A Gene Therapy Study of RP-A501 in Male Patients With Danon Disease

Официальное название

Gene Therapy for Danon Disease: A Phase 2 Study Evaluating the Efficacy and Safety of Intravenously Administered Adeno-Associated Virus Serotype 9 (rAAV9) Vector Containing the Human LAMP2 Isoform B Transgene (RP-A501; AAV9.LAMP2B) in Male Patients With Danon Disease

Обзор

This is a single arm Phase 2 trial to evaluate the efficacy and safety of RP-A501, a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene, in male patients with Danon Disease.

Подробное описание

The study is a single arm Phase 2 clinical trial to characterize the safety and efficacy of RP-A501, a recombinant adeno-associated serotype 9 (rAAV9 capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene) in male patients with Danon Disease.

Male subjects ≥8 years of age will receive a single intravenous infusion of RP-A501.

Вмешательства

• Генная терапия RP-A501
  RP-A501 is a gene therapy product consisting of a rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single IV infusion.

Первичные конечные точки

• Evaluation of efficacy via primary endpoint comprised of LAMP2 myocardial tissue expression and left ventricular mass index [Срок оценки: 12 Months post-infusion]

Вторичные конечные точки (6)

• Evaluation of efficacy via components of the primary endpoint - LAMP2 [Срок оценки: 12 months post infusion]
• Evaluation of efficacy via components of the primary endpoint - Left Ventricular Mass Index (LVMI) [Срок оценки: 12 months post infusion]
• Evaluation of efficacy via biomarker evidence of myocardial injury - High Sensitivity Troponin I (hsTnI) [Срок оценки: 12 months post infusion]
• Evaluation of efficacy via biomarker evidence of myocardial injury - N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) [Срок оценки: 12 months post infusion]
• Evaluation of efficacy via assessment of event-free survival [Срок оценки: 60 months post infusion]
• Evaluation of safety [Срок оценки: 60 months post infusion]

Критерии участия

Критерии включения

• Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.
• Male.
• Age ≥8 years.
• Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following:

• Abnormal thickening of Left ventricular wall,
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• New York Heart Association (NYHA) Class II to III.
• High sensitivity Troponin I (hsTnI) ≥20% above the upper limit of normal (ULN)
• Ability to comply with study procedures including investigational therapy and follow-up evaluations.

Критерии исключения

• Anti-AAV9 neutralizing antibody titer >1:40.
• Severe heart failure or requirement for advanced therapies.
• History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina.
• Prior cardiac or other organ (lung, liver, other) transplantation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• University of California, San Diego — La Jolla
• Boston Children's Hospital — Boston
• Children's Hospital of Philadelphia — Philadelphia

Германия · 1 центр

• German Heart Center Munich — Munich

Италия · 1 центр

• Meyer Childrens Hospital — Florence

Великобритания · 1 центр

• Great Ormund Street Hospital & UCL Institute of Cardiovascular Science — London

Идентификаторы

NCT: NCT06092034 · RP-A501-0123 · LAMPLIGHT-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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