Clinical trial NCT00283959: A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Official title: A Phase 2, Open-Label, Single Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fabry Disease
Keywords: Amicus Therapeutics
AT1001
Galafold
Migalastat
Substrate
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-01-31
Enrollment: 4
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) and how migalastat works in participants with Fabry disease.

Detailed description: 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' genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat via an in vitro assay. 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 150 milligrams (mg) once every other day (QOD) for 12 weeks during the treatment period. Participants could then opt to participate in the extension period.

Eligibility criteria: Inclusion Criteria:

* Males between 18 and 65 years of age (inclusive)
* Hemizygous 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
* Had documented evidence of cardiac and/or renal dysfunction (for example, abnormal electrocardiogram (ECG), left ventricular hypertrophy, renal insufficiency) and/or cerebral tissue dysfunction documented by evidence of stroke and/or peripheral nervous tissue dysfunction (for example, intolerance to heat/cold, decrease of perspiration)
* Must have been previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease or were able to stop ERT for at least 18 weeks or up to three months, and be willing to undergo two kidney and three skin biopsies
* Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study
* Were willing and able to sign an informed consent form

Exclusion Criteria:

* History of significant disease other than Fabry disease
* History of organ transplant
* Serum creatinine \>2 mg per deciliter on Day -2
* Screening 12-lead ECG demonstrating corrected QT interval \>450 milliseconds prior to dosing
* Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
* Took any of the following prohibited medications: 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

Primary outcomes:
measure: Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 (after dosing) through Week 48 (end of extension period)
Secondary outcomes:
measure: α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
timeFrame: Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
Other outcomes:
Locations:
city: Parkville
country: Australia
city: Porto Alegre
country: Brazil
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor, Clinical Research
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.