A Phase II, Open-label Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy in Males With Classic Fabry Disease Who Have Never Received Any Treatment
This is a Phase II, open-label study designed to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of AL01211 in male subjects with classic Fabry disease who have never received any treatment (eg. ERT or chaperone therapy). Eligible subjects will receive 182 days (26 weeks) of study treatment as the primary study period followed by an extension period. The total study duration for a subject is up to at most 2 years including the primary period of 26 weeks.
• Male subjects with classic Fabry mutations with between 18 and 60 years of age, inclusive, at screening.
• Have never received any Fabry disease-specific treatment (eg. ERT, chaperone therapy).
• Signed and dated informed consent prior to any study mandated procedure.
• Confirmed diagnosis of Fabry disease as documented by the presence of a Fabry genetic variant of known significance and documented (within 10 years prior to study entry) leukocyte αGAL activity of \<4 nmol/hr/mg or plasma αGAL activity of \<1.5 nmol/hr/mL. If the genetic variant is not known or available, genetic test will be done to document the genetic variation after obtaining the patient's informed consent. If documented leukocyte or plasma αGAL activity is unavailable, the subject must consent to plasma αGAL activity screening.
• eGFR ≥50 mL/min/1.73 m2 by CKD-EPI Creatinine-Cystatin Equation (2021) at the screening visit.
• Subject agrees to comply with all procedural requirements as presented in the protocol, including participation in observational period which extends beyond the planned 52-week treatment duration of the study and 1 month follow-up visit.
• For subjects receiving renin-angiotensin-aldosterone system (RAAS) inhibitors/blockers (ACEIs, ARBs, aldosterone receptor antagonists) or sodium-glucose cotransporter-2 (SGLT2) inhibitors, the dose should be stable (ie, prescribed dose and frequency) for at least the immediate 3 months prior to screening.
• Symptom or clinical finding of ≥1 of the characteristic features of Fabry disease, such as, but not limited to, neuropathic pain, symptoms of gastrointestinal, renal, or cardiac dysfunction.
• Willing to undergo opthalmological examination with photodocumentation at baseline and at specified times during the study.
• Plasma Lyso GL3 ≥25 ng/mL.