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Open-label Long-term Safety Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease Who Have Completed a Previous AT1001 Study

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ClinicalTrials.gov Identifier: NCT00526071
Recruitment Status : Terminated (The Sponsor (Amicus Therapeutics) terminated this study for logistical reasons.)
First Posted : September 6, 2007
Results First Posted : October 3, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Brief Summary:
Study to evaluate the long-term safety, tolerability, and pharmacodynamics (PD) of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: migalastat HCl Phase 2

Detailed Description:

This was a long-term open-label study of migalastat in participants with Fabry disease who were previously enrolled in a Phase 2 study of migalastat (FAB-CL-201 [NCT00214500], FAB-CL-202 [NCT00283959], FAB-CL-203 [NCT00283933], or FAB-CL-204 [NCT00304512]). Participants could enter this extension study immediately upon completion of participation in their previous study of migalastat, or at a later time point. Thus, some participants did not necessarily have continuous treatment with migalastat from the end of the original study to the time of enrollment into this extension study. Participants who enrolled before Protocol Amendment 2 received migalastat 150 milligrams (mg) orally once every other day (QOD). After the amendment, these participants entered a dose escalation period (DEP) at their next scheduled visit. During the DEP, participants received migalastat 250 mg (once daily [QD] for 3 days and 4 days off per week) for the first 2 months. If there were no safety concerns, the dose was then increased to 500 mg QD for 3 days and 4 days off per week). Participants received 500 mg (QD for 3 days and 4 days off per week) for up to 10 months, depending on the approval date of the protocol amendments at each site. An interim review of safety and PD data was performed after all enrolled participants had completed at least 4 months of treatment in the DEP. After the review, the dose and regimen of migalastat was returned to 150 mg QOD for all participants, except those who were on another dose as previously agreed by the investigator and medical monitor.

The sponsor (Amicus Therapeutics) discontinued Study FAB-CL-205 for logistical reasons and not due to either safety concerns or lack of efficacy. Participants who were ongoing in Study FAB-CL-205 at the time of discontinuation were offered participation in another open-label, long-term treatment study of migalastat (AT1001-041 [NCT01458119]). Participants who did not enroll in Study AT1001-041 were contacted by telephone or another suitable method approximately 1 month after the End of Study (EOS) visit to inquire about adverse events and concomitant medications.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label Extension Study to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Actual Study Start Date : September 17, 2007
Actual Primary Completion Date : September 8, 2012
Actual Study Completion Date : September 8, 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Migalastat
Migalastat was administered orally, 150 mg QOD, 250 mg QD for 3 days, 4 days off per week for 2 months, or 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. Participants received migalastat for up to 56 months.
Drug: migalastat HCl
Other Names:
  • AT1001
  • Galafold
  • migalastat




Primary Outcome Measures :
  1. Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after dosing) through EOS (up to 56 months) or follow-up (28 days after EOS) ]
    A TEAE was defined as any adverse event (AE) with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through End of Study (EOS) or follow-up (for participants who did not enroll in Study AT1001-041) are presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.


Secondary Outcome Measures :
  1. Absolute Change From Baseline In α-Galactosidase A (α-Gal A) Activity In Leukocytes To Month 42 [ Time Frame: Baseline, Month 42 ]
    The activity of the α-Gal A enzyme was measured in leukocyte lysate by a validated fluorometric assay method, using 4-methylumbelliferone as a reference. The activity values obtained were normalized to protein (measured using a colorimetric assay). Baseline was defined as the last non-missing pre-treatment value for each participant in his or her respective preceding migalastat Phase 2 study. A negative change from Baseline indicates that α-Gal A activity decreased. α-Gal A activity levels are presented for Baseline and Month 42.

  2. Pharmacokinetics Of Migalastat As Assessed By Plasma Concentration [ Time Frame: 0 (predose on Day 1; start of DEP), 3 hr (postdose at Month 2; during DEP]) ]
    The concentration of migalastat was evaluated in plasma following a dose of 250 mg and 500 mg. Blood samples were taken at trough (predose or Time 0; just prior to the third dose during a 3 day on, 4 days off dosing regimen) and at peak (3 hr postdose; after the third dose during a 3 day on, 4 days off dosing regimen) during the Day 1 (250 mg) and Month 2 (500 mg) visits. This outcome presents the lowest and highest concentrations of migalastat measured in any of the participants for predose and 3 hr postdose.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have completed another Phase 2 study of migalastat in Fabry Disease
  • Women of childbearing potential must have had a negative result on their pregnancy test
  • Male and female participants agreed to use a reliable method of contraception during study treatment and for 4 weeks after study treatment termination
  • Were willing and able to provide written informed consent

Exclusion Criteria:

  • Had not completed a Phase 2 study of migalastat in Fabry Disease
  • Had a major protocol violation in the preceding migalastat trial and was discontinued
  • Had undergone or was scheduled to undergo kidney transplantation or was currently on dialysis
  • Had been treated with another investigational drug (except migalastat) within 30 days of study start
  • Had been treated with Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), or Zavesca® (miglustat) within 2 weeks prior to enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00526071


Locations
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United States, Georgia
Decatur, Georgia, United States, 30033
United States, New York
New York, New York, United States, 10016
United States, Texas
Dallas, Texas, United States, 78226
Australia
Parkville, Australia
Brazil
Porto Alegre, Brazil
France
Garches, France
United Kingdom
London, United Kingdom
Salford, United Kingdom
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Medical Monitor, Clinical Research Amicus Therapeutics

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00526071     History of Changes
Other Study ID Numbers: FAB-CL-205
First Posted: September 6, 2007    Key Record Dates
Results First Posted: October 3, 2018
Last Update Posted: October 3, 2018
Last Verified: October 2018

Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
AT1001
Galafold
Migalastat
Substrate

Additional relevant MeSH terms:
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Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
1-Deoxynojirimycin
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action