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RecruitingNCT06996756Updated Oct 16, 2026

Gene Therapy for Alpha 1- Antitrypsin Deficiency

A Phase 1 interventional study of AAV8hAAT(AVL) in Alpha 1-Antitrypsin Deficiency, sponsored by Weill Medical College of Cornell University. Recruiting at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-10-16.

Sponsored by Weill Medical College of Cornell University · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Started Feb 2025; still recruiting 1 year 8 months later.
Updated Oct 16, 2026Study contact changedEligibility revisedGo to Updates ↓
Phase
Phase 1
Study type
Interventional
Enrollment
16
Allocation
Non-randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Alpha 1-Antitrypsin Deficiency

Keywords

  • AAT
  • Emphysema
  • Gene therapy
  • DLCO
  • Augmentation therapy
03

In context

alpha 1-Antitrypsin Deficiency

142 studies on the registry are indexed under alpha 1-Antitrypsin Deficiency; 32 are open to participants now.

This study's planned enrollment of 16 is below the median of 32 across 86 interventional studies indexed under alpha 1-Antitrypsin Deficiency.

Browse alpha 1-Antitrypsin Deficiency studies →

Lead sponsor

Weill Medical College of Cornell University is the lead sponsor of 892 studies on the registry; 165 are open to participants now.

Of its 123 completed or terminated interventional studies of FDA-regulated products, 94 (76%) have results posted.

Browse Weill Medical College of Cornell University studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

The criteria were revised on the registry on Sep 25, 2026. See what changed

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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:

      1. Mild lung dysfunction: /FVC \< 0.70 and FEV1 ≥ 80% predicted
      2. Moderate lung dysfunction: FEV1/FVC \< 0.70 and FEV1 40 - \< 80% predicted and DLCO \<80% predicted.
  • Troponin T within normal limits
  • Normal liver ultrasound and serum alpha fetoprotein
  • Normal kidney function
  • No to receiving

Exclusion criteria

Exclusion Criteria:

  • Individuals receiving chronic (used daily for greater than 30 days) systemic or other 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
  • 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 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 or anaphylaxis associated with the administration of any AAT product
Terms in these criteria, in plain language(7)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

FEV1

From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
16 participants (estimated)

Study arms

  • Experimental
    AAV8hAAT(AVL) - 5x10¹¹ gc/kg

    Lowest dose of vector genome copies per kilogram

    Biological: AAV8hAAT(AVL)

  • Experimental
    AAV8hAAT(AVL) - 2x10¹² gc/kg

    Biological: AAV8hAAT(AVL)

  • Experimental
    AAV8hAAT(AVL) - 5x10¹² gc/kg

    Biological: AAV8hAAT(AVL)

  • Experimental
    AAV8hAAT(AVL) - 2x10¹³ gc/kg

    Highest dose of vector genome copies per kilogram

    Biological: AAV8hAAT(AVL)

Interventions

  • BiologicalAAV8hAAT(AVL)

    AAV8hAAT(AVL) gene transfer vector

06

What researchers measure

Primary outcomes

  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.

    Time frame: 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.

    Time frame: 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)

    Time frame: Approximately 2 years

Secondary outcomes

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

    Serum levels of AAT will be measured in the blood

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 5 years

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: At the time of publication, and after final analyses have been completed.

Access criteria: Access to the data may require Material Transfer Agreements, Non-Disclosure Agreements, or other limitations on licensing access and will be managed by the PI

No publications or documents are linked to this record.

09

Timeline

2 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Feb 2025 (actual). Primary completion is estimated for Apr 2028, 38 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
May 21, 2025
First posted
May 30, 2025
StartActual
Feb 26, 2025
Primary completionEst.
Apr 30, 2028
CompletionEst.
Aug 1, 2032
Last update
Oct 16, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Eligibility
2 inclusion criteria edited, 3 added; 1 exclusion criterion edited, 1 removed
What changed in the criteria
Inclusion criteria
  • AddedEvidence of mild to moderate disease by the following lung function parameters on PFT and/or chest high resolution computational tomography (HRCT)
  • EditedEmphysema as assessed by chest high resolution computational tomography (HRCT)HRCT and/or
  • EditedLung function parameters consistent with mild to moderate loss of lung function and the presence of emphysema., in either category 1 or category 2 below:
  • AddedMild lung dysfunction: FEV1/FVC < 0.70 and FEV1 ≥ 80% predicted
  • AddedModerate lung dysfunction: FEV1/FVC < 0.70 and FEV1 40 - < 80% predicted and DLCO <80% predicted.
Exclusion criteria
  • EditedIndividuals 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)
  • RemovedAny history of allergies to drugs used for bronchoscopy, including xylocaine, lidocaine, versed, valium, atropine, pilocarpine, isoproterenol, terbutaline, aminophylline, or any local anesthetic
Sep 25, 2026
Contact
Study contact changed: n•••@med.cornell.edu · •••5527→m•••@med.cornell.edu · •••2672. See the current contact
Oct 16, 2026
Site contacts
Changed at 1 site. See the sites
Show the site
  • WCMC Department of Genetic Medicine · New York, United StatesContact n•••@med.cornell.edu · •••5527→m•••@med.cornell.edu · •••4508
Oct 16, 2026
Show all 2 updates
  1. Oct 16, 2026
    Contact Study contact changed: n•••@med.cornell.edu · •••5527→m•••@med.cornell.edu · •••2672. See the current contact
    Site contacts Changed at 1 site. See the sites
    Show the site
    • WCMC Department of Genetic Medicine · New York, United StatesContact n•••@med.cornell.edu · •••5527→m•••@med.cornell.edu · •••4508
    + 1 other change: verification date
  2. Sep 25, 2026
    Eligibility 2 inclusion criteria edited, 3 added; 1 exclusion criterion edited, 1 removed
    What changed in the criteria
    Inclusion criteria
    • AddedEvidence of mild to moderate disease by the following lung function parameters on PFT and/or chest high resolution computational tomography (HRCT)
    • EditedEmphysema as assessed by chest high resolution computational tomography (HRCT)HRCT and/or
    • EditedLung function parameters consistent with mild to moderate loss of lung function and the presence of emphysema., in either category 1 or category 2 below:
    • AddedMild lung dysfunction: FEV1/FVC < 0.70 and FEV1 ≥ 80% predicted
    • AddedModerate lung dysfunction: FEV1/FVC < 0.70 and FEV1 40 - < 80% predicted and DLCO <80% predicted.
    Exclusion criteria
    • EditedIndividuals 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)
    • RemovedAny history of allergies to drugs used for bronchoscopy, including xylocaine, lidocaine, versed, valium, atropine, pilocarpine, isoproterenol, terbutaline, aminophylline, or any local anesthetic
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06996756
Lead sponsor
Weill Medical College of Cornell University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Sponsor
First posted
May 30, 2025
Start date
Feb 26, 2025
Primary completion
Apr 30, 2028 (estimated)
Completion
Aug 1, 2032 (estimated)
Last update
Oct 16, 2026

Study contacts

Madeline Galbraith
Contact
meg4013@med.cornell.edu
646-962-2672
Sandra Hyde
Contact
sah2003@med.cornell.edu
646-962-2672
Ronald G Crystal, MD
principal investigator · Weill Medical College of Cornell University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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