Pompe Disease Clinical Trial
— AAV9-GAA_IMOfficial title:
Evaluation of Re-administration of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase (rAAV9-DES-hGAA) in Patients With Late-Onset Pompe Disease (LOPD)
Verified date | March 2022 |
Source | University of Florida |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 2 |
Est. completion date | August 26, 2021 |
Est. primary completion date | August 26, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 50 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | Clinical and Translational Research Building (CTRB), University of Florida | Gainesville | Florida |
Lead Sponsor | Collaborator |
---|---|
University of Florida | Lacerta Therapeutics |
United States,
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* Note: There are 29 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety of rAAV9-DES-hGAA vector in LOPD by blood and urine test. | Safety will be tested by clinical pathology tests, blood assay for vector genomes, antibodies against GAA and T-cell ELISPOT against GAA and AAV. | 520 days | |
Secondary | Neurophysiological tests will be performed for neuro function of rAAV9-DES-hGAA vector. | Neurophysiological tests: Surface testing of the common fibular nerve and neuromuscular junction transmission. | 520 days | |
Secondary | Muscle biopsy will be performed for muscular function of rAAV9-DES-hGAA vector. | Muscle biopsy for biochemistry and immunochemistry tests. | 520 days | |
Secondary | Clinical tests will be performed for function of rAAV9-DES-hGAA vector. | Clinical tests: 10 meter walk test and muscle strength test. | 520 days | |
Secondary | Magnetic Resonance Imaging will be performed for visualization of muscle with rAAV9-DES-hGAA vector. | MRI will provide a non-invasive means of evaluating maximum cross-sectional area (CSAmax) - an index of muscle mass - and the MR proton traverse relaxation time (T2) - an index of muscle damage and edema. | 520 days | |
Secondary | Spectroscopy will be performed for function of rAAV9-DES-hGAA vector. | MRS will provide a non-invasive means of evaluating glycogen concentration in muscle. | 520 days |
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