Clinical Trial: Safety Study of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase to Treat Pompe Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I/II Trial of Diaphragm Delivery of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase (rAAV1-CMV-GAA) Gene Vector in Patients With Pompe Disease

Brief Summary: Pompe disease is an inherited condition of acid alpha-glucosidase (GAA) deficiency resulting in lysosomal accumulation of glycogen in all tissues. Glycogen accumulation leads to muscle dysfunction and profound muscle weakness. A wide spectrum of disease is characteristic and the most severe patients have cardiorespiratory failure, often fatal in the first two years of life. Researchers have developed a way to introduce the normal GAA gene into muscle cells with the expectation that the GAA protein will be produced at levels sufficient to reduce glycogen accumulation. This study will evaluate the safety of the experimental gene transfer procedure in individuals with GAA deficiency. The study will also determine what dose may be required to achieve improvement in measures of respiratory function.

Detailed Summary:

The goal of the current study is to evaluate an experimental gene transfer procedure in which normal copies of the GAA gene are inserted into cells. In this study, a modified virus, adeno-associated virus (AAV), has been engineered to carry a normal copy of the GAA gene, known as rAAV1-CMV-hGAA, which is used to place normal copies of the GAA gene into diaphragm muscle cells. The purpose of this study is to evaluate the safety of rAAV1-CMV-hGAA delivery into individuals with GAA deficiency (Pompe Disease).

Participants currently using enzyme replacement therapy will continue to receive their regular medical regimen during the 12 month duration of the study. Participants will first attend a screening study visit to confirm study eligibility. Participants will then attend a 3-5 day inpatient visit, during which they will receive a series of intradiaphragmatic injections consisting of the study agent (rAAV1-CMV-hGAA). Follow-up study visits will occur on Days 14, 90, 180, 270 and 365. Participants will have yearly follow-up evaluations by either telephone or mail for a total of 15 years, or as required by the FDA and other regulatory agencies.

Sponsor: University of Florida

Current Primary Outcome: Safety assessments of the rAAV1-CMV-GAA (study agent), changes post study agent administration. [ Time Frame: Change from baseline, in days 14, 90, 180 and 365 post study agent administration. ]

Original Primary Outcome: Assessment of the safety of intramuscular administration of a recombinant adeno-associated virus, rAAV1-CMV-GAA, vector in children with ventilator-dependent Pompe disease. [ Time Frame: Days 1, 2, 3, 14, 30, 60 90, and 180 of the trial ]

Current Secondary Outcome:

• Change in pulmonary function testing from baseline pulmonary function testing [ Time Frame: Baseline, Day 14, 90, 180, 270, and 365 post study agent administration ]
  Pulmonary Function Testing including Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP)
• Evaluation of Ventilatory performance benefit of rAAV1-CMV-GAA gene transfer and Respiratory Muscle Strength Training (RMST) compared to RMST alone. [ Time Frame: Screening, Baseline, (pre-study agent administration) and Day 14, 90, 180, 270, and 365 post study agent administration. ]
  Pulmonary Function Testing to include: MIP, Best Unassisted Tidal Volume (TV), Maximal Voluntary Ventilation (MVV), Unassisted Ventilatory Endurance.

Original Secondary Outcome: Determination of the dose of rAAV1-CMV-GAA vector required to achieve diaphragm transduction and restoration of GAA activity in the diaphragm. [ Time Frame: 14 and 90 days post injection ]

Information By: University of Florida

Dates:
Date Received: July 13, 2009
Date Started: September 2010
Date Completion:
Last Updated: December 8, 2015
Last Verified: December 2015