Pompe Disease Clinical Trial
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
Verified date | September 2018 |
Source | University of Florida |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 9 |
Est. completion date | December 2015 |
Est. primary completion date | December 2015 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years to 18 Years |
Eligibility |
Inclusion Criteria: - Male or female subjects 2-18 years of age. - Have a diagnosis of Pompe, as defined by protein assay, DNA sequence of the acid alpha-glucosidase gene and clinical symptoms of the disease. - Using assisted ventilation at baseline. Mechanical Ventilation is defined as any use of ventilation support, (including but not limited to BiPAP, CPAP), a minimum of 1 hours per day. - 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. Exclusion Criteria: The subject must not: - Have required acute, as distinguished from long-term, maintenance or chronic suppressive, oral or intravenous antibiotic therapy for a respiratory infection within 15 days prior to baseline screening. - Have required oral or systemic corticosteroids within the last 15 days prior to baseline screening. - Have a platelet count less than 75,000/ cu mm. - Have an INR greater than 1.3. - Serological evidence of hepatitis B, hepatitis C, or HIV positive. - Be currently or within the past 30 days participating in any other research protocol involving investigational agents or therapies. - Have received gene transfer agents within the past 6 months. - 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 any other concurrent condition which, in the opinion of the investigator, would make the subject unsuitable for the study. |
Country | Name | City | State |
---|---|---|---|
United States | Shands at the University of Florida | Gainesville | Florida |
Lead Sponsor | Collaborator |
---|---|
University of Florida | National Heart, Lung, and Blood Institute (NHLBI) |
United States,
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Pauly DF, Fraites TJ, Toma C, Bayes HS, Huie ML, Hirschhorn R, Plotz PH, Raben N, Kessler PD, Byrne BJ. Intercellular transfer of the virally derived precursor form of acid alpha-glucosidase corrects the enzyme deficiency in inherited cardioskeletal myopathy Pompe disease. Hum Gene Ther. 2001 Mar 20;12(5):527-38. — View Citation
Smith BK, Collins SW, Conlon TJ, Mah CS, Lawson LA, Martin AD, Fuller DD, Cleaver BD, Clément N, Phillips D, Islam S, Dobjia N, Byrne BJ. Phase I/II trial of adeno-associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respi — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety Assessments of the rAAV1-CMV-GAA (Study Agent), Changes Post Study Agent Administration. | Change in Adeno-associated virus (AAV) antibody level; Change in Alglucosidase alpha (GAA) Antibody level | Change from baseline to 365 post study agent administration. | |
Secondary | Maximal Inspiratory Pressure | Median (range) Maximal Inspiratory Pressure (MIP), in cm H2O | Baseline and 365 post study agent administration | |
Secondary | Evaluation of Ventilatory Performance Benefit of rAAV1-CMV-GAA Gene Transfer and Respiratory Muscle Strength Training (RMST) Compared to RMST Alone. | Median (range) maximal inspiratory pressure, in cm H2O. Timeframe for RMST training was 90 days prior to rAAV1-CMV-GAA gene transfer. Timeframe for following subjects after rAAV1-CMV-GAA gene transfer was 365 days. | Screening, Baseline, and 365 post study agent administration. | |
Secondary | Evaluation of Tidal Volume Benefit of rAAV1-CMV-GAA Gene Transfer and Respiratory Muscle Strength Training, Compared to Respiratory Muscle Strength Training Alone. | Best effort tidal volume, referenced to body mass, without use of ventilator assistance. Timeframe for respiratory muscle strength training alone was 90 days prior to dosing, timeframe post adminstration of rAAV1-CMV-GAA was 365 days. | Screening, Baseline, and Day 365 post study agent administration |
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