Gene Therapy for Alpha 1- Antitrypsin Deficiency

Обзор

This is a study of gene therapy to treat alpha 1-antitrypsin (AAT) deficiency. This study aims to treat AAT deficiency with a single administration of AAV8hAAT(AVL), a gene therapy that codes for an oxidation resistant form of the AAT protein, which if safe and if efficacious, will protect the lung on a persistent basis. We hope to learn the safety/toxicity and initial evidence of efficacy of intravenous delivery of this gene therapy to alpha 1-antitrypsin deficient individuals.

Вмешательства

• Биопрепарат AAV8hAAT(AVL)
  AAV8hAAT(AVL) gene transfer vector

Первичные конечные точки

• Safety of AAV8hAAT(AVL), as measured by number of subjects with at least 1 serious adverse event. [Срок оценки: Approximately 1 year]
• Toxicity of AAV8AAT(AVL), as measure by number of subjects with any dose limiting toxicity [Срок оценки: Approximately 2 years]
• Establishing a maximum tolerable dose of AAV8hAAT(AVL) [Срок оценки: Approximately 2 years]

Вторичные конечные точки (12)

• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 4 weeks]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 3 months]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 6 months]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 12 months]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 2 years]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 3 years]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 4 years]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum [Срок оценки: 5 years]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid [Срок оценки: 12 months]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid [Срок оценки: 2 years]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid [Срок оценки: 3 years]
• Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid [Срок оценки: 4 years]

Критерии участия

Критерии включения

• AAT genotype ZZ, or Z null heterozygotes, and if on augmentation therapy, pre-therapy AAT serum levels <11 μM
• Emphysema as assessed by chest high resolution computational tomography (HRCT)
• Lung function parameters consistent with mild to moderate loss of lung function and the presence of emphysema.
• Troponin T within normal limits
• Normal liver ultrasound and serum alpha fetoprotein
• Normal kidney function
• No contraindications to receiving corticosteroid immunosuppression

Критерии исключения

• Individuals receiving systemic corticosteroids or other immunosuppressive medications for pre-existing conditions.
• Inability to tolerate immunosuppression with corticosteroids (e.g., uncontrolled diabetes)
• Individuals with an immunodeficiency disease, or evidence of active infection of any type, including human immunodeficiency virus
• Evidence of major central nervous system, major psychiatric, musculoskeletal or immune disorder
• Prior history of myocardial infarction or cancer within the past 5 years (other than basal cell carcinoma of the skin)
• Decompensated heart failure (NY4A class III-IV at time of baseline clinical assessment)
• Abnormal ECG at screening with findings consistent with cardiac disease
• Females who are currently pregnant or lactating
• Any history of allergies to drugs used for bronchoscopy, including xylocaine, lidocaine, versed, valium, atropine, pilocarpine, isoproterenol, terbutaline, aminophylline, or any local anesthetic
• Individuals receiving experimental medications or participating in another experimental protocol for at least 3 months prior to entry to the study
• Use of oxygen supplementation
• Risk for thromboembolic disease
• History of significant cardiovascular disease, hypertension, prior myocardial infarction and/or cerebrovascular event
• Individuals who are currently on beta-blockers, or other cardiac therapy related drugs
• Prior history of hypersensitivity or anaphylaxis associated with the administration of any AAT product

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

США · 1 центр

• WCMC Department of Genetic Medicine — New York

Идентификаторы

NCT: NCT06996756 · 24-06027591 · 1R61HL169190

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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