Clinical Trial: Re-administration of Intramuscular AAV9 in Patients With Late-Onset Pompe Disease

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Evaluation of Re-administration of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase (rAAV9-DES-hGAA) in Patients With Late-Onset Pompe Disease (LOPD)

Brief Summary: A recombinant AAV vector has been generated to carry the codon-optimized acid alpha-glucosidase (coGAA) gene expressed from a human desmin enhancer/promoter (DES). The proposed clinical trial is a within-participant, double-blind, randomized, phase I controlled study evaluating the toxicology, biodistribution and potential activity of re-administration of rAAV9-DES-hGAA injected intramuscularly into the TA. Nine participants (18 years old or older) Late-Onset Pompe Disease (LOPD) will be included. The goal of the immune modulation strategy is to ablate B-cells (Rituximab and Sirolimus) prior to the initial exposure to the study agent in one leg and the subsequent exposure of the same vector to the contralateral leg after four months. At each study agent dosing, the contralateral leg will receive excipient. Patients will act as their own controls. Repeated measures, at baseline and during the following 3 months after each injection, will assess the safety, biochemical and functional impact of the vector.

Detailed Summary:

Enrolling in this study will entail participating in 8 months of study-related visits. Patients will be asked to come to the Clinical and Translational Research Building at the University of Florida for a series of onsite study visits, including a baseline visit, two injections of the gene transfer and two post-injection visits. All the visits, including the injections, will last two days and will be performed as outpatient procedures at the Clinical Research Center (CRC) and at other facilities at the University of Florida. Overnight observation will not be needed, however, patients will be asked to stay overnight in a hotel near the University of Florida. During the first 4 months after each injection, patients will be asked to perform outpatient laboratory work at a laboratory facility convenient for them.

In addition, during this study patients will be asked to take medications that will modulate the ability of their immune system to react against foreign agents including the gene transfer agent. The purpose of these medications is to improve the activity of the GAA within the body. Patients will need to take one medication (Rituximab) 15 days prior the first injection of the study agent and the day before each injection. Rituximab will be repeated at 2nd injection only if his/her body is producing antibody (B cells counts). Rituximab will be delivered by infusion that may last 2-6 hours. Patients will need to take another medication (Sirolimus) every day starting 3 days before the first injection of the study agent until one month after the second injection of the study agent.

The following discusses what will occur at each visit:

Baseline Baseline Evaluation and first Rituximab infusion - Day -15/-14

• Safety will be tested by clinical pathology tests, blood assay for vector genomes, antibodies against GAA and T-cell ELISPOT against GAA and AAV.