Recruiting
Phase 1

AAV8hAAT(AVL)

Sponsor:

Weill Medical College of Cornell University

Code:

NCT06996756

Conditions

Alpha 1-Antitrypsin Deficiency

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

AAV8hAAT(AVL)

Study Details

Brief summary:

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Study ID

NCT06996756

Start date

Feb 26, 2025

Status verified date

Mar, 2026

Completion date

Aug 1, 2032

Anticipated

Primary completion date

Apr 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

16 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: AAV8hAAT(AVL) - 5x10¹¹ gc/kg

Lowest dose of vector genome copies per kilogram

experimental: AAV8hAAT(AVL) - 2x10¹² gc/kg

experimental: AAV8hAAT(AVL) - 5x10¹² gc/kg

experimental: AAV8hAAT(AVL) - 2x10¹³ gc/kg

Highest dose of vector genome copies per kilogram

Interventions

AAV8hAAT(AVL)

AAV8hAAT(AVL) gene transfer vector

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Niamh Savage

646-962-5527nis2049@med.cornell.edu

Sandra Hyde

646-962-2672sah2003@med.cornell.edu

Locations

WCMC Department of Genetic Medicine

Recruiting

New York, New York, United States, 10021

Contacts

Sandra Hyde

646-962-2672sah2003@med.cornell.edu

Niamh Savage

646-962-5527nis2049@med.cornell.edu

Principal Investigator:

Ronald Crystal, MD

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Mar 13, 2026

Last verified

Mar, 2026

Keywords

  • AAT
  • Emphysema
  • Gene therapy
  • DLCO
  • Augmentation therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2026-03-13.