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

September 15, 2011
July 1, 2015
October 2008
October 2018   (final data collection date for primary outcome measure)
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.
Anti-rh GAA antibody titers [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
anti-rh-GAA antibody titers will be evaluated at baseline and every 4-8 weeks for 52 weeks of participation in the primary study. Subjects who continue participation in the extension study (>52 weeks - 3 years, anti-rh-GAA antibody titers will be evaluated every 12 weeks
Complete list of historical versions of study NCT01451879 on ClinicalTrials.gov Archive Site
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)
Safety Labs [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
Safety labs including white count, IgG, CD20 will be evaluated every 4-12 weeks during the primary study and every 12 weeks for subjects who participate in the extension study (>52 weeks - 3 years)
Not Provided
Not Provided
 
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.

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).

Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Residual blood specimens from GAA Ab testing

Non-Probability Sample

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.

Pompe Disease
  • 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
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.
Interventions:
  • Drug: Rituximab
  • Drug: Miglustat
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
25
October 2018
October 2018   (final data collection date for primary outcome measure)

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
Both
up to 65 Years
No
Contact: Lee Ann Lawson, ARNP 352-273-7762 llawson@peds.ufl.edu
United States
 
NCT01451879
IMN 439-2008
No
University of Florida
University of Florida
Not Provided
Principal Investigator: Barry J Byrne, MD, PhD University of Florida
University of Florida
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP