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Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease

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ClinicalTrials.gov Identifier: NCT00925301
Recruitment Status : Completed
First Posted : June 22, 2009
Results First Posted : October 30, 2018
Last Update Posted : October 30, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

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).

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: migalastat hydrochloride Drug: Placebo Phase 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Sponsor and Assessor were also blinded
Primary Purpose: Treatment
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
Actual Study Start Date : October 23, 2009
Actual Primary Completion Date : June 12, 2012
Actual Study Completion Date : January 29, 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Migalastat
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.
Drug: migalastat hydrochloride
Oral capsule QOD
Other Names:
  • AT1001
  • Galafold
  • Migalastat

Placebo Comparator: Placebo
Placebo capsule taken orally QOD for 6 months.
Drug: Placebo
Oral capsule QOD




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline, Month 6 ]
    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 :
  1. Percent Change In Kidney IC GL-3 Inclusions From Baseline To Month 6 [ Time Frame: Baseline, 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.

  2. Change From Baseline Through Month 24 In Urine GL-3 Levels [ Time Frame: Baseline, Months 6, 12, and 24 ]
    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.


Other Outcome Measures:
  1. Change From Month 6 To Month 12 In Average Number Of Kidney IC GL-3 Inclusions [ Time Frame: Month 6, Month 12 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 74 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00925301


  Hide Study Locations
Locations
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United States, California
Los Angeles, California, United States, 90048
San Francisco, California, United States, 94143
United States, Georgia
Decatur, Georgia, United States, 30033
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Michigan
Grand Rapids, Michigan, United States, 49525
United States, New York
New York, New York, United States, 10032
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Dallas, Texas, United States, 75226
United States, Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
Springfield, Virginia, United States, 22152
United States, Washington
Seattle, Washington, United States, 98195
Argentina
Buenos Aires, Argentina, B1629ODT
Australia
Adelaide, Australia, 5006
Parkville, Australia, 3050
Brazil
Porto Alegre, Brazil, 90035-903
Sao Paulo, Brazil, 14048-900
Canada, Quebec
Montreal, Quebec, Canada, H4J 1C5
Denmark
Kobenhavn, Denmark, DK-2100
Egypt
Cairo, Egypt, 11451
France
Garches, France, 92380
Italy
Roma, Italy, 00168
Poland
Warszawa, Poland, 04-628
Spain
Barcelona, Spain, 08025
Zaragoza, Spain, 50009
Turkey
Ankara, Turkey, 06500
United Kingdom
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Medical Monitor, Clinical Research Amicus Therapeutics

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00925301     History of Changes
Other Study ID Numbers: AT1001-011
FACETS ( Other Identifier: Amicus Therapeutics )
2009-013459-31 ( EudraCT Number )
First Posted: June 22, 2009    Key Record Dates
Results First Posted: October 30, 2018
Last Update Posted: October 30, 2018
Last Verified: October 2018
Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
AT1001
Migalastat
Pharmacokinetics
Substrate
Galafold
Additional relevant MeSH terms:
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Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
1-Deoxynojirimycin
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action