• Safety and tolerability
  

• Pharmacodynamic parameters
  
• Functional parameters (cardiac, renal, CNS)
  

This study will be a phase 2, open-label trial in previously untreated patients with Fabry disease. The trial will consist of a 4 week screening phase, a 12-week treatment phase that may be extended up to an additional 36 weeks, and a 2-week follow-up phase.

Twelve female patients are planned to be enrolled at two sites. The number of visits for the first part of the study is 7 and for the extension treatment part, a further 3. Once patients have completed treatment, they will be required to attend a follow up visit.

After determination of missense genotype, patients will be initially screened on Day -28 by collection of blood for evaluation of enhanceablity of α-Gal A in leukocytes. Patients will come to the treatment facility for Screening assessments on Day -2 and Day -1, and baseline assessments including α-Gal A and GL-3 in plasma (leukocytes), skin tissue, cardiac tissue, and renal tissue, GL-3 in urine, and baseline evaluation of safety, cardiac, renal, and CNS parameters as described in the schedule of assessments. From Day 1, patients will initiate AT1001 once every other day oral dosing for 12 weeks. Patients will be stratified by α-Gal A enzyme activity (high > 40%, and low ≤ 40%) then randomly assigned to receive one of three specified dose levels.

Patients will return to the treatment facility for Visits 1 through 4. Safety measures will be performed at all visits. Pharmacokinetic (PK) measures will be performed predose and up to 10 hours postdose on Days 1, 14 and 84. Pharmacodynamic measurements in the form of blood leukocyte measurements of α-Gal A and plasma and urine measurements of α-Gal A and GL-3 will be performed at each visit. A final set of skin, cardiac, and renal biopsies will be performed at Visit 4. Evaluations of cardiac and renal function parameters as described in the schedule of assessments will be performed at various timepoints: ECG and serum creatinine for Visits 1 through 4; glomerular filtration rate (GFR); and 24-hr Quantitative Holter monitor ECG, ECHO, cardiac MRI, natriuretic factor, treadmill cardiac stress test, renal ultrasound (to be performed at Porto Alegre site only), Brain MRI, QSART (to be performed at Porto Alegre site only) and transcranial Doppler at Screening and Visit 4. Cognitive Testing will be performed at Screening, Baseline, and Visit 4.

Patients will also come to the treatment facility at the end of the treatment period.

If they are not continuing into the 36-week treatment extension, patients will return to the clinic for a follow-up visit 2 weeks after the end of treatment. Patients continuing into the treatment extension will return to the clinic for additional visits at Weeks 24 (Visit 6), 36 (Visit 7) and 48 (Visit 8) for safety assessments and specific pharmacodynamic and functional measurements.