Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies

NCT01451879 | Completed

• 2 other identifiers: IRB201602404IMN 439-2008
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Pompe Disease

Keywords

Pompe Disease; Infusion Associated Reaction; Immune-modulation regimen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• B-lymphocyte antigen (CD20) level

  52 weeks

Study Arms (1)

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; Drug: Miglustat

Interventions

Rituximab DRUG

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

Also known as: Rituxan, MabThera, Zytux

Age 0 months to 65 years

Miglustat DRUG

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

Also known as: Zavesca, N-butyldeoxynojirimaycin, Mulberry extract

Age 0 months to 65 years

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (1)

• 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.

  PMID: 23601496 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Residual blood specimens from GAA Ab testing

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

Rituximab; miglustat; Morus alba

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Barry J Byrne, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: October 14, 2011
• Study Start: October 1, 2008
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: December 8, 2017

Record last verified: 2017-12

Locations

US (1)