Back to resultsA 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
migalastat HCl
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate
Eligibility Criteria
Inclusion Criteria: Males between 18 and 65 years of age (inclusive) Hemizygous for Fabry disease Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial) Had enhanceable enzyme activity based on in vitro tests Had documented evidence of cardiac and/or renal dysfunction (for example, abnormal electrocardiogram (ECG), left ventricular hypertrophy, renal insufficiency) and/or cerebral tissue dysfunction documented by evidence of stroke and/or peripheral nervous tissue dysfunction (for example, intolerance to heat/cold, decrease of perspiration) Must have been previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease or were able to stop ERT for at least 18 weeks or up to three months, and be willing to undergo two kidney and three skin biopsies Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study Were willing and able to sign an informed consent form Exclusion Criteria: History of significant disease other than Fabry disease History of organ transplant Serum creatinine >2 mg per deciliter on Day -2 Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds prior to dosing Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning Took any of the following prohibited medications: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication Participated in a previous clinical trial in the last 30 days Any other condition, which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Migalastat
Arm Description
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week extension period.
Outcomes
Primary Outcome Measures
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as any adverse event with a 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 adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented.
A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Secondary Outcome Measures
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
PBMCs were isolated from whole blood and lysed, and α-Gal A activity was measured by a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hour [hr]) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat.
α-Gal A activity in PBMCs are presented by individual participants. Values of "0" presented below represent α-Gal A activity levels that were below the lower limit of quantification.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00283959
Brief Title
A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Official Title
A Phase 2, Open-Label, Single Dose Level, 12-Week Study to Evaluate the 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
Completed
Study Start Date
June 27, 2006 (Actual)
Primary Completion Date
May 8, 2008 (Actual)
Study Completion Date
May 8, 2008 (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 safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) and how migalastat works in participants with Fabry disease.
Detailed Description
This was a Phase 2, open-label study in male participants with Fabry disease. The study consisted of a 4-week screening period during which participants' genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat via an in vitro assay. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 12-week treatment period, followed by an optional 36-week extension period. Participants received migalastat 150 milligrams (mg) once every other day (QOD) for 12 weeks during the treatment period. Participants could then opt to participate in the extension period.
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
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Migalastat
Arm Type
Experimental
Arm Description
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week extension period.
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
TEAEs were defined as any adverse event with a 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 adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented.
A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame
Day 1 (after dosing) through Week 48 (end of extension period)
Secondary Outcome Measure Information:
Title
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Description
PBMCs were isolated from whole blood and lysed, and α-Gal A activity was measured by a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hour [hr]) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat.
α-Gal A activity in PBMCs are presented by individual participants. Values of "0" presented below represent α-Gal A activity levels that were below the lower limit of quantification.
Time Frame
Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males between 18 and 65 years of age (inclusive)
Hemizygous for Fabry disease
Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
Had enhanceable enzyme activity based on in vitro tests
Had documented evidence of cardiac and/or renal dysfunction (for example, abnormal electrocardiogram (ECG), left ventricular hypertrophy, renal insufficiency) and/or cerebral tissue dysfunction documented by evidence of stroke and/or peripheral nervous tissue dysfunction (for example, intolerance to heat/cold, decrease of perspiration)
Must have been previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease or were able to stop ERT for at least 18 weeks or up to three months, and be willing to undergo two kidney and three skin biopsies
Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study
Were willing and able to sign an informed consent form
Exclusion Criteria:
History of significant disease other than Fabry disease
History of organ transplant
Serum creatinine >2 mg per deciliter on Day -2
Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds prior to dosing
Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
Took any of the following prohibited medications: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
Participated in a previous clinical trial in the last 30 days
Any other condition, which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results
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
Parkville
Country
Australia
City
Porto Alegre
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
27657681
Citation
Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22.
Results Reference
derived
PubMed Identifier
23176611
Citation
Germain DP, Giugliani R, Hughes DA, Mehta A, Nicholls K, Barisoni L, Jennette CJ, Bragat A, Castelli J, Sitaraman S, Lockhart DJ, Boudes PF. Safety and pharmacodynamic effects of a pharmacological chaperone on alpha-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies. Orphanet J Rare Dis. 2012 Nov 24;7:91. doi: 10.1186/1750-1172-7-91.
Results Reference
derived
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A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
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