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Trial record 22 of 103 for:    Pompe Disease

Safety Study of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase to Treat Pompe Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00976352
Recruitment Status : Completed
First Posted : September 14, 2009
Results First Posted : November 17, 2017
Last Update Posted : September 14, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE July 13, 2009
First Posted Date  ICMJE September 14, 2009
Results First Submitted Date  ICMJE June 1, 2017
Results First Posted Date  ICMJE November 17, 2017
Last Update Posted Date September 14, 2018
Actual Study Start Date  ICMJE September 2010
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2017)
Safety Assessments of the rAAV1-CMV-GAA (Study Agent), Changes Post Study Agent Administration. [ Time Frame: Change from baseline to 365 post study agent administration. ]
Change in Adeno-associated virus (AAV) antibody level; Change in Alglucosidase alpha (GAA) Antibody level
Original Primary Outcome Measures  ICMJE
 (submitted: September 11, 2009)
Assessment of the safety of intramuscular administration of a recombinant adeno-associated virus, rAAV1-CMV-GAA, vector in children with ventilator-dependent Pompe disease. [ Time Frame: Days 1, 2, 3, 14, 30, 60 90, and 180 of the trial ]
Change History Complete list of historical versions of study NCT00976352 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2017)
  • Maximal Inspiratory Pressure [ Time Frame: Baseline and 365 post study agent administration ]
    Median (range) Maximal Inspiratory Pressure (MIP), in cm H2O
  • Evaluation of Ventilatory Performance Benefit of rAAV1-CMV-GAA Gene Transfer and Respiratory Muscle Strength Training (RMST) Compared to RMST Alone. [ Time Frame: Screening, Baseline, and 365 post study agent administration. ]
    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.
  • Evaluation of Tidal Volume Benefit of rAAV1-CMV-GAA Gene Transfer and Respiratory Muscle Strength Training, Compared to Respiratory Muscle Strength Training Alone. [ Time Frame: Screening, Baseline, and Day 365 post study agent administration ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2009)
Determination of the dose of rAAV1-CMV-GAA vector required to achieve diaphragm transduction and restoration of GAA activity in the diaphragm. [ Time Frame: 14 and 90 days post injection ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase to Treat Pompe Disease
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:
Open label study
Primary Purpose: Treatment
Condition  ICMJE Pompe Disease
Intervention  ICMJE
  • Drug: rAAV1-CMV-GAA (study agent) Administration
    rAAV1-CMV-GAA via intramuscular injection into the diaphragm. Dose selection for cohort 1: 1.0 x 10e12 vector genomes Cohort 1 will have a total of 3 participants enrolled. Dose selection for cohort 2 and 3: 5.0 x 10e12 vector genomes rAAV1-CMV-GAA. Cohort 2 = 6 subjects.
    Other Names:
    • Gene transfer
    • study agent (rAAV1-CMV-GAA)
  • Other: RMST
    After enrollment and screening visit, the subject will be given a RMST prescription and will complete RMST for a minimum of 4 weeks prior to study agent administration. RMST prescription will be adjusted as needed at Day 14, 90, 180, and 270.
    Other Name: Respiratory Muscle Strength Training
Study Arms  ICMJE
  • Experimental: rAAV1-CMV-GAA administration-cohort 1
    rAAV1-CMV-GAA (study agent) Administration: 1.0 x 10e12 vector genomes. The following study assessments/interventions will be completed: Respiratory Muscle Strength Training (RMST), Safety labs, pulmonary function testing.
    Interventions:
    • Drug: rAAV1-CMV-GAA (study agent) Administration
    • Other: RMST
  • Experimental: rAAV1-CMV-GAA administration-cohort 2
    rAAV1-CMV-GAA (study agent) Administration: 5.0 x 10e12 vector genomes Cohort 2 = 6 subjects. The following study assessments/interventions will be completed: Respiratory Muscle Strength Training (RMST), Safety labs, pulmonary function testing.
    Interventions:
    • Drug: rAAV1-CMV-GAA (study agent) Administration
    • Other: RMST
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2015)
9
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2009)
6
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00976352
Other Study ID Numbers  ICMJE PGTC PD-AAV004-N
P01HL059412-06 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Barry J Byrne, MD, PhD University of Florida
Principal Investigator: Shelley Collins, MD University of Florida
PRS Account University of Florida
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP