmacokinetics (PK) and pharmacodynamics (PD) of donidalorsen in pediatric participants age 2 to less than 12 years old with HAE Type I (HAE-1) or Type II (HAE-2). The study consists of 3 parts: 1) a 3-month Screening Period, 2) a one-year Treatment Period, and 3) a 3-month Post-Treatment Period.

Вмешательства

• Препарат Donidalorsen
  Donidalorsen will be administered by subcutaneous (SC) injection.

Первичные конечные точки

• Number of Participants with Treatment Emergent Adverse Events (TEAEs) [Срок оценки: over the period of approximately 17 months]
• Maximum Plasma Concentration (Cmax) of Donidalorsen [Срок оценки: over the period of approximately 17 months]
• Maximum Time to Reach Cmax (Tmax) of Donidalorsen [Срок оценки: over the period of approximately 17 months]
• Trough Plasma Concentration (Ctrough) of Donidalorsen [Срок оценки: over the period of approximately 17 months]

Вторичные конечные точки (8)

• Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) [Срок оценки: over the period of 12 months]
• Percentage of Investigator-Confirmed HAE Attack-free Participants [Срок оценки: over the period of 12 months]
• Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month) [Срок оценки: over the period of 12 months]
• Number of Participants with a Clinical Response Defined as a ≥ 50 Percent (%), ≥ 70% and ≥ 90% Reduction from Baseline in Investigator-Confirmed HAE Attack Rate [Срок оценки: over the period of 12 months]
• Time-Normalized Number of Investigator-Confirmed HAE Attacks Requiring Rescue Treatment [Срок оценки: over the period of 12 months]
• Change From Baseline in Prekallikrein (PKK) Levels in Plasma [Срок оценки: over the period of 12 months]
• Percent Change From Baseline in PKK Levels in Plasma [Срок оценки: over the period of 12 months]
• Changes in Pediatrics Quality of Life (PedsQL) Scores for Participants [Срок оценки: over the period of 12 months]

Критерии участия

Критерии включения

• Must be between the ages of 2 and less than 12 years, inclusive, at the time of informed consent and, as applicable, assent.
• Must weigh at least 9 kg at the time of informed consent and, as applicable, assent.
• Documented diagnosis of HAE-1/HAE-2 based upon both of the following:

• Documented clinical history consistent with HAE (SC or mucosal, non-pruritic swelling episodes without accompanying urticaria).
• Diagnostic testing results that confirm HAE-1/HAE-2: C1-inhibitor (C1-INH) functional level <50% normal level AND complement factor C4 level below the lower limit of normal (LLN); OR a known pathogenic mutation in the SERPING1 gene.

Критерии исключения

• Must not have any screening laboratory abnormalities or any other clinically significant abnormalities during screening that would render a participant unsuitable for inclusion.
• Must not have been treated with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer.
• Concurrent diagnosis of any other type of recurrent angioedema, including idiopathic angioedema or HAE with normal C1-INH (HAE-nC1-INH or Type III).

Note: Other protocol-specified inclusion/exclusion criteria may 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

США · 7 центров

• Ionis Investigative Site — Santa Monica
• Ionis Investigative Site — Miami
• Ionis Investigative Site — Baton Rouge
• Ionis Investigative Site — St Louis
• Ionis Investigative Site — Cincinnati
• Ionis Investigative Site — Cleveland
• Ionis Investigative Site — Hershey

Италия · 4 центра

• Ionis Investigative Site — Milan
• Ionis Investigative Site — Padova
• Ionis Investigative Site — Roma
• Ionis Investigative Site — San Donato Milanese

Польша · 1 центр

• Ionis Investigative Site — Warsaw

Испания · 1 центр

• Ionis Investigative Site — Barcelona

Идентификаторы

NCT: NCT07298447 · ISIS 721744-CS8 · U1111-1326-8613 · 2025-523499-22-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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