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

Open-label Extension Study to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of AT1001 in Patients With Fabry Disease

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

Study Overview

• Status: Terminated
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: migalastat HCl

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia
• Brazil
  • Porto Alegre, Brazil
• France
  • Garches, France
• United Kingdom
  • London, United Kingdom
  • Salford, United Kingdom
• United States
  • Georgia
    • Decatur, Georgia, United States, 30033
  • New York
    • New York, New York, United States, 10016
  • Texas
    • Dallas, Texas, United States, 78226

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)	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.	Day 1 (after dosing) through EOS (up to 56 months) or follow-up (28 days after EOS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline In α-Galactosidase A (α-Gal A) Activity In Leukocytes To 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.	Baseline, Month 42
Pharmacokinetics Of Migalastat As Assessed By Plasma Concentration	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.	0 (predose on Day 1; start of DEP), 3 hr (postdose at Month 2; during DEP])

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2007
• Primary Completion (Actual): September 8, 2012
• Study Completion (Actual): September 8, 2012

Study Registration Dates

• First Submitted: September 5, 2007
• First Submitted That Met QC Criteria: September 5, 2007
• First Posted (Estimate): September 6, 2007

Study Record Updates

• Last Update Posted (Actual): October 3, 2018
• Last Update Submitted That Met QC Criteria: October 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Amicus Therapeutics; AT1001; Galafold; Migalastat; Substrate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: FAB-CL-205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No