Gene Therapy for Alpha 1-Antitrypsin Deficiency

Clinical Trial Details

Alpha 1-antitrypsin deficiency is a genetically inherited condition that affects the lungs and/or the liver. It is passed on from parents to their children through genes. It is a progressive condition, which means it may worsen over time. AAT normally protects the lung from damage. In this condition, the AAT protein is abnormal and cannot be released from the liver to protect the lungs. This can result in chronic obstructive pulmonary disease (COPD). It can lead to serious lung and/or liver disease.

For the current therapy, symptoms can be treated with standard medical therapy (such as bronchodilators), augmentation therapy (giving patients the AAT protein by intravenous infusion, usually every week or every month) and/or behavioral measures (such as smoking cessation).
   
This study aims to treat AAT deficiency with a single administration of AAV8hAAT(AVL), a gene therapy that codes for the AAT protein, which if safe and efficacious, and will protect the lung on a persistent basis. The term, ‘gene therapy’ is used to refer to the process of transferring a missing gene through a vector to reduce symptoms of disease.
   
In this study, we hope to learn the safety/toxicity and initial evidence of efficacy of intravenous delivery of gene therapy to AAT deficient individuals.

Key Eligibility: 
  1. Males and females age between 18 and 70 years old
  2. AAT genotype ZZ, or Z null heterozygotes (prior genomic analysis will be accepted), and if on augmentation therapy, pre-therapy AAT serum levels <11 μM
  3. Emphysema as assessed by chest high resolution computational tomography (HRCT)
  4. Evidence of mild to moderate disease by the following lung function parameters on PFT and/or chest high resolution computational tomography (HRCT)
        • Emphysema as assessed by HRCT and/or
        • Lung function parameters consistent with mild to moderate loss of lung function, in either category 1 or category 2 below:
        1. Mild lung dysfunction: FEV1/FVC &lt; 0.70 and FEV1 ≥ 80% predicted
        2. Moderate lung dysfunction: FEV1/FVC &lt; 0.70 and FEV1 40 - &lt; 80% predicted and DLCO &lt; 80% predicted

Detailed eligibility will be discussed when reaching out to the study team. 

Study contact by location

Upper East Side - Manhattan

Contact(s)

Madeline Galbraith
(646) 962-4508

Primary Investigator(s)

Protocol ID(s)

Weill Cornell Medicine IRB #:

2406027591

ClinicalTrials.gov:

NCT06996756

Status

Open to Enrollment

Age Group

Adult

Sponsor