Safety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III)

A Phase 1/2 First-in-human, Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses and Repeat Doses of UX053 in Patients With GSD III

The primary objective of the study is to evaluate the safety of UX053 in adults with Glycogen Storage Disease Type III (GSD III).

This study is a phase 1/2 first-in-human (FIH), study to evaluate the safety, tolerability, and pharmacokinetic (PK) of a single ascending dose (SAD) and repeat doses (RD) of UX053 in patients with GSD III. The SAD cohorts will be open-label (OL). There will be two types of RD cohorts, an open-label (OL-RD) and a randomized, double-blind (DB), and placebo-controlled (DB-RD).

Key Inclusion Criteria:

• Confirmed diagnosis of GSD III by gene sequencing or enzymatic testing
• Alanine aminotransferase at or below 5 times normal during the three months prior to dosing
• Willing and able to comply with standard dietary management of GSD III

Inclusion Criteria for Participants Rescreening Into OL-RD Cohorts After Treatment with UX053 in SAD Cohort:

• If a significant rise in ALT occurs after the prior dose, ALT should show a decreasing trend toward the subject's baseline value
• Total bilirubin, platelets and international normalized ratio (INR) is within normal limits

Key Exclusion Criteria:

• History of liver transplant or currently awaiting liver transplant
• History of cirrhosis
• Active Hepatitis B or C
• Severe kidney impairment
• History of liver cancer or large liver tumors
• History of any cancer within the past 3 years
• Known history of HIV infection
• Known severe allergy to polyethylene glycol (PEG), polysorbate, or mRNA vaccine
• Heart failure that causes marked limitation in physical activity
• Poorly controlled diabetes
• Poorly controlled hypothyroidism
• Treatment with immunosuppressive medications such as those used to treat chronic autoimmune conditions and solid organ transplants
• Pregnant or nursing, or planning to become pregnant during the study

Exclusion Criteria for Participants Rescreening Into OL-RD Cohorts After Treatment with UX053 in SAD Cohort:

• New or worsening symptoms of liver disease (including new or worsening hepatomegaly) along with any increase in transaminase levels
• Receipt of any blood product administration (eg, packed red blood cells, platelet, FFP) for management of consumptive coagulopathy
• An ALT level that is ≥ 8x ULN and > 2x the participants baseline value in the absence of an alternative explanation

Note: Additional inclusion/exclusion criteria may apply, per protocol