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Alpha 1-Antitrypsin DeficiencyPhase 1NCT06996756

Gene Therapy for Alpha 1- Antitrypsin Deficiency

A Phase 1 study testing AAV8hAAT(AVL) in people with Alpha 1-Antitrypsin Deficiency, run by Weill Medical College of Cornell University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Alpha 1-Antitrypsin Deficiency
What is being tested?
AAV8hAAT(AVL)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
26 Feb 2025to 1 Aug 2032
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • AAT genotype ZZ, or Z null heterozygotes, and if on augmentation therapy, pre-therapy AAT serum levels <11 μM
  • 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:
  • Mild lung dysfunction: FEV1/FVC < 0.70 and FEV1 ≥ 80% predicted
  • Moderate lung dysfunction: FEV1/FVC < 0.70 and FEV1 40 - < 80% predicted and DLCO <80% predicted.
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  • Troponin T within normal limits
  • Normal liver ultrasound and serum alpha fetoprotein
  • Normal kidney function
  • No contraindications to receiving corticosteroid immunosuppression

Who cannot join

  • Individuals receiving chronic (used daily for greater than 30 days) systemic corticosteroids or other immunosuppressive medications for pre-existing conditions (inhaled corticosteroids for pulmonary associated issues are permitted)
  • 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)
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  • Abnormal ECG at screening with findings consistent with cardiac disease
  • Females who are currently pregnant or lactating
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Madeline Galbraith contact

646-962-2672

meg4013@med.cornell.edu

Sandra Hyde contact

646-962-2672

sah2003@med.cornell.edu

United States1 site, 1 recruiting

  • WCMC Department of Genetic Medicine

    New York, New York, 10021

    Sandra Hyde, 646-962-2672, sah2003@med.cornell.edu

    Maddie Galbraith, 646-962-4508, meg4013@med.cornell.edu

    Recruiting

Other trials in United States

About this study

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.

Being tested
AAV8hAAT(AVL)
Keywords
AAT, Emphysema, Gene therapy, DLCO, Augmentation therapy
Medical subject headings
alpha 1-Antitrypsin Deficiency, Emphysema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AAV8hAAT(AVL)Biological

    AAV8hAAT(AVL) gene transfer vector

Study groups in NCT06996756
Study groupRoleWhat they receive
AAV8hAAT(AVL) - 5x10¹¹ gc/kgExperimentalLowest dose of vector genome copies per kilogram
Receives: Biological: AAV8hAAT(AVL)
AAV8hAAT(AVL) - 2x10¹² gc/kgExperimentalNot described
Receives: Biological: AAV8hAAT(AVL)
AAV8hAAT(AVL) - 5x10¹² gc/kgExperimentalNot described
Receives: Biological: AAV8hAAT(AVL)
AAV8hAAT(AVL) - 2x10¹³ gc/kgExperimentalHighest dose of vector genome copies per kilogram
Receives: Biological: AAV8hAAT(AVL)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety 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.

    Measured: Approximately 1 year

  2. 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.

    Measured: Approximately 2 years

  3. 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)

    Measured: Approximately 2 years

Secondary outcomes (13)

  1. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 4 weeks

  2. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 3 months

  3. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 6 months

  4. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 12 months

  5. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 2 years

  6. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 3 years

  7. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 4 years

  8. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in serum

    Serum levels of AAT will be measured in the blood

    Measured: 5 years

  9. 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)

    Measured: 12 months

  10. 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)

    Measured: 2 years

  11. 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)

    Measured: 3 years

  12. 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)

    Measured: 4 years

  13. 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)

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2025
  2. Study start26 Feb 2025
  3. Primary completion30 Apr 2028 (estimated)
  4. Study completion1 Aug 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06996756
Sponsor's protocol ID
24-06027591
Other IDs
1R61HL169190
Status last verified
Oct 2026
First submitted
21 May 2025
Last updated
16 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: As the proposed experiments become published in scientific journals, the cleaned, item-level spreadsheet data for all variables will also be shared openly, along with example quantifications and transformations from initial raw data. Final files used to generate specific analyses to answer the Specific Aims and related results will also be shared. The rationale for sharing only cleaned data is to foster ease of data reuse. If any data collection arising from the proposed studies are not shared by publication within one year after the proposed award period ends, the unpublished data will be similarly shared in public domains for ease of access.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AAV8hAAT(AVL) in people with Alpha 1-Antitrypsin Deficiency, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Madeline Galbraith (646-962-2672, meg4013@med.cornell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06996756.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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