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

NCT04990388 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: UX053-CL1012021-000903-19
• Study Type: interventional
• Target: 9
• Locations: 3 countries
• Sites: 6

Brief Summary

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

Conditions

Glycogen Storage Disease Type III

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Pharmacokinetics (PK) of Amylo-α-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

• 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

• 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

• 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

• 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

Study Arms (6)

UX053 Dose Level 1S ->OL-1R

EXPERIMENTAL

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.

Biological: UX053; Drug: Antipyretic; Drug: H2 Blocker; Drug: H1 Blocker

UX053 Dose Level 2S->OL-2R

EXPERIMENTAL

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.

Biological: UX053; Drug: Antipyretic; Drug: H2 Blocker; Drug: H1 Blocker

UX053 Dose Level 3S->OL-3R

EXPERIMENTAL

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.

Biological: UX053; Drug: Antipyretic; Drug: H2 Blocker; Drug: H1 Blocker

UX053 or Placebo Dose Level DB-1R

EXPERIMENTAL

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.

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

UX053 Dose Level DB-2R

EXPERIMENTAL

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.

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

UX053 Dose Level DB-3R

EXPERIMENTAL

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.

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

Interventions

UX053 BIOLOGICAL

mRNA-based biologic

UX053 Dose Level 1S ->OL-1R; UX053 Dose Level 2S->OL-2R; UX053 Dose Level 3S->OL-3R; UX053 Dose Level DB-2R; UX053 Dose Level DB-3R; UX053 or Placebo Dose Level DB-1R

Placebo OTHER

consists of the same components as the formulation buffer for UX053

UX053 Dose Level DB-2R; UX053 Dose Level DB-3R; UX053 or Placebo Dose Level DB-1R

Antipyretic DRUG

participants will receive oral premedication prior to infusion

Also known as: paracetamol, acetaminophen, ibuprofen

UX053 Dose Level 1S ->OL-1R; UX053 Dose Level 2S->OL-2R; UX053 Dose Level 3S->OL-3R; UX053 Dose Level DB-2R; UX053 Dose Level DB-3R; UX053 or Placebo Dose Level DB-1R

H2 Blocker DRUG

participants will receive oral premedication prior to infusion

Also known as: famotidine

UX053 Dose Level 1S ->OL-1R; UX053 Dose Level 2S->OL-2R; UX053 Dose Level 3S->OL-3R; UX053 Dose Level DB-2R; UX053 Dose Level DB-3R; UX053 or Placebo Dose Level DB-1R

H1 Blocker DRUG

participants will receive oral premedication prior to infusion

Also known as: cetirizine

UX053 Dose Level 1S ->OL-1R; UX053 Dose Level 2S->OL-2R; UX053 Dose Level 3S->OL-3R; UX053 Dose Level DB-2R; UX053 Dose Level DB-3R; UX053 or Placebo Dose Level DB-1R

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (6)

University of California, Irvine

Orange, California, 92868, United States

Location

Rare Disease Research

Atlanta, Georgia, 30329, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas, Health Science Center of Houston

Houston, Texas, 77030, United States

Location

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Related Links

• Ultragenyx Patient Advocacy/GSD III Disease Information

MeSH Terms

Conditions

Glycogen Storage Disease Type III

Interventions

Antipyretics; Acetaminophen; Ibuprofen; Histamine H2 Antagonists; Famotidine; Histamine Antagonists; Cetirizine

Condition Hierarchy (Ancestors)

Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxyzine; Piperazines

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8567

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The SAD and OL-RD cohorts will be open-label, while the DB-RD dose cohorts will be randomized, double-blind, and placebo-controlled.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 4, 2021
• Study Start: October 18, 2021
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: April 16, 2024
• Results First Posted: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); ES (1); US (4)