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

Glycogen Storage Disease Type III Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04990388
• Other study ID #: UX053-CL101
• Secondary ID: 2021-000903-19
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 18, 2021
• Est. completion date: March 20, 2023

Study information

• Verified date: April 2024
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 20, 2023
• Est. primary completion date: March 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disease
• Glycogen Storage Disease
• Glycogen Storage Disease Type III

Intervention

Biological:
• UX053
mRNA-based biologic

Other:
• Placebo
consists of the same components as the formulation buffer for UX053

Drug:
• Antipyretic
participants will receive oral premedication prior to infusion
• H2 Blocker
participants will receive oral premedication prior to infusion
• H1 Blocker
participants will receive oral premedication prior to infusion

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico	Milan
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Rare Disease Research	Atlanta	Georgia
United States	University of Texas, Health Science Center of Houston	Houston	Texas
United States	University of California, Irvine	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

United States,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes	An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE is defined as any AE not present prior to the initiation of the drug treatment or any AE already present that worsens in either intensity or frequency following exposure to the drug treatment. An SAE is an AE that meets any of the following criteria in the view of either the Investigator or Ultragenyx: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; disability/Incapacity; congenital anomaly/birth defect not present at screening; other important medical events. Severity of events were graded as mild (grade1), moderate (grade 2), severe (grade 3), life-threatening (grade 4), or death (grade 5).	From first dose of study drug through the end of study (up to Day 90)
Secondary	Pharmacokinetics (PK) of Amylo-a-1,6-glucosidase 4-alpha-glucanotransferase Messenger Ribonucleic Acid (AGL mRNA) and the Excipient ATX95: Maximum Blood/Plasma Concentration (Cmax)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion
Secondary	PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion
Secondary	PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion
Secondary	PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion
Secondary	PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion
Secondary	PK of AGL mRNA and the Excipient ATX95: Clearance (CL)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion
Secondary	PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss)		Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion

External Links

•   Ultragenyx Patient Advocacy/GSD III Disease Information