Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies

Sponsor

University of Florida (Other)

Overall Status

Completed

CT.gov ID

NCT01451879

Collaborator

(none)

Enrollment

Location

108

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pompe Disease	Drug: Rituximab Drug: Miglustat

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 Design

Study Type:

Observational

Actual Enrollment :

11 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Effects of Immunomodulation Therapy on Anti-rhGAA Immune Response in Subjects With Pompe Disease Receiving rhGAA Enzyme Replacement Therapy

Actual Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Oct 1, 2017

Actual Study Completion Date :

Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Age 0 months to 65 years 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.	Drug: Rituximab Clinically prescribed immune modulation regimen dosage determined by local medical provider. Other Names: Rituxan MabThera Zytux Drug: Miglustat Clinically prescribed immune modulation regimen dosage determined by local medical provider. Other Names: Zavesca N-butyldeoxynojirimaycin Mulberry extract

Arm

Intervention/Treatment

Age 0 months to 65 years

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.

Drug: Rituximab

Clinically prescribed immune modulation regimen dosage determined by local medical provider.

Other Names:

Rituxan

MabThera

Zytux

Drug: Miglustat

Clinically prescribed immune modulation regimen dosage determined by local medical provider.

Other Names:

Zavesca

N-butyldeoxynojirimaycin

Mulberry extract

Outcome Measures

Primary Outcome Measures

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

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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