Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease - Full Text View

Purpose

The purpose of this study is to compare the effect of AT1001 (migalastat hydrochloride) versus placebo on kidney GL-3.

Condition	Intervention	Phase
Fabry Disease	Drug: migalastat hydrochloride Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) 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

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Fabry disease Farber lipogranulomatosis Schindler disease succinic semialdehyde dehydrogenase deficiency

U.S. FDA Resources

Further study details as provided by Amicus Therapeutics:

Primary Outcome Measures:

kidney GL-3 (assessed histologically in kidney biopsy samples) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

urine GL-3 levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
renal function (assessed by iohexol GFR, eGFR, and 24-hour urine protein) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
safety and tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	August 2009
Estimated Study Completion Date:	January 2014
Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AT1001 Oral Capsule AT1001	Drug: migalastat hydrochloride oral capsule every other day Other Name: AT1001
Placebo Comparator: Placebo Oral Capsule Placebo	Drug: Placebo oral capsule every other day Other Name: Placebo

Detailed Description:

This double-blind, randomized, placebo-controlled study will be conducted in 60 patients at approximately 40 sites worldwide. The study will consist of two stages and an open-label treatment extension phase:

Stage 1 includes a screening period of up to 2 months followed by a 6-month treatment period which will involve 4 visits to the clinic. Patients will be randomized in equal proportions to receive either AT1001 or placebo.

After completing the 6-month double-blind phase, all patients will enter Stage 2 of the study and receive AT1001 in an open-label manner. Stage 2 treatment will last for 6 months and will involve 4 visits to the clinic.

Subjects who complete both Stage 1 and Stage 2 of the study as scheduled may be offered the opportunity to participate in a an open-label treatment extension phase with AT1001. The open-label treatment extension phase will last 13 months and will involve 3 visits to the clinic.

Study assessments will include clinical laboratory tests, 12-lead ECG, kidney biopsy, kidney function testing, echocardiography, and patient reported outcomes.

Eligibility

Ages Eligible for Study:	16 Years to 74 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female between the ages of 16 and 74 diagnosed with Fabry disease
Confirmed GLA mutation that has been shown to be responsive to AT1001 in vitro
Subject has never been treated with ERT or has not received ERT for 6 consecutive months or longer before the screening visit for the study
Urine GL-3 greater than or equal to four times the upper limit of normal at Screening
Subjects taking angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) must be on a stable dose for a minimum of 4 weeks before the baseline visit
Women who can become pregnant and all men agree to be sexually abstinent or use medically accepted methods of birth control during the study and for 30 days after study completion
Subject is willing and able to provide written informed consent, and assent if applicable

Exclusion Criteria:

Subject has undergone or is scheduled to undergo kidney transplantation, or is currently on dialysis
eGFR < 30 mL/min/1.73m2 (CKD Stage 4 or 5) based on MDRD equation
QTc ≥ 450 msec for males or ≥ 470 msec for females at Screening NOTE: Protocol Amendment 2.1 eliminates Exclusion Criterion #3.
Pregnant or breast-feeding
History of allergy or sensitivity to study medication (including excipients) or other iminosugars (e.g., miglustat, miglitol)
Subject is treated or has been treated with any investigational drug within 30 days of study start
Subject is currently treated or has ever been treated with AT1001
Any intercurrent condition or concomitant medication use considered to be an absolute contraindication to kidney biopsy or that may preclude accurate interpretation of study data
Otherwise unsuitable for the study, in the opinion of the Investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00925301

Hide Study Locations

Locations

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
University of California School of Medicine
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66150
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Infusion Associates
Grand Rapids, Michigan, United States, 49525
United States, New York
New York Presbyterian/Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45299
United States, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Baylor Research Institute
Dallas, Texas, United States, 75226
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
United States, Virginia
O & O Alpan LLC
Springfield, Virginia, United States, 22152
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Argentina
University of Austral
Buenos Aires, Argentina, B16641NZ
Hospital Britanico
Capital Federal, Argentina, C1280AEB
Australia
Women's and Children's Hospital
Adelaide, Australia, 5600
Royal Melbourne Hospital
Parkville, Australia, 3065
Belgium
Universitair Ziekenhuis Antwerpen, Koningin Paola Kinderziekenhuis
Antwerpen, Belgium, 2020
Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Brazil, 90035-003
Federal University of Sao Paolo
Sao Paulo, Brazil, 04020-041
Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
Sao Paulo, Brazil, 14048-900
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G1X8
Canada, Quebec
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada
Denmark
Rigshospitalet
Kobenhavn, Denmark, 2100
Egypt
Cairo University Hospital - Al Kasr El Ainy
Giza, Egypt, 11451
France
Hôpital Raymond Poincaré
Garches, France
Germany
Universitaetsklinikum Wuerzburg
Wuerzburg, Germany, 97080
Italy
Policlinico Universitario Agostino Gemelli
Roma, Italy, 00168
Netherlands
Academisch Medisch Centrum
Amsterdam, Netherlands, 1105AZ
Poland
Instytut Kardiologii im. Kardynala Sr. Wyszynskiego
Warszawa, Poland, 04-628
South Africa
Morningside Clinic
Johannesburg, South Africa, 2021
Spain
Fundacio Puigvert
Barcelona, Spain, 08025
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
Turkey
Gazi University Hospital
Ankara, Turkey, 06500
United Kingdom
The Royal Free Hospital
London, United Kingdom, NW3 2QG
Hope Hospital, Salford Royal NHS Foundation Trust
Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Amicus Therapeutics

GlaxoSmithKline

Investigators

Study Director:

Medical Monitor, Clinical Research

Amicus Therapeutics

More Information

No publications provided

Responsible Party:	Amicus Therapeutics
ClinicalTrials.gov Identifier:	NCT00925301 History of Changes
Other Study ID Numbers:	AT1001-011
Study First Received:	June 19, 2009
Last Updated:	September 21, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amicus Therapeutics:

Fabry Disease
Fabry
Lysosomal Storage Disorders
LSD
Amicus

Additional relevant MeSH terms:

Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 23, 2013