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

NCT ID: NCT04990388

Last Updated: 2024-04-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-18

Study Completion Date

2023-03-20

Brief Summary

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

Detailed Description

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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).

Conditions

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Glycogen Storage Disease Type III

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The SAD and OL-RD cohorts will be open-label, while the DB-RD dose cohorts will be randomized, double-blind, and placebo-controlled.

Study Groups

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UX053 Dose Level 1S ->OL-1R

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.

Group Type EXPERIMENTAL

UX053

Intervention Type BIOLOGICAL

mRNA-based biologic

Antipyretic

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H2 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H1 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

UX053 Dose Level 2S->OL-2R

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.

Group Type EXPERIMENTAL

UX053

Intervention Type BIOLOGICAL

mRNA-based biologic

Antipyretic

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H2 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H1 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

UX053 Dose Level 3S->OL-3R

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.

Group Type EXPERIMENTAL

UX053

Intervention Type BIOLOGICAL

mRNA-based biologic

Antipyretic

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H2 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H1 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

UX053 or Placebo Dose Level DB-1R

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.

Group Type EXPERIMENTAL

UX053

Intervention Type BIOLOGICAL

mRNA-based biologic

Placebo

Intervention Type OTHER

consists of the same components as the formulation buffer for UX053

Antipyretic

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H2 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H1 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

UX053 Dose Level DB-2R

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.

Group Type EXPERIMENTAL

UX053

Intervention Type BIOLOGICAL

mRNA-based biologic

Placebo

Intervention Type OTHER

consists of the same components as the formulation buffer for UX053

Antipyretic

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H2 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H1 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

UX053 Dose Level DB-3R

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.

Group Type EXPERIMENTAL

UX053

Intervention Type BIOLOGICAL

mRNA-based biologic

Placebo

Intervention Type OTHER

consists of the same components as the formulation buffer for UX053

Antipyretic

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H2 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

H1 Blocker

Intervention Type DRUG

participants will receive oral premedication prior to infusion

Interventions

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UX053

mRNA-based biologic

Intervention Type BIOLOGICAL

Placebo

consists of the same components as the formulation buffer for UX053

Intervention Type OTHER

Antipyretic

participants will receive oral premedication prior to infusion

Intervention Type DRUG

H2 Blocker

participants will receive oral premedication prior to infusion

Intervention Type DRUG

H1 Blocker

participants will receive oral premedication prior to infusion

Intervention Type DRUG

Other Intervention Names

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paracetamol acetaminophen ibuprofen famotidine cetirizine

Eligibility Criteria

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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


* 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

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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

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University of California, Irvine

Orange, California, United States

Site Status

Rare Disease Research

Atlanta, Georgia, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Texas, Health Science Center of Houston

Houston, Texas, United States

Site Status

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Countries

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United States Italy Spain

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://ultrarareadvocacy.com/glycogen-storage-disease-type-iii-gsdiii/

Ultragenyx Patient Advocacy/GSD III Disease Information

Other Identifiers

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2021-000903-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UX053-CL101

Identifier Type: -

Identifier Source: org_study_id

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