Gene Therapy for Alpha 1-Antitrypsin Deficiency

This study is testing a gene therapy called AAV8hAAT(AVL) for people with Alpha 1-Antitrypsin (AAT) deficiency. AAT deficiency is a genetic condition that can cause lung damage like emphysema. The goal of this study is to see how safe AAV8hAAT(AVL) is and if it can help protect the lungs. This gene therapy works by giving your body instructions to make a special, protective form of the AAT protein. You might be able to join if you are between 18 and 70 years old, have a specific AAT genetic type (ZZ or Z null heterozygotes), and have mild to moderate emphysema. The study plans to enroll 16 participants, but its current status is unclear.

Study design: This is an interventional study, meaning participants will receive a treatment. It aims to enroll 16 participants.
What's involved: Not specified in the trial record.
Compensation: Not stated in the trial record.
Follow-up: Participants will be followed for safety for approximately 1 year, and for toxicity and maximum tolerable dose for approximately 2 years.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

Gene Therapy for Alpha 1- Antitrypsin Deficiency

Recruiting

PHASE1Ages 18–70InterventionalTreatment

Weill Medical College of Cornell University

~16 participants

Updated 2026-03-13 on ClinicalTrials.gov

What's tested:AAV8hAAT(AVL)

At a glance

Recruiting sites

1 of 1 listed site is recruiting right now

RecruitingSuspended, closed, or not yet open

What they're measuring

Safety of AAV8hAAT(AVL), as measured by number of subjects with at least 1 serious adverse event.

Measured over Approximately 1 year

+2 more outcomes measured

Conditions

Alpha 1-Antitrypsin Deficiency

Where it's being run

1 sites across 1 states

New York1

Study leadership

Ronald G Crystal, MD · PRINCIPAL_INVESTIGATOR · Weill Medical College of Cornell University

Who to contact

Niamh Savage

[email protected]

646-962-5527

Email the study team

Opens a ready-to-send draft in your own email app — review before sending.

Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

Check eligibility for this trial ~2 min · HIPAA-protected · delete anytime

Eligibility criteria

Inclusion

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

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

What this trial measures

Safety of AAV8hAAT(AVL), as measured by number of subjects with at least 1 serious adverse event.Approximately 1 year
Serious adverse events will only be included if assessed as related to the gene therapy.
Toxicity of AAV8AAT(AVL), as measure by number of subjects with any dose limiting toxicityApproximately 2 years
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.
Establishing a maximum tolerable dose of AAV8hAAT(AVL)Approximately 2 years
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)

Trialytics