- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00304512
A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Female Participants With Fabry Disease
October 1, 2018 updated by: Amicus Therapeutics
A Phase 2, Open-Label, Multiple Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Female Patients With Fabry Disease
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Study Overview
Detailed Description
This was a Phase 2, open-label study in female participants with Fabry disease.
The study consisted of a 4-week screening period, during which participants' galactosidase (GLA) genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat.
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 once every other day (QOD) for 12 weeks during the treatment period and the optional 36-week extension period for a total treatment duration of up to 48 weeks.
Participants were stratified by α-Gal A enzyme activity (high >40%, and low ≤40%) then randomly assigned to receive migalastat at 1 of 3 specified dose levels (50, 150, or 250 milligrams [mg]).
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Victoria
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Parkville, Victoria, Australia, 3050
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Porto Alegre, Brazil, RS, 90035-903
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Montréal, Canada, H4J 1C5
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Paris, France, 75015
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Salford, United Kingdom, M6 8HD
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Georgia
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Decatur, Georgia, United States, 30033
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Females between 18 and 65 years of age (inclusive)
- Heterozygous 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
- Were naïve to enzyme replacement therapy (ERT) and other therapies, except for palliative therapies for the signs and symptoms of Fabry disease, or stopped ERT for at least 18 weeks
- Had end organ dysfunction, even minimal, demonstrated by abnormal electrocardiogram (ECG) or evidence of left ventricular hypertrophy documented by echocardiogram or by cardiac biopsy; or renal insufficiency documented by common clinical assessments such as creatinine and glomerular filtration rate or by renal biopsy; or brain tissue dysfunction as documented by evidence of stroke (clinically or imaging); or peripheral nervous tissue dysfunction documented by complaints of intolerance to heat or cold, decreased vibratory sense and proprioception, decreased ability to perspire, or acroparesthesia.
- Were willing to undergo 2 renal and 3 skin biopsies
- Agreed to be sexually abstinent or practice an effective method of contraception when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study for women of childbearing potential.
- Were willing and able to provide written informed consent
Exclusion Criteria:
- Pregnant or lactating
- History of organ transplant
- History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study)
- Serum creatinine >176 micromoles/liter on Day -2
- Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds
- Pacemaker or other contraindication for magnetic resonance imaging scanning
- Taking a medication prohibited by the protocol: 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Migalastat Low Dose 50 mg
Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
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Other Names:
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Experimental: Migalastat Middle Dose 150 mg
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
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Other Names:
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Experimental: Migalastat High Dose 250 mg
Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Time Frame: Day 1 (after dosing) through Week 48
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TEAEs were defined as any adverse event with 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.
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Day 1 (after dosing) through Week 48
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
Time Frame: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)
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The AUC to the last measurable concentration (AUC0-t) was evaluated in plasma following a single oral dose of migalastat on Day 1 and following multiple oral doses on Day 14 (2 weeks) and Day 84 (12 weeks).
All samples were collected on each dosing day.
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0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)
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α-Gal A Activity In Leukocytes At Baseline, Week 12, And Week 48
Time Frame: Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
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Leukocytes were isolated from whole blood and lysed, and α-Gal A activity was measured using 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/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 leukocytes are presented by individual participants.
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Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- Giugliani R, Waldek S, Germain DP, Nicholls K, Bichet DG, Simosky JK, Bragat AC, Castelli JP, Benjamin ER, Boudes PF. A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects. Mol Genet Metab. 2013 May;109(1):86-92. doi: 10.1016/j.ymgme.2013.01.009. Epub 2013 Jan 26.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 7, 2006
Primary Completion (Actual)
May 9, 2008
Study Completion (Actual)
May 9, 2008
Study Registration Dates
First Submitted
March 17, 2006
First Submitted That Met QC Criteria
March 17, 2006
First Posted (Estimate)
March 20, 2006
Study Record Updates
Last Update Posted (Actual)
October 3, 2018
Last Update Submitted That Met QC Criteria
October 1, 2018
Last Verified
October 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Cerebral Small Vessel Diseases
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Fabry Disease
Other Study ID Numbers
- FAB-CL-204
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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