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Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
This was a Phase 2, open-label study in male 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 24-week treatment period, followed by an optional 24-week extension period. Participants received migalastat once every other day (QOD) for 24 weeks during the treatment period and the optional 24-week extension for a total treatment duration of up to 48 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Migalastat | Experimental | Migalastat 150 milligrams (mg) was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| migalastat HCl | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | 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. | Day 1 (after dosing) through Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48 | PBMC 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/hour [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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor, Clinical Research | Amicus Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Paris | 75015 | France | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27657681 | Derived | 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. | |
| 23176611 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Migalastat | Migalastat 150 milligrams (mg) was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period |
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| Extension Period |
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Safety Population: All participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Migalastat | Migalastat 150 mg was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | 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. | Safety Population: All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Day 1 (after dosing) through Week 48 |
|
Day 1 after dosing through Week 48 (end of extension period)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Migalastat | Migalastat 150 mg was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular tachycardia | Cardiac disorders | MedDRA 8.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Medical Affairs | +1-877-426-4287 (877-4-AMICUS) | MedInfoUSA@amicusrx.com |
| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
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| ID | Term |
|---|---|
| C090092 | migalastat |
| C525167 | larazotide acetate |
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| Baseline, Week 24 (end of treatment period), Week 48 (end of extension period) |
| London |
| NW3 2QG |
| United Kingdom |
| Derived |
| Germain DP, Giugliani R, Hughes DA, Mehta A, Nicholls K, Barisoni L, Jennette CJ, Bragat A, Castelli J, Sitaraman S, Lockhart DJ, Boudes PF. Safety and pharmacodynamic effects of a pharmacological chaperone on alpha-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies. Orphanet J Rare Dis. 2012 Nov 24;7:91. doi: 10.1186/1750-1172-7-91. |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
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| Secondary | α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48 | PBMC 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/hour [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. | PD Population: All participants who received at least 1 dose of study drug and had at least 1 non-missing postbaseline PD parameter recorded. | Posted | Number | nmol 4-MU/hr/mg protein | Baseline, Week 24 (end of treatment period), Week 48 (end of extension period) |
|
|
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| 0 |
| 5 |
| 5 |
| 5 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 8.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 8.0 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 8.0 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA 8.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 8.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 8.0 | Systematic Assessment |
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| Scrotal mass | Reproductive system and breast disorders | MedDRA 8.0 | Systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 8.0 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 8.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 8.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 8.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 8.0 | Systematic Assessment |
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The investigator can only publish the results from this trial provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review. If requested, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
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| Participant 1: Week 48 |
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| Participant 2: Baseline |
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| Participant 2: Week 24 |
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| Participant 2: Week 48 |
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| Participant 3: Baseline |
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| Participant 3: Week 24 |
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| Participant 3: Week 48 |
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| Participant 4: Baseline |
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| Participant 4: Week 24 |
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| Participant 4: Week 48 |
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| Participant 5: Baseline |
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| Participant 5: Week 24 |
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| Participant 5: Week 48 |
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