Gene Therapy for Alpha 1- Antitrypsin Deficiency

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.

Eligibility

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

Conditions2

Interventions1

Locations1 site

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