Gene Therapy for Alpha-1 Antitrypsin Deficiency

Overseen By Sandra Hyde

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Corticosteroids, Immunosuppressants, Beta-blockers, others

Disqualifiers: Immunodeficiency, Cardiovascular disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 1 day

16 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Ronald G Crystal, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for individuals with Alpha-1 Antitrypsin Deficiency, a genetic condition that can cause lung and liver disease. Participants should be adults who have confirmed deficiency and are willing to undergo gene therapy. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

Troponin T within normal limits

My lung function is mildly to moderately reduced, and I have emphysema.

My kidney function is normal.

Exclusion Criteria

I am taking steroids or other drugs that affect my immune system for a condition I already had.

I am allergic to certain drugs used in lung exams.

Prior history of hypersensitivity or anaphylaxis associated with the administration of any AAT product

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single administration of AAV8hAAT(AVL) gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits over 5 years

Treatment Details

Interventions

• AAV8hAAT(AVL)

Trial Overview The study tests a single administration of AAV8hAAT(AVL), which is a gene therapy designed to deliver an oxidation-resistant form of the AAT protein directly into the bloodstream, aiming for persistent protection of the lungs.

Participant Groups

Group I: AAV8hAAT(AVL) - 5x10¹¹ gc/kg Experimental Treatment 1 Intervention

Lowest dose of vector genome copies per kilogram

Group II: AAV8hAAT(AVL) - 5x10¹² gc/kg Experimental Treatment 1 Intervention

Group III: AAV8hAAT(AVL) - 2x10¹³ gc/kg Experimental Treatment 1 Intervention

Highest dose of vector genome copies per kilogram

Group IV: AAV8hAAT(AVL) - 2x10¹² gc/kg Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+