Safety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III)
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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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04990388 |
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Recruitment Status :
Terminated
(Sponsor decision not related to safety concerns)
First Posted : August 4, 2021
Last Update Posted : April 4, 2023
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Sponsor:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
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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 |
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).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 8 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | The SAD and OL-RD cohorts will be open-label, while the DB-RD dose cohorts will be randomized, double-blind, and placebo-controlled. |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | October 18, 2021 |
| Actual Primary Completion Date : | March 20, 2023 |
| Actual Study Completion Date : | March 20, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 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.
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Biological: UX053
mRNA-based biologic Drug: Antipyretic participants will receive oral premedication prior to infusion
Other Names:
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 |
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Experimental: 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.
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Biological: UX053
mRNA-based biologic Drug: Antipyretic participants will receive oral premedication prior to infusion
Other Names:
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: 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.
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Biological: UX053
mRNA-based biologic Drug: Antipyretic participants will receive oral premedication prior to infusion
Other Names:
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: 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.
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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
Other Names:
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: 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.
|
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
Other Names:
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: 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.
|
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
Other Names:
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 :
- 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 :
- PK parameters of AGL mRNA: time of maximum observed concentration (Tmax) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: maximum concentration (Cmax) [ Time Frame: From pre-infusion up to Day 28 ]
- 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 ]
- PK parameters of AGL mRNA: AUC from time 0 to infinity (AUCinf) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: AUC from time 0 to end of dosing period (AUCtau; RD cohorts only) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: accumulation ratio (calculated as AUC after repeat dose / AUC after a single dose; RAUC; RD cohorts only) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: time of last measurable concentration (Tlast) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: half life (T1/2) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: clearance (CL) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of AGL mRNA: volume of distribution in a steady state (Vss) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: Tmax [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: Cmax [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: AUClast [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: AUCinf [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: AUCtau; RD cohorts only [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: accumulation ratio (calculated as AUC after repeat dose / AUC after a single dose; RAUC; RD cohorts only) [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: Tlast [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: T1/2 [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: CL [ Time Frame: From pre-infusion up to Day 28 ]
- PK parameters of ATX95: Vss [ 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.
| 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
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
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
Locations
| United States, California | |
| University of California, Irvine | |
| Orange, California, United States, 92868 | |
| United States, Georgia | |
| Rare Disease Research | |
| Atlanta, Georgia, United States, 30329 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Texas | |
| University of Texas, Health Science Center of Houston | |
| Houston, Texas, United States, 77030 | |
| Canada, Ontario | |
| The Ottawa Hospital Research Institute | |
| Ottawa, Ontario, Canada, K1Y4E9 | |
| France | |
| Hopital Femme Mere Enfant | |
| Bron, Cedex, France, 69677 | |
| Institut de Myologie - Hopital Antoine Béclère | |
| Clamart, France, 92140 | |
| Italy | |
| Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico | |
| Milan, Italy, 20122 | |
| Spain | |
| Hospital Universitario 12 de Octubre | |
| Madrid, Spain, 28041 | |
| United Kingdom | |
| Salford Royal NHS Foundation Trust | |
| Salford, Greater Manchester, United Kingdom, M68HD | |
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
| Study Director: | Medical Director | Ultragenyx Pharmaceutical Inc |
Additional Information:
| 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: | April 4, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Glycogen Storage Disease Glycogen Storage Disease Type III Disease Metabolic Diseases Pathologic Processes 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 |