Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease

• urine GL-3 levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• renal function (assessed by iohexol GFR, eGFR, and 24-hour urine protein) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• safety and tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

The purpose of this study is to compare the effect of AT1001 (migalastat hydrochloride) versus placebo on kidney GL-3.

This double-blind, randomized, placebo-controlled study will be conducted in 60 patients at approximately 40 sites worldwide. The study will consist of two stages and an open-label treatment extension phase:

Stage 1 includes a screening period of up to 2 months followed by a 6-month treatment period which will involve 4 visits to the clinic. Patients will be randomized in equal proportions to receive either AT1001 or placebo.

After completing the 6-month double-blind phase, all patients will enter Stage 2 of the study and receive AT1001 in an open-label manner. Stage 2 treatment will last for 6 months and will involve 4 visits to the clinic.

Subjects who complete both Stage 1 and Stage 2 of the study as scheduled may be offered the opportunity to participate in a an open-label treatment extension phase with AT1001. The open-label treatment extension phase will last 13 months and will involve 3 visits to the clinic.

Study assessments will include clinical laboratory tests, 12-lead ECG, kidney biopsy, kidney function testing, echocardiography, and patient reported outcomes.

• Drug: migalastat hydrochloride
  oral capsule every other day
  Other Name: AT1001
• Drug: Placebo
  oral capsule every other day
  Other Name: Placebo

• Experimental: AT1001 Oral Capsule
  AT1001
  Intervention: Drug: migalastat hydrochloride
• Placebo Comparator: Placebo Oral Capsule
  Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

1. Male or female between the ages of 16 and 74 diagnosed with Fabry disease
2. Confirmed GLA mutation that has been shown to be responsive to AT1001 in vitro
3. Subject has never been treated with ERT or has not received ERT for 6 consecutive months or longer before the screening visit for the study
4. Urine GL-3 greater than or equal to four times the upper limit of normal at Screening
5. Subjects taking angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) must be on a stable dose for a minimum of 4 weeks before the baseline visit
6. Women who can become pregnant and all men agree to be sexually abstinent or use medically accepted methods of birth control during the study and for 30 days after study completion
7. Subject is willing and able to provide written informed consent, and assent if applicable

Exclusion Criteria:

1. Subject has undergone or is scheduled to undergo kidney transplantation, or is currently on dialysis
2. eGFR < 30 mL/min/1.73m2 (CKD Stage 4 or 5) based on MDRD equation
3. QTc ≥ 450 msec for males or ≥ 470 msec for females at Screening NOTE: Protocol Amendment 2.1 eliminates Exclusion Criterion #3.
4. Pregnant or breast-feeding
5. History of allergy or sensitivity to study medication (including excipients) or other iminosugars (e.g., miglustat, miglitol)
6. Subject is treated or has been treated with any investigational drug within 30 days of study start
7. Subject is currently treated or has ever been treated with AT1001
8. Any intercurrent condition or concomitant medication use considered to be an absolute contraindication to kidney biopsy or that may preclude accurate interpretation of study data
9. Otherwise unsuitable for the study, in the opinion of the Investigator