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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04990388
Recruitment Status : Recruiting
First Posted : August 4, 2021
Last Update Posted : May 27, 2022
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

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).

Condition or disease Intervention/treatment Phase
Glycogen Storage Disease Type III Biological: UX053 Other: Placebo Drug: Antipyretic Drug: H2 Blocker Drug: H1 Blocker Phase 1 Phase 2

Detailed Description:
This study is a phase 1/2 first-in-human (FIH), 2-part study to evaluate the safety, tolerability, and pharmacokinetic (PK) of a single ascending dose (SAD; part 1) and repeat doses (RD; part 2) of UX053 in patients with GSD III. Single SAD and RD of UX053 are tested in separate cohorts. The SAD cohorts will be open-label, while the RD dose cohorts will be randomized, double-blind, and placebo-controlled.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The SAD cohorts will be open-label, while the RD dose cohorts will be randomized, double-blind, and placebo-controlled.
Primary Purpose: Treatment
Official Title: A Phase 1/2 First-in-human, 2-part Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (Part 1: Open-label) and Repeat Doses (Part 2: Randomized, Double-blind, Placebo-controlled) of UX053 in Patients With GSD III
Actual Study Start Date : October 18, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023


Arm Intervention/treatment
Experimental: Stage 1: UX053 Dose Level 1S
Participants to receive a single, peripheral intravenous (IV) infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 1: UX053 Dose Level 2S
Participants to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 1: UX053 Dose Level 3S
Participants to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 1: UX053 Dose Level 4S
Participants to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 2: UX053 Dose Level 1R
Participants randomized to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker every 2 weeks (Q2W) for 5 doses.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 2: UX053 Dose Level 2R
Participants randomized to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker Q2W for 5 doses.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 2: UX053 Dose Level 3R
Participants randomized to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker Q2W for 5 doses.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Experimental: Stage 2: UX053 Dose Level 4R
Participants randomized to receive a single, peripheral IV infusion of UX053 plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker Q2W for 5 doses.
Biological: UX053
mRNA-based biologic

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine

Placebo Comparator: Stage 2: Placebo Dose
Participants randomized to receive a single, peripheral IV infusions of matching placebo, plus premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker Q2W for 5 doses.
Other: Placebo
consists of the same components as the formulation buffer for UX053

Drug: Antipyretic
participants will receive oral premedication prior to infusion
Other Names:
  • paracetamol
  • acetaminophen
  • ibuprofen

Drug: H2 Blocker
participants will receive oral premedication prior to infusion
Other Name: famotidine

Drug: H1 Blocker
participants will receive oral premedication prior to infusion
Other Name: cetirizine




Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (TEAEs), serious TEAEs, and related TEAEs in the SAD and RD Periods [ Time Frame: 48 weeks ]

Secondary Outcome Measures :
  1. PK parameters of AGL mRNA: time of maximum observed concentration (Tmax) [ Time Frame: From pre-infusion up to Day 28 ]
  2. PK parameters of AGL mRNA: maximum concentration (Cmax) [ Time Frame: From pre-infusion up to Day 28 ]
  3. PK parameters of AGL mRNA: area under the concentration-time curve (AUC) from time 0 to the last measurable concentration (AUClast) [ Time Frame: From pre-infusion up to Day 28 ]
  4. PK parameters of AGL mRNA: AUC from time 0 to infinity (AUCinf) [ Time Frame: From pre-infusion up to Day 28 ]
  5. PK parameters of AGL mRNA: AUC from time 0 to end of dosing period (AUCtau; RD Period only) [ Time Frame: From pre-infusion up to Day 28 ]
  6. PK parameters of AGL mRNA: accumulation ratio (calculated as AUC after repeat dose / AUC after a single dose; RAUC; RD Period only) [ Time Frame: From pre-infusion up to Day 28 ]
  7. PK parameters of AGL mRNA: time of last measurable concentration (Tlast) [ Time Frame: From pre-infusion up to Day 28 ]
  8. PK parameters of AGL mRNA: half life (T1/2) [ Time Frame: From pre-infusion up to Day 28 ]
  9. PK parameters of AGL mRNA: clearance (CL) [ Time Frame: From pre-infusion up to Day 28 ]
  10. PK parameters of AGL mRNA: volume of distribution in a steady state (Vss; SAD Period only) [ Time Frame: From pre-infusion up to Day 28 ]
  11. PK parameters of ATX95: Tmax [ Time Frame: From pre-infusion up to Day 28 ]
  12. PK parameters of ATX95: Cmax [ Time Frame: From pre-infusion up to Day 28 ]
  13. PK parameters of ATX95: AUClast [ Time Frame: From pre-infusion up to Day 28 ]
  14. PK parameters of ATX95: AUCinf [ Time Frame: From pre-infusion up to Day 28 ]
  15. PK parameters of ATX95: AUCtau; RD Period only [ Time Frame: From pre-infusion up to Day 28 ]
  16. PK parameters of ATX95: accumulation ratio (calculated as AUC after repeat dose / AUC after a single dose; RAUC; RD Period only) [ Time Frame: From pre-infusion up to Day 28 ]
  17. PK parameters of ATX95: Tlast [ Time Frame: From pre-infusion up to Day 28 ]
  18. PK parameters of ATX95: T1/2 [ Time Frame: From pre-infusion up to Day 28 ]
  19. PK parameters of ATX95: CL [ Time Frame: From pre-infusion up to Day 28 ]
  20. PK parameters of ATX95: Vss; SAD Period only [ Time Frame: From pre-infusion up to Day 28 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04990388


Contacts
Layout table for location contacts
Contact: Patients Contact: Trial Recruitment 1-888-756-8657 trialrecruitment@ultragenyx.com
Contact: HCPs Contact: Medical Information 1-888-756-8657 medinfo@ultragenyx.com

Locations
Layout table for location information
United States, California
University of California, Irvine Recruiting
Orange, California, United States, 92868
United States, Georgia
Rare Disease Research Not yet recruiting
Atlanta, Georgia, United States, 30329
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas, Health Science Center of Houston Recruiting
Houston, Texas, United States, 77030
Canada, Ontario
The Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1Y4E9
France
Hopital Femme Mere Enfant Not yet recruiting
Bron, Cedex, France, 69677
Institut de Myologie - Hopital Antoine Béclère Not yet recruiting
Clamart, France, 92140
Italy
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Recruiting
Milan, Italy, 20122
Spain
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
United Kingdom
Salford Royal NHS Foundation Trust Not yet recruiting
Salford, Greater Manchester, United Kingdom, M68HD
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
Layout table for investigator information
Study Director: Medical Director, MD, PhD Ultragenyx Pharmaceutical Inc
Additional Information:
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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT04990388    
Other Study ID Numbers: UX053-CL101
2021-000903-19 ( EudraCT Number )
First Posted: August 4, 2021    Key Record Dates
Last Update Posted: May 27, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glycogen Storage Disease
Glycogen Storage Disease Type III
Metabolic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Acetaminophen
Antipyretics
Cetirizine
Ibuprofen
Famotidine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Ulcer Agents
Gastrointestinal Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Anti-Allergic Agents
Histamine H1 Antagonists, Non-Sedating