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A Pilot Study of Zavesca® in Patients With Pompe Disease and Infusion Associated Reaction

Primary Purpose

Pompe Disease, Hypersensitivity Reaction

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Zavesca® Prescription
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pompe Disease focused on measuring Pompe Disease, Enzyme Replacement Therapy, Infusion Associated Reaction

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects will be patients between the ages of 18 years and 65 years who have been diagnosed with Pompe Disease, confirmed by mutational analysis and/or GAA enzyme activity assay.

  • Receiving rhGAA ERT
  • Willing to travel to the study site for study assessments
  • Willingness of local medical treatment provider to continue treating study participant with addition of Zavesca® to treatment plan.
  • Willingness of study participant to modify dietary intake on day of infusion *All Subjects will continue enzyme replacement therapy as standard of care, as prescribed by local medical treatment provider during the course of the Study.

Exclusion Criteria:

  • Subject is unable to meet the study requirements
  • Subject's 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
  • Participation in other interventional studies at the time of enrollment that may interfere with this study (at the investigator's discretion)
  • Unable to travel to the University of Florida for study visits

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    Zavesca® 100 mg

    Zavesca® 300 mg

    Arm Description

    3 study participants are given Zavesca® prescription 100 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed. Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.

    3 study participants are given Zavesca® prescription 300 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed. Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.

    Outcomes

    Primary Outcome Measures

    Evaluate Pharmacodynamics of ERT with pre-medication Zavesca
    Change in GAA antibody level from Baseline to week 0: GAA antibody titer is reported at timepoints: pre-infusion, and 6, 12, and 24 hours post-infusion start. Change in GAA antibody level from Baseline to week 6: GAA antibody titer is reported at time points: pre-infusion and post-infusion.

    Secondary Outcome Measures

    Evaluate pharmacokinetics of ERT with pre-medication Zavesca®
    Change in ERT half life at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®). Change in Maximum plasma concentration (Cmax) at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®).
    Evaluate biodistribution of ERT with pre-medication Zavesca®.
    Punch muscle biopsy is performed at week 0 and week 7 for biodistribution: Change in glycogen content and muscle fiber morphology is reported.

    Full Information

    First Posted
    July 1, 2014
    Last Updated
    December 4, 2018
    Sponsor
    University of Florida
    Collaborators
    Amicus Therapeutics
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02185651
    Brief Title
    A Pilot Study of Zavesca® in Patients With Pompe Disease and Infusion Associated Reaction
    Official Title
    A Pilot Study of the Effects of Oral Administration of Zavesca® on Anti-rhGAA Immune Response in Subjects With Pompe Disease Receiving rhGAA Enzyme Replacement Therapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2018
    Overall Recruitment Status
    Terminated
    Why Stopped
    Participants not interested in enrolling.
    Study Start Date
    October 2016 (Actual)
    Primary Completion Date
    July 2018 (Actual)
    Study Completion Date
    July 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Florida
    Collaborators
    Amicus Therapeutics

    4. Oversight

    Data Monitoring Committee
    No

    5. 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 Zavesca® prior to infusion may dampen or eliminate the anti-rhGAA immune response in patients receiving ERT, thereby allowing for greater ERT efficacy. Treatment with Zavesca® before a enzyme replacement therapy (ERT) may decrease the severity of, or eliminate infusion associated reactions (IAR) in people with Pompe Disease receiving ERT.
    Detailed Description
    This Study is designed to assess the effects of Zavesca® as immunomodulatory therapy on anti-rhGAA immune responses in patients with Pompe disease, as well as their health and disease progression. Subjects will either receive Zavesca® at 100 mg or 300 mg dosing levels during study participation (n=3 @ 100 mg dosing; n=3 @ 300 mg dosing). The first 3 subjects enrolled will be prescribed 100 mg Zavesca® 60 minutes prior to ERT infusion. The subsequent 3 subjects enrolled will be prescribed 300 mg Zavesca® 60 minutes to ERT infusion. Eligible participants are on standard ERT for Pompe disease and have a history of infusion associated reaction. Travel to the study site in Gainesville, Florida is required for 3 visits. Participants are prescribed medication Zavesca® and have blood tests, punch muscle biopsy, physical exams, and answer questionnaires over 3 months study participation.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pompe Disease, Hypersensitivity Reaction
    Keywords
    Pompe Disease, Enzyme Replacement Therapy, Infusion Associated Reaction

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    2 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Zavesca® 100 mg
    Arm Type
    Active Comparator
    Arm Description
    3 study participants are given Zavesca® prescription 100 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed. Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.
    Arm Title
    Zavesca® 300 mg
    Arm Type
    Active Comparator
    Arm Description
    3 study participants are given Zavesca® prescription 300 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed. Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.
    Intervention Type
    Drug
    Intervention Name(s)
    Zavesca® Prescription
    Other Intervention Name(s)
    miglustat
    Intervention Description
    Following baseline evaluation, Zavesca® prescription is given. Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.
    Primary Outcome Measure Information:
    Title
    Evaluate Pharmacodynamics of ERT with pre-medication Zavesca
    Description
    Change in GAA antibody level from Baseline to week 0: GAA antibody titer is reported at timepoints: pre-infusion, and 6, 12, and 24 hours post-infusion start. Change in GAA antibody level from Baseline to week 6: GAA antibody titer is reported at time points: pre-infusion and post-infusion.
    Time Frame
    Baseline, week 0, week 6
    Secondary Outcome Measure Information:
    Title
    Evaluate pharmacokinetics of ERT with pre-medication Zavesca®
    Description
    Change in ERT half life at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®). Change in Maximum plasma concentration (Cmax) at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®).
    Time Frame
    Baseline, week 0
    Title
    Evaluate biodistribution of ERT with pre-medication Zavesca®.
    Description
    Punch muscle biopsy is performed at week 0 and week 7 for biodistribution: Change in glycogen content and muscle fiber morphology is reported.
    Time Frame
    Week 0, week 7

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subjects will be patients between the ages of 18 years and 65 years who have been diagnosed with Pompe Disease, confirmed by mutational analysis and/or GAA enzyme activity assay. Receiving rhGAA ERT Willing to travel to the study site for study assessments Willingness of local medical treatment provider to continue treating study participant with addition of Zavesca® to treatment plan. Willingness of study participant to modify dietary intake on day of infusion *All Subjects will continue enzyme replacement therapy as standard of care, as prescribed by local medical treatment provider during the course of the Study. Exclusion Criteria: Subject is unable to meet the study requirements Subject's 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 Participation in other interventional studies at the time of enrollment that may interfere with this study (at the investigator's discretion) Unable to travel to the University of Florida for study visits
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Barry J. Byrne, MD, PhD
    Organizational Affiliation
    University of Florida
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    A Pilot Study of Zavesca® in Patients With Pompe Disease and Infusion Associated Reaction

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