Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies

Completed

• Conditions: Pompe Disease
• Interventions: Drug: Rituximab; Drug: Miglustat

• Registration Number: NCT01451879
• Lead Sponsor: University of Florida

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).

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2011-09-15
• Study First Submitted QC: 2011-10-11
• Study First Posted: 2011-10-14
• Primary Completion: 2017-10
• Study Completion: 2017-10
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-06
• Last Update Posted: 2017-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Age 0 months to 65 years	Miglustat	Confirmed diagnosis of Pompe Disease, and clinically prescribed immune modulation regimen with agents such as rituximab, sirolimus, methotrexate, IVIg or other immunomodulatory agents such as pharmacological chaperone Miglustat, N-butyldeoxynojirimycin (NB-DNJ), alone or in combination, at the discretion of their primary/specialist caregiver.
Age 0 months to 65 years	Rituximab	Confirmed diagnosis of Pompe Disease, and clinically prescribed immune modulation regimen with agents such as rituximab, sirolimus, methotrexate, IVIg or other immunomodulatory agents such as pharmacological chaperone Miglustat, N-butyldeoxynojirimycin (NB-DNJ), alone or in combination, at the discretion of their primary/specialist caregiver.

Primary Outcome Measures

Name	Time	Method
Anti-rh GAA antibody titers	52 weeks	Antibody titer for anti-rh-GAA will be evaluated at baseline and every 4-8 weeks for 52 weeks of participation in the primary study. For subjects who continue participation in the extension study (\>52 weeks - 5 years), anti-rh-GAA antibody titers will be evaluated every 12 - 24 weeks.

Secondary Outcome Measures

Name	Time	Method
B-lymphocyte antigen (CD20) level	52 weeks	Reports from clinical lab: B-lymphocyte antigen (CD20) will be added to the study record when available every 4-12 weeks during the primary study and every 12 weeks for subjects who participate in the extension study (\>52 weeks - 6 years)

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Gainesville, Florida, United States