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Sponsors and Collaborators: |
National Heart, Lung, and Blood Institute (NHLBI) Applied Genetic Technologies Corp Alpha-1 Foundation University of Florida National Center for Research Resources (NCRR) |
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Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
ClinicalTrials.gov Identifier: | NCT00430768 |
Individuals with a deficiency of the alpha 1-antitrypsin (AAT) protein are at risk for developing emphysema and liver damage. Researchers have developed a way to introduce normal AAT genes into muscle cells with the expectation that the AAT protein may be produced at normal levels. This study will evaluate the safety of the experimental gene transfer procedure in individuals with AAT deficiency. The study will also determine what dose may be required to achieve normal levels of AAT.
Condition | Intervention | Phase |
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Alpha 1-Antitrypsin Deficiency |
Biological: rAAV1-CB-hAAT |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Preclinical & Phase I/II Trials of AAV-AAT Vectors: Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV1-CB-hAAT) Gene Vector to AAT-Deficient Adults |
Enrollment: | 9 |
Study Start Date: | February 2006 |
Estimated Study Completion Date: | March 2013 |
Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Group 1: Experimental
6.9 x1012 vector genomes
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Biological: rAAV1-CB-hAAT
Three groups of 3 subjects in drug escalation. Group 1 receives rAAV1-CB-hAAT 6.9 x1012 vg (vector genomes), Group 2 receives rAAV1-CB-hAAT 2.1 x1013 vg, and Group 3 receives rAAV1-CB-hAAT 6.0 x1013 vg
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Group 2: Experimental
2.1 x 1013 vector genomes
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Biological: rAAV1-CB-hAAT
Three groups of 3 subjects in drug escalation. Group 1 receives rAAV1-CB-hAAT 6.9 x1012 vg (vector genomes), Group 2 receives rAAV1-CB-hAAT 2.1 x1013 vg, and Group 3 receives rAAV1-CB-hAAT 6.0 x1013 vg
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Group 3: Experimental
rAAV1-CB-hAAT 6.0 x1013 vg
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Biological: rAAV1-CB-hAAT
Three groups of 3 subjects in drug escalation. Group 1 receives rAAV1-CB-hAAT 6.9 x1012 vg (vector genomes), Group 2 receives rAAV1-CB-hAAT 2.1 x1013 vg, and Group 3 receives rAAV1-CB-hAAT 6.0 x1013 vg
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AAT deficiency is a genetic disorder in which individuals have inadequate levels of the AAT protein. AAT protects the lungs from white blood cell enzymes that can damage air sacs within the lungs, potentially leading to emphysema. Experimental gene transfer procedures, in which normal copies of genes are inserted into cells, are being developed to treat many genetic diseases, including AAT deficiency. In this study, a modified virus, adeno-associated virus (AAV), has been genetically engineered to contain a normal copy of the AAT gene. When AAV is combined with the AAT gene, the resulting agent, rAAV1-CB-hAAT, may be able to carry normal copies of the AAT gene into muscle cells with the expectation that additional AAT would be produced. The purpose of this study is to evaluate the safety of injecting rAAV1-CB-hAAT into individuals with AAT deficiency.
This 14-month study will enroll individuals with AAT deficiency. Participants currently using AAT protein replacement will discontinue its use for 19 weeks during the study. Participants will first attend a baseline study visit, which will include a medical history review; a physical examination; an electrocardiogram (ECG) to record heart activity; blood, urine, and semen collection; pulmonary function tests; and chest and arm scans. Participants will then attend a 5-day inpatient visit, during which they will receive a series of injections consisting of one of four different doses of rAAV1-CB-hAAT. Physical examinations will occur on all 5 inpatient days; pulmonary function testing, arm circumference measurements, and collection of blood, urine, and semen will occur on selected days of the inpatient stay. Follow-up study visits, with possible overnight stays, will occur on Days 14 and 90. On Days 30, 45, 60, 75, 180, 270, and 365, participants will have blood drawn at a local clinic. On these same days, study staff will contact participants by telephone to review their medical history and symptoms. Unused blood and semen samples will be frozen and stored for future research purposes. Participants will have yearly follow-up evaluations by either telephone or mail for a total of 5 years.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Florida | |
University of Florida, College of Medicine, Department of Pediatrics | |
Gainesville, Florida, United States, 32610 | |
United States, Massachusetts | |
University of Massachusetts School of Medicine | |
Worcester, Massachusetts, United States, 01655 |
Principal Investigator: | Terence R. Flotte, MD | UMass Medical School |
Principal Investigator: | Mark L Brantly, MD | University of Florida |
Responsible Party: | UFL Medicine/UMass School of Medicine Worcester ( Terence R. Flotte, MD ) |
Study ID Numbers: | 438, Grant 1 R01 HL069877-03, NIH 0404-638, GCRC # 611, UF IBC RD 2630, AGTC-AAV1-001, WIRB # 20052374 |
Study First Received: | January 31, 2007 |
Last Updated: | May 14, 2008 |
ClinicalTrials.gov Identifier: | NCT00430768 |
Health Authority: | United States: Food and Drug Administration |
Gene Transfer Techniques Gene Therapy AAV |
AAT Phase I Intramuscular transfer |
Virus Diseases Protein C Inhibitor Alpha 1-Antitrypsin |
Alpha 1-Antitrypsin Deficiency Alpha 1-antitrypsin deficiency Connective Tissue Diseases |
Serine Proteinase Inhibitors Molecular Mechanisms of Pharmacological Action Trypsin Inhibitors |
Enzyme Inhibitors Pharmacologic Actions Protease Inhibitors |