Gene Therapy for Alpha-1 Antitrypsin Deficiency

NCT ID: NCT06996756

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-26
• Study Completion Date: 2032-08-01

Brief Summary

This is a study of gene therapy to treat alpha-1 antitrypsin 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 (AAT) deficient individuals.

Conditions

Alpha 1-Antitrypsin Deficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AAV8hAAT(AVL) - 5x10¹¹ gc/kg

Lowest dose of vector genome copies per kilogram

Group Type: EXPERIMENTAL

AAV8hAAT(AVL)

Intervention Type: BIOLOGICAL

AAV8hAAT(AVL) gene transfer vector

AAV8hAAT(AVL) - 2x10¹² gc/kg

Group Type: EXPERIMENTAL

AAV8hAAT(AVL)

Intervention Type: BIOLOGICAL

AAV8hAAT(AVL) gene transfer vector

AAV8hAAT(AVL) - 5x10¹² gc/kg

Group Type: EXPERIMENTAL

AAV8hAAT(AVL)

Intervention Type: BIOLOGICAL

AAV8hAAT(AVL) gene transfer vector

AAV8hAAT(AVL) - 2x10¹³ gc/kg

Highest dose of vector genome copies per kilogram

Group Type: EXPERIMENTAL

AAV8hAAT(AVL)

Intervention Type: BIOLOGICAL

AAV8hAAT(AVL) gene transfer vector

Interventions

AAV8hAAT(AVL)

AAV8hAAT(AVL) gene transfer vector

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald G Crystal, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

WCMC Department of Genetic Medicine

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Niamh Savage

Role: CONTACT

nis2049@med.cornell.edu

646-962-5527

Sandra Hyde

Role: CONTACT

sah2003@med.cornell.edu

646-962-2672

Facility Contacts

Sandra Hyde

Role: primary

sah2003@med.cornell.edu

646-962-2672

Niamh Savage

Role: backup

nis2049@med.cornell.edu

646-962-5527

Other Identifiers

1R61HL169190

Identifier Type: NIH

Identifier Source: secondary_id

View Link

24-06027591

Identifier Type: -

Identifier Source: org_study_id