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

Phase 2

Terminated

• Conditions: Fabry Disease
• Interventions: Drug: migalastat HCl

• Registration Number: NCT00526071
• Lead Sponsor: 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

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 Timeline

• Study First Submitted: 2007-09-05
• Study First Submitted QC: 2007-09-05
• Study First Posted: 2007-09-06
• Study Start: 2007-09-17
• Primary Completion: 2012-09-08
• Study Completion: 2012-09-08
• Disposition First Submitted: 2013-07-18
• Disposition First Submitted QC: 2013-07-18
• Disposition First Posted: 2013-07-22
• Results First Submitted: 2018-01-09
• Status Verified: 2018-10
• Results First Submitted QC: 2018-10-01
• Last Update Submitted: 2018-10-01
• Results First Posted: 2018-10-03
• Last Update Posted: 2018-10-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Migalastat	migalastat HCl	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.

Primary Outcome Measures

Name	Time	Method
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)	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

Name	Time	Method
Absolute Change From Baseline In α-Galactosidase A (α-Gal A) Activity In Leukocytes To Month 42	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.
Pharmacokinetics Of Migalastat As Assessed By Plasma Concentration	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.