Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies

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

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.

Study Overview

• Status: Completed
• Conditions: Pompe Disease
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 11

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-rh GAA antibody titers	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.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B-lymphocyte antigen (CD20) level	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)	52 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Barry J Byrne, MD, PhD, University of Florida

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2008
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: October 11, 2011
• First Posted (Estimate): October 14, 2011

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Pompe Disease; Infusion Associated Reaction; Immune-modulation regimen
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Glycoside Hydrolase Inhibitors; Rituximab; Miglustat
• Other Study ID Numbers: IRB201602404; IMN 439-2008 (Other Identifier: Legacy study)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No