A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Female Participants With Fabry Disease

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 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 \[mg\]).

Eligibility Criteria:
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.