Clinical trial NCT01451879: Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies
Official title: Effects of Immunomodulation Therapy on Anti-rhGAA Immune Response in Subjects With Pompe Disease Receiving rhGAA Enzyme Replacement Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pompe Disease
Keywords: Pompe Disease
Infusion Associated Reaction
Immune-modulation regimen
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2011-10-14
Enrollment: 11
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of male and female patients age 0-65 years, with a diagnosis of early-onset Pompe Disease. Up to 25 subjects will be enrolled.

Brief summary: Hypothesis: the effectiveness of treatment of Pompe Disease with rhGAA enzyme replacement therapy (ERT) is limited at least in part because patients develop antibodies against the provided rhGAA enzyme. Treatment with immunomodulatory drugs may dampen or eliminate the anti-rhGAA immune response in patients receiving ERT, thereby allowing for greater ERT efficacy. Studying the immune response to rhGAA may provide valuable insight into the role of the immune system in the effectiveness of ERT for Pompe Disease.

Detailed description: The purpose of this research study is to determine the effect(s) of medications that alter the immune system on anti-rhGAA immune response in Pompe patients receiving rhGAA enzyme replacement therapy (ERT). The investigators would also like to determine whether treating Pompe Disease with medications that affect the immune system has any effects on the overall health or disease progression of Pompe.

Subjects will be patients between the ages of 0 months and 65 years who have been diagnosed with Pompe Disease, confirmed by mutational analysis and/or GAA enzyme activity assay.

Subjects will be eligible regardless of whether they have begun enzyme replacement therapy prior to enrollment. All Subjects will receive enzyme replacement therapy as standard of care during the course of the Study, although they may not have begun ERT treatment at the time of enrollment. In addition to ERT, subjects may receive an immunomodulatory regimen as part of their standard of care; this may include rituximab, sirolimus, methotrexate, IVIg or other immunomodulatory agents such as pharmacological chaperone N-butyldeoxynojirimycin (NB-DNJ), alone or in combination, at the discretion of their caregiver(s).

Eligibility criteria: Inclusion Criteria:

* patients between the ages of 0 months and 65 years
* diagnosed with early-onset Pompe Disease, confirmed by mutational analysis and/or GAA enzyme assay
* eligible regardless of whether they have begun enzyme replacement therapy prior to enrollment
* all subjects will receive ERT as standard of care during the course of the study, although they may not have begun ERT treatment at the time of enrollment
* subjects may receive an immunomodulatory regimen as part of their standard of care; this may include rituximab, sirolimus, methotrexate, Gamunex, Hizentra, Zavesca or other immunomodulatory agents, alone or in combination, at the discretion of their caregiver(s)

Exclusion Criteria:

* subject is unable to meet the study requirements
* subjects medical condition contraindicates participation or Study Investigators feel that participation is otherwise not in the subject's best interest
* subject does not receive ERT treatment

Primary outcomes:
measure: Anti-rh GAA antibody titers
timeFrame: 52 weeks
Secondary outcomes:
measure: B-lymphocyte antigen (CD20) level
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Barry J Byrne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elder ME, Nayak S, Collins SW, Lawson LA, Kelley JS, Herzog RW, Modica RF, Lew J, Lawrence RM, Byrne BJ. B-Cell depletion and immunomodulation before initiation of enzyme replacement therapy blocks the immune response to acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr. 2013 Sep;163(3):847-54.e1. doi: 10.1016/j.jpeds.2013.03.002. Epub 2013 Apr 16.