A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Female 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]).

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.