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

Ultragenyx

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Glycogen Storage Disease Type III

Treatments: Biological: UX053; Other: Placebo; Drug: Antipyretic; Drug: H2 Blocker; Drug: H1 Blocker

Study type: Interventional

Funder types: Industry

Identifiers

NCT04990388

UX053-CL101

2021-000903-19 (EudraCT Number)

Details and patient eligibility

About

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

Full 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).

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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9 participants in 6 patient groups

UX053 Dose Level 1S ->OL-1R

Experimental group

Description:

Participants receive a single, peripheral intravenous (IV) infusion of UX053. After completion of the 90-day Follow up Period, participants can enter the open label repeat dose (OL-RD) cohort where they will receive UX053 every 4 weeks (Q4W) for 4 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.

Treatment:

Biological: UX053

Drug: H1 Blocker

Drug: H2 Blocker

Drug: Antipyretic

UX053 Dose Level 2S->OL-2R

Experimental group

Description:

Participants receive a single, peripheral intravenous (IV) infusion of UX053. After completion of the 90-day Follow up Period, participants can enter the open label repeat dose (OL-RD) cohort where they will receive UX053 every 4 weeks (Q4W) for 4 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.

Treatment:

Biological: UX053

Drug: H1 Blocker

Drug: H2 Blocker

Drug: Antipyretic

UX053 Dose Level 3S->OL-3R

Experimental group

Description:

Participants receive a single, peripheral intravenous (IV) infusion of UX053. After completion of the 90-day Follow up Period, participants can enter the open label repeat dose (OL-RD) cohort where they will receive UX053 every 4 weeks (Q4W) for 4 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.

Treatment:

Biological: UX053

Drug: H1 Blocker

Drug: H2 Blocker

Drug: Antipyretic

UX053 or Placebo Dose Level DB-1R

Experimental group

Description:

Participants randomized to receive a single, peripheral IV infusion of UX053 or Placebo every 2 weeks (Q2W) for 5 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.

Treatment:

Other: Placebo

Biological: UX053

Drug: H1 Blocker

Drug: H2 Blocker

Drug: Antipyretic

UX053 Dose Level DB-2R

Experimental group

Description:

Participants randomized to receive a single, peripheral IV infusion of UX053 or Placebo every 2 weeks (Q2W) for 5 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.

Treatment:

Other: Placebo

Biological: UX053

Drug: H1 Blocker

Drug: H2 Blocker

Drug: Antipyretic

UX053 Dose Level DB-3R

Experimental group

Description:

Participants randomized to receive a single, peripheral IV infusion of UX053 or Placebo every 2 weeks (Q2W) for 5 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.

Treatment:

Other: Placebo

Biological: UX053

Drug: H1 Blocker

Drug: H2 Blocker

Drug: Antipyretic