Health TrialsbyHealthPanel

Gene Therapy for Alpha 1- Antitrypsin Deficiency

ConditionAlpha 1-Antitrypsin Deficiency
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-70
SponsorWeill Medical College of Cornell University

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Mild lung dysfunction: FEV1/FVC < 0.70 and FEV1 ≥ 80% predicted

Disqualifiers

Individuals 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)

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • AAV8hAAT(AVL)

    Biological/Vaccine

    AAV8hAAT(AVL) gene transfer vector

Treatment groups

16 Participants
are divided into 4 treatment groups
Group A: AAV8hAAT(AVL) - 5x10¹¹ gc/kgExperimental treatment 1 intervention
Group B: AAV8hAAT(AVL) - 2x10¹² gc/kgExperimental treatment 1 intervention
Group C: AAV8hAAT(AVL) - 5x10¹² gc/kgExperimental treatment 1 intervention
Group D: AAV8hAAT(AVL) - 2x10¹³ gc/kgExperimental treatment 1 intervention

Trial outcomes

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Weill Medical College of Cornell University

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Source ClinicalTrials.gov
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