Safety Study of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase to Treat Pompe Disease
| Status: | Completed |
|---|---|
| Conditions: | Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 2 - 18 |
| Updated: | 9/16/2018 |
| Start Date: | September 2010 |
| End Date: | December 2015 |
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
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.
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.
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.
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.
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.
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