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

• Status: Active, not recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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 to 50-years old) who reside within the United States with 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Florida
• Treatments: Acetaminophen; Diphenhydramine; Everolimus; Lidocaine; Promethazine; Rituximab; Sirolimus

Criteria

Inclusion Criteria:

• Male or female subjects 18 to 50-years old

• Have a diagnosis of Pompe disease, as defined by protein assay AND/OR DNA sequence of the acid alpha-glucosidase gene, AND clinical symptoms of the disease

• Have residual ability to complete the 10 meter walk test

• Willing to discontinue aspirin, aspirin-containing products and other drugs that may alter platelet function, 7 days prior to dosing, resuming 24 hours after the dose has been administered

• Consistently taking enzyme replacement therapy (ERT) or remain off ERT from baseline until Day 520

• United States residents only.

Exclusion Criteria:

• Be pregnant or nursing, and if the subject is of child bearing potential they should use contraception until the end of the study

• Have required oral or systemic corticosteroids within the last 15 days prior to baseline screening

• Have a platelet count less than 75,000/mm^3

• Have an INR greater than 1.3

• Have seronegative to AAV9 capsid protein (neutralizing Ab titers <1:5 and total binding Ab titer <50 U/ml)

• Have transaminases and alkaline phosphatase more than ten times the upper limit of normal at screening or Day-1

• Have bilirubin and gamma-glutamyl transpeptidase greater than 2 times the upper limit of normal at screening or Day -1

• Have any chronic liver disease (aside from hepatic dysfunction related to Pompe disease) such as hepatitis B and C and cirrhosis

• Be currently, or within the past 30 days, participating in any other research protocol involving investigational agents or therapies

• Have history of platelet dysfunction, evidence of abnormal platelet function at screening, or history of recent use of drugs that may alter platelet function, which the subject is unable/unwilling to discontinue for study agent administration

• Have received gene transfer agents within the past 6 months

• Have any medical condition or circumstance for which an MRI evaluation is contraindicated

• Have any other concurrent condition that, in the opinion of the investigator, would make the subject unsuitable for the study

• Inconsistent with use of ERT.