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NCT Number: NCT06996756

Gene Therapy for Alpha 1- Antitrypsin Deficiency

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.

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Key information

Conditions

Alpha 1-Antitrypsin Deficiency Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Emphysema Genetic Diseases, Inborn Liver Diseases Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Subcutaneous Emphysema

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AAV8hAAT(AVL)

Biological

AAV8hAAT(AVL) gene transfer vector

Primary outcomes

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

    Time frame: Approximately 1 year

    Serious adverse events will only be included if assessed as related to the gene therapy.

  2. Toxicity of AAV8AAT(AVL), as measure by number of subjects with any dose limiting toxicity

    Time frame: Approximately 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.

  3. Establishing a maximum tolerable dose of AAV8hAAT(AVL)

    Time frame: 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)

Secondary outcomes

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

    Time frame: 4 weeks

    Serum levels of AAT will be measured in the blood

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

    Time frame: 3 months

    Serum levels of AAT will be measured in the blood

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

    Time frame: 6 months

    Serum levels of AAT will be measured in the blood

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

    Time frame: 12 months

    Serum levels of AAT will be measured in the blood

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

    Time frame: 2 years

    Serum levels of AAT will be measured in the blood

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

    Time frame: 3 years

    Serum levels of AAT will be measured in the blood

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

    Time frame: 4 years

    Serum levels of AAT will be measured in the blood

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

    Time frame: 5 years

    Serum levels of AAT will be measured in the blood

  9. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid

    Time frame: 12 months

    Levels of AAT in the lung will be measured by bronchoscopy (if performed)

  10. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid

    Time frame: 2 years

    Levels of AAT in the lung will be measured by bronchoscopy (if performed)

  11. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid

    Time frame: 3 years

    Levels of AAT in the lung will be measured by bronchoscopy (if performed)

  12. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid

    Time frame: 4 years

    Levels of AAT in the lung will be measured by bronchoscopy (if performed)

  13. Efficacy of AAV8hAAT(AVL) as measured by the levels of AAT in lung epithelial lining fluid

    Time frame: 5 years

    Levels of AAT in the lung will be measured by bronchoscopy (if performed)

Study contacts

Contact information is provided by the study sponsor or research team.

Niamh Savage

CONTACT

[email protected]

646-962-5527

Sandra Hyde

CONTACT

[email protected]

646-962-2672

Sponsors and collaborators

Lead sponsor

Weill Medical College of Cornell University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Important dates

Study start
2025
Primary completion
2028
Study completion
2032
First posted
May 30, 2025
Registry last updated
Mar 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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