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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

Primary Purpose

Fabry Disease

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
migalastat HCl
Sponsored by
Amicus Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fabry Disease focused on measuring Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate

Eligibility Criteria

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

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Migalastat

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
September 5, 2007
Last Updated
October 1, 2018
Sponsor
Amicus Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00526071
Brief Title
Open-label Long-term Safety Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease Who Have Completed a Previous AT1001 Study
Official Title
Open-label Extension Study to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Why Stopped
The Sponsor (Amicus Therapeutics) terminated this study for logistical reasons.
Study Start Date
September 17, 2007 (Actual)
Primary Completion Date
September 8, 2012 (Actual)
Study Completion Date
September 8, 2012 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Migalastat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
migalastat HCl
Other Intervention Name(s)
AT1001, Galafold, migalastat
Primary Outcome Measure Information:
Title
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Day 1 (after dosing) through EOS (up to 56 months) or follow-up (28 days after EOS)
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline In α-Galactosidase A (α-Gal A) Activity In Leukocytes To Month 42
Description
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.
Time Frame
Baseline, Month 42
Title
Pharmacokinetics Of Migalastat As Assessed By Plasma Concentration
Description
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.
Time Frame
0 (predose on Day 1; start of DEP), 3 hr (postdose at Month 2; during DEP])

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor, Clinical Research
Organizational Affiliation
Amicus Therapeutics
Official's Role
Study Director
Facility Information:
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
78226
Country
United States
City
Parkville
Country
Australia
City
Porto Alegre
Country
Brazil
City
Garches
Country
France
City
London
Country
United Kingdom
City
Salford
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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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