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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
AAV8hAAT(AVL) gene transfer vector
WCMC Department of Genetic Medicine
New York, New York, United States
RECRUITINGSafety of AAV8hAAT(AVL), as measured by number of subjects with at least 1 serious adverse event.
Serious adverse events will only be included if assessed as related to the gene therapy.
Time frame: Approximately 1 year
Toxicity of AAV8AAT(AVL), as measure by number of subjects with any dose limiting toxicity
If none of the first 4 dosed participants experiences a DLT by the end of Day 28 after treatment (Day 1), the dose of AAV8hAAT(AVL) will be escalated, and the next cohort of participants will start treatment at the next-higher dose level.
Time frame: Approximately 2 years
Establishing a maximum tolerable dose of AAV8hAAT(AVL)
If none of the first 4 participants treated at the highest dose level experiences a DLT by the end of Day 28 after treatment, this dose will be determined to be the maximum administered dose (MAD)
Time frame: Approximately 2 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 4 weeks
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 3 months
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 6 months
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
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Serum levels of AAT will be measured in the blood
Time frame: 12 months
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 2 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 3 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 4 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum
Serum levels of AAT will be measured in the blood
Time frame: 5 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid
Levels of AAT in the lung will be measured by bronchoscopy (if performed)
Time frame: 12 months
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid
Levels of AAT in the lung will be measured by bronchoscopy (if performed)
Time frame: 2 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid
Levels of AAT in the lung will be measured by bronchoscopy (if performed)
Time frame: 3 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid
Levels of AAT in the lung will be measured by bronchoscopy (if performed)
Time frame: 4 years
Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid
Levels of AAT in the lung will be measured by bronchoscopy (if performed)
Time frame: 5 years