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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00925301




Registration number
NCT00925301
Ethics application status
Date submitted
19/06/2009
Date registered
19/06/2009
Date last updated
1/10/2018

Titles & IDs
Public title
Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease
Scientific 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
Secondary ID [1] 0 0
FACETS
Secondary ID [2] 0 0
AT1001-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - migalastat hydrochloride
Treatment: Drugs - Placebo

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.

Placebo Comparator: Placebo - Placebo capsule taken orally QOD for 6 months.


Treatment: Drugs: migalastat hydrochloride
Oral capsule QOD

Treatment: Drugs: Placebo
Oral capsule QOD

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Month 6
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Month 6
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, Months 6, 12, and 24

Eligibility
Key inclusion criteria
- Male or female between the ages of 16 and 74 diagnosed with Fabry disease.

- Confirmed mutant form of a-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.
Minimum age
16 Years
Maximum age
74 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
5006 - Adelaide
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Brazil
State/province [14] 0 0
Porto Alegre
Country [15] 0 0
Brazil
State/province [15] 0 0
Sao Paulo
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Denmark
State/province [17] 0 0
Kobenhavn
Country [18] 0 0
Egypt
State/province [18] 0 0
Cairo
Country [19] 0 0
France
State/province [19] 0 0
Garches
Country [20] 0 0
Italy
State/province [20] 0 0
Roma
Country [21] 0 0
Poland
State/province [21] 0 0
Warszawa
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Zaragoza
Country [24] 0 0
Turkey
State/province [24] 0 0
Ankara
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amicus Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT00925301
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor, Clinical Research
Address 0 0
Amicus Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications