Back to resultsStudy of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
migalastat hydrochloride
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Amicus Therapeutics, AT1001, Migalastat, Pharmacokinetics, Substrate, Galafold
Eligibility Criteria
Inclusion Criteria:
- Male or female between the ages of 16 and 74 diagnosed with Fabry disease.
- Confirmed mutant form of α-galactosidase A shown to be responsive to migalastat in vitro.
- Participant has never been treated with enzyme replacement therapy (ERT) or has not received ERT for 6 consecutive months or longer before the screening visit for the study.
- Urine GL-3 ≥4 times the upper limit of normal at screening.
- Participants taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be on a stable dose for a minimum of 4 weeks before the baseline visit.
- Females who can become pregnant and all males agree to be sexually abstinent or use medically accepted methods of birth control during the study and for 30 days after study completion.
- Participant is willing and able to provide written informed consent and assent, if applicable.
Exclusion Criteria:
- Participant has undergone or is scheduled to undergo kidney transplantation, or is currently on dialysis.
- Estimated glomerular filtration rate <30 milliliters per minute per 1.73 meters squared (chronic kidney disease Stage 4 or 5) based on the Modification of Diet in Renal Disease equation at screening.
- Pregnant or breast-feeding.
- History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol).
- Participant is treated or has been treated with any investigational drug within 30 days of study start.
- Participant is currently treated or has ever been treated with migalastat.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Migalastat
Placebo
Arm Description
Migalastat 150-mg capsule taken orally every other day (QOD) for 6 months and an open-label 6-month treatment extension, followed by an optional, 12-month, open-label treatment extension.
Placebo capsule taken orally QOD for 6 months.
Outcomes
Primary Outcome Measures
Percentage Of Participants With At Least A 50% Reduction From Baseline To Month 6 In The Average Number Of Kidney Interstitial Capillary (IC) Globotriaosylceramide (GL-3) Inclusions
Renal biopsies were taken at Baseline and Month 6 (Stage 1). The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images. A responder was defined as a participant with a ≥50% reduction from Baseline to Month 6 in the average number of kidney IC GL-3 inclusions.
Secondary Outcome Measures
Percent Change In Kidney IC GL-3 Inclusions From Baseline To Month 6
Renal biopsies were taken at Baseline and Month 6. The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images.
Change From Baseline Through Month 24 In Urine GL-3 Levels
The effect of migalastat versus placebo on urine GL-3 levels was measured by liquid chromatography-mass spectrometry/mass spectrometry. The 24-hour urine samples were collected at Baseline, Month 6 (Stage 1), Month 12 (Stage 2), and Month 24 (OLE). Results are presented as changes in nanograms (ng)/mg creatinine from Baseline to the end of the 3 stages.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00925301
Brief Title
Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
Official Title
A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Pharmacodynamics of AT1001 in Patients With Fabry Disease and AT1001-Responsive GLA Mutations
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 23, 2009 (Actual)
Primary Completion Date
June 12, 2012 (Actual)
Study Completion Date
January 29, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amicus Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study was to compare the effect of migalastat (123 milligrams [mg] of migalastat [equivalent to 150 mg of migalastat hydrochloride]) (migalastat) versus placebo on kidney globotriaosylceramide (GL-3).
Detailed Description
This double-blind, randomized, placebo-controlled study was conducted in 67 participants at 46 sites worldwide. The study consisted of 2 stages and an optional open-label treatment extension phase:
Stage 1 included a screening period of up to 2 months followed by a 6-month treatment period which involved 4 visits to the clinic. Participants were randomized in equal proportions to receive either migalastat or placebo.
After completing the 6-month double-blind phase, all participants entered Stage 2 of the study and received migalastat in an open-label manner. Stage 2 treatment lasted for 6 months and involved up to 4 visits to the clinic.
Participants who completed both Stage 1 and Stage 2 of the study as scheduled were offered the opportunity to participate in an open-label treatment extension phase with migalastat. The open-label treatment extension phase lasted 12 months and involved 2 visits to the clinic. A follow-up visit was undertaken 1 month following completion or discontinuation from the open-label treatment extension. Participants completing the 12-month open-label treatment extension and providing consent to enter a separate long-term extension were not required to complete this follow-up visit.
Study assessments included clinical laboratory tests, 12-lead electrocardiogram, kidney biopsy, kidney function testing, echocardiography, and patient-reported outcomes.
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, Migalastat, Pharmacokinetics, Substrate, Galafold
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Sponsor and Assessor were also blinded
Allocation
Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Migalastat
Arm Type
Experimental
Arm Description
Migalastat 150-mg capsule taken orally every other day (QOD) for 6 months and an open-label 6-month treatment extension, followed by an optional, 12-month, open-label treatment extension.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsule taken orally QOD for 6 months.
Intervention Type
Drug
Intervention Name(s)
migalastat hydrochloride
Other Intervention Name(s)
AT1001, Galafold, Migalastat
Intervention Description
Oral capsule QOD
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral capsule QOD
Primary Outcome Measure Information:
Title
Percentage Of Participants With At Least A 50% Reduction From Baseline To Month 6 In The Average Number Of Kidney Interstitial Capillary (IC) Globotriaosylceramide (GL-3) Inclusions
Description
Renal biopsies were taken at Baseline and Month 6 (Stage 1). The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images. A responder was defined as a participant with a ≥50% reduction from Baseline to Month 6 in the average number of kidney IC GL-3 inclusions.
Time Frame
Baseline, Month 6
Secondary Outcome Measure Information:
Title
Percent Change In Kidney IC GL-3 Inclusions From Baseline To Month 6
Description
Renal biopsies were taken at Baseline and Month 6. The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images.
Time Frame
Baseline, Month 6
Title
Change From Baseline Through Month 24 In Urine GL-3 Levels
Description
The effect of migalastat versus placebo on urine GL-3 levels was measured by liquid chromatography-mass spectrometry/mass spectrometry. The 24-hour urine samples were collected at Baseline, Month 6 (Stage 1), Month 12 (Stage 2), and Month 24 (OLE). Results are presented as changes in nanograms (ng)/mg creatinine from Baseline to the end of the 3 stages.
Time Frame
Baseline, Months 6, 12, and 24
Other Pre-specified Outcome Measures:
Title
Change From Month 6 To Month 12 In Average Number Of Kidney IC GL-3 Inclusions
Description
Renal biopsies were taken at Month 6 and Month 12. The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Month 6 and Month 12. Assessments were made using digital images.
Time Frame
Month 6, Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female between the ages of 16 and 74 diagnosed with Fabry disease.
Confirmed mutant form of α-galactosidase A shown to be responsive to migalastat in vitro.
Participant has never been treated with enzyme replacement therapy (ERT) or has not received ERT for 6 consecutive months or longer before the screening visit for the study.
Urine GL-3 ≥4 times the upper limit of normal at screening.
Participants taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be on a stable dose for a minimum of 4 weeks before the baseline visit.
Females who can become pregnant and all males agree to be sexually abstinent or use medically accepted methods of birth control during the study and for 30 days after study completion.
Participant is willing and able to provide written informed consent and assent, if applicable.
Exclusion Criteria:
Participant has undergone or is scheduled to undergo kidney transplantation, or is currently on dialysis.
Estimated glomerular filtration rate <30 milliliters per minute per 1.73 meters squared (chronic kidney disease Stage 4 or 5) based on the Modification of Diet in Renal Disease equation at screening.
Pregnant or breast-feeding.
History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol).
Participant is treated or has been treated with any investigational drug within 30 days of study start.
Participant is currently treated or has ever been treated with migalastat.
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
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49525
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75226
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
City
Springfield
State/Province
Virginia
ZIP/Postal Code
22152
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Buenos Aires
ZIP/Postal Code
B1629ODT
Country
Argentina
City
Adelaide
ZIP/Postal Code
5006
Country
Australia
City
Parkville
ZIP/Postal Code
3050
Country
Australia
City
Porto Alegre
ZIP/Postal Code
90035-903
Country
Brazil
City
Sao Paulo
ZIP/Postal Code
14048-900
Country
Brazil
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4J 1C5
Country
Canada
City
Kobenhavn
ZIP/Postal Code
DK-2100
Country
Denmark
City
Cairo
ZIP/Postal Code
11451
Country
Egypt
City
Garches
ZIP/Postal Code
92380
Country
France
City
Roma
ZIP/Postal Code
00168
Country
Italy
City
Warszawa
ZIP/Postal Code
04-628
Country
Poland
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32994552
Citation
Bichet DG, Aerts JM, Auray-Blais C, Maruyama H, Mehta AB, Skuban N, Krusinska E, Schiffmann R. Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease. Genet Med. 2021 Jan;23(1):192-201. doi: 10.1038/s41436-020-00968-z. Epub 2020 Sep 30. Erratum In: Genet Med. 2020 Nov 20;:
Results Reference
derived
PubMed Identifier
30723321
Citation
Germain DP, Nicholls K, Giugliani R, Bichet DG, Hughes DA, Barisoni LM, Colvin RB, Jennette JC, Skuban N, Castelli JP, Benjamin E, Barth JA, Viereck C. Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study. Genet Med. 2019 Sep;21(9):1987-1997. doi: 10.1038/s41436-019-0451-z. Epub 2019 Feb 6.
Results Reference
derived
PubMed Identifier
29703262
Citation
Schiffmann R, Bichet DG, Jovanovic A, Hughes DA, Giugliani R, Feldt-Rasmussen U, Shankar SP, Barisoni L, Colvin RB, Jennette JC, Holdbrook F, Mulberg A, Castelli JP, Skuban N, Barth JA, Nicholls K. Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial. Orphanet J Rare Dis. 2018 Apr 27;13(1):68. doi: 10.1186/s13023-018-0813-7.
Results Reference
derived
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
27509102
Citation
Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.
Results Reference
derived
Learn more about this trial
Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
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