RECRUITING

Gene Therapy for Alpha-1 Antitrypsin Deficiency

Conditions

Alpha 1-Antitrypsin Deficiency AAT Emphysema Gene therapy DLCO Augmentation therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Gene Therapy for Alpha-1 Antitrypsin Deficiency

Quick Facts

Study Start:2025-02-26

Study Completion:2032-08-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06996756

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Niamh Savage

CONTACT

646-962-5527

nis2049@med.cornell.edu

Sandra Hyde

CONTACT

646-962-2672

sah2003@med.cornell.edu

Principal Investigator

Ronald G Crystal, MD

PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Study Locations (Sites)

WCMC Department of Genetic Medicine

New York, New York, 10021

United States

Collaborators and Investigators

Sponsor: Weill Medical College of Cornell University

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-26

Study Completion Date2032-08-01

Study Record Updates

Study Start Date2025-02-26

Study Completion Date2032-08-01

Terms related to this study

Keywords Provided by Researchers

AAT
Emphysema
Gene therapy
DLCO
Augmentation therapy

Additional Relevant MeSH Terms

Alpha 1-Antitrypsin Deficiency