Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease

This was a Phase 3, randomized, open-label, active-controlled study to evaluate the efficacy and safety of 150 milligrams (mg) of migalastat hydrochloride (migalastat) (equivalent to 123 mg of migalastat) once every other day (QOD) and ERT in male and female participants with Fabry disease who were receiving ERT and who have an α Gal-A mutation that is amenable to migalastat, based on the clinical trial HEK assay. This was a 2-part study. Part 1, the 18-month randomized phase, evaluated participants who received either migalastat 150 mg QOD or ERT per prescribing physicians' instructions for efficacy and safety. Part 2, the optional 12-month open-label extension (OLE) phase in which all participants received migalastat, also explored efficacy and safety. For Part 2, all participants who received ERT in Part 1 were given migalastat. Data presented in this posting include efficacy data from the 18-month randomized period and safety data from the entire study (18-month randomized period and 12-month optional OLE [total of 30 months]).

Inclusion criteria

• Male or female between the ages of 16 and 74 diagnosed with Fabry disease
• Confirmed α Gal-A mutation that is amenable to migalastat, based on the clinical trial HEK assay
• Participant has been on ERT for at least 12 months before screening/baseline
• Dose level and regimen of ERT have been stable for 3 months before screening/baseline and is at least 80% of the currently labeled dose and regimen for this time period
• Glomerular filtration rate (GFR) ≥ 30 milliliter (mL)/minute (min) /1.73 m^2
• Participants taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be on a stable dose for at least 4 weeks before screening/baseline
• Women who can become pregnant and all men agree to be sexually abstinent or use medically accepted methods of birth control throughout the duration of the study and for up to 30 days after last dose of study medication
• Participant is willing and able to provide written informed consent and assent if applicable

Exclusion criteria

• Participant has undergone, or is scheduled to undergo, kidney transplantation or any other solid organ transplantation
• Participant is on regular dialysis that is specifically for the treatment of chronic kidney disease
• Participant has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before screening/baseline
• Participant has clinically significant unstable cardiac disease in the opinion of the investigator (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association (NYHA) class III or IV congestive heart failure)
• Pregnant or breast-feeding
• History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol)
• Participant has absolute contraindication to iohexol and/or inability to undergo iohexol GFR testing
• Participant requires treatment with Glyset® (miglitol), or Zavesca® (miglustat)
• Participant received any investigational/experimental drug, biologic or device within 30 days of screening/baseline
• Any intercurrent illness or condition that may preclude the participant from fulfilling the study requirements or suggests to the investigator that the participant may have an unacceptable risk by participating in this study