Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by University of Florida
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01451879
First received: September 15, 2011
Last updated: July 1, 2015
Last verified: July 2015
  Purpose

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 Intervention
Pompe Disease
Drug: Rituximab
Drug: Miglustat

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Anti-rh GAA antibody titers [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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)


Biospecimen Retention:   Samples With DNA

Residual blood specimens from GAA Ab testing


Estimated Enrollment: 25
Study Start Date: October 2008
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451879

Contacts
Contact: Lee Ann Lawson, ARNP 352-273-7762 llawson@peds.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Lee Ann Lawson, ARNP    352-273-7762    llawson@pedcard.ufl.edu   
Contact: Grace Thompson, BS    352-273-8218      
Principal Investigator: Barry J. Byrne, MD, PhD         
Sub-Investigator: Melissa Elder, MD PhD         
Sub-Investigator: Shelley Collins, MD         
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Barry J Byrne, MD, PhD University of Florida
  More Information

Publications:
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01451879     History of Changes
Other Study ID Numbers: IMN 439-2008
Study First Received: September 15, 2011
Last Updated: July 1, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Pompe Disease
Infusion Associated Reaction
Immune-modulation regimen

Additional relevant MeSH terms:
Glycogen Storage Disease Type II
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Carbohydrate Metabolism, Inborn Errors
Central Nervous System Diseases
Genetic Diseases, Inborn
Glycogen Storage Disease
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Miglustat
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015