Safety Study of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase to Treat Pompe Disease
Condition: Pompe Disease
MeSH terms: Glycogen Storage Disease Type II
Study type: Interventional
Phase: Phase 1/Phase 2

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 description: 
      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.
    

Intervention name(s): rAAV1-CMV-GAA (study agent) Administration; RMST
Intervention type(s): Drug; Other
Intervention description(s): rAAV1-CMV-GAA via intramuscular injection into the diaphragm. Dose selection for cohort 1: 1.0 x 10e12 vector genomes Cohort 1 will have a total of 3 participants enrolled. Dose selection for cohort 2 and 3: 5.0 x 10e12 vector genomes rAAV1-CMV-GAA. Cohort 2 = 6 subjects.; After enrollment and screening visit, the subject will be given a RMST prescription and will complete RMST for a minimum of 4 weeks prior to study agent administration. RMST prescription will be adjusted as needed at Day 14, 90, 180, and 270.
Other intervention name(s): Gene transfer; study agent (rAAV1-CMV-GAA); Respiratory Muscle Strength Training
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Gene Therapy; Pompe Disease; Glycogen Storage Disease