Back to resultsSafety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III)
Primary Purpose
Glycogen Storage Disease Type III
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
UX053
Placebo
Antipyretic
H2 Blocker
H1 Blocker
Sponsored by
About this trial
This is an interventional treatment trial for Glycogen Storage Disease Type III
Eligibility 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
Sites / Locations
- University of California, Irvine
- Rare Disease Research
- Children's Hospital of Philadelphia
- University of Texas, Health Science Center of Houston
- The Ottawa Hospital Research Institute
- Hopital Femme Mere Enfant
- Institut de Myologie - Hopital Antoine Béclère
- Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
- Hospital Universitario 12 de Octubre
- Salford Royal NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
UX053 Dose Level 1S ->OL-1R
UX053 Dose Level 2S->OL-2R
UX053 Dose Level 3S->OL-3R
UX053 or Placebo Dose Level DB-1R
UX053 Dose Level DB-2R
UX053 Dose Level DB-3R
Arm 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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Incidence and severity of treatment-emergent adverse events (TEAEs), serious TEAEs, and related TEAEs in the SAD and RD Periods
Secondary Outcome Measures
PK parameters of AGL mRNA: time of maximum observed concentration (Tmax)
PK parameters of AGL mRNA: maximum concentration (Cmax)
PK parameters of AGL mRNA: area under the concentration-time curve (AUC) from time 0 to the last measurable concentration (AUClast)
PK parameters of AGL mRNA: AUC from time 0 to infinity (AUCinf)
PK parameters of AGL mRNA: AUC from time 0 to end of dosing period (AUCtau; RD cohorts only)
PK parameters of AGL mRNA: accumulation ratio (calculated as AUC after repeat dose / AUC after a single dose; RAUC; RD cohorts only)
PK parameters of AGL mRNA: time of last measurable concentration (Tlast)
PK parameters of AGL mRNA: half life (T1/2)
PK parameters of AGL mRNA: clearance (CL)
PK parameters of AGL mRNA: volume of distribution in a steady state (Vss)
PK parameters of ATX95: Tmax
PK parameters of ATX95: Cmax
PK parameters of ATX95: AUClast
PK parameters of ATX95: AUCinf
PK parameters of ATX95: AUCtau; RD cohorts only
PK parameters of ATX95: accumulation ratio (calculated as AUC after repeat dose / AUC after a single dose; RAUC; RD cohorts only)
PK parameters of ATX95: Tlast
PK parameters of ATX95: T1/2
PK parameters of ATX95: CL
PK parameters of ATX95: Vss
Full Information
NCT ID
NCT04990388
First Posted
July 26, 2021
Last Updated
March 30, 2023
Sponsor
Ultragenyx Pharmaceutical Inc
1. Study Identification
Unique Protocol Identification Number
NCT04990388
Brief Title
Safety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III)
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision not related to safety concerns
Study Start Date
October 18, 2021 (Actual)
Primary Completion Date
March 20, 2023 (Actual)
Study Completion Date
March 20, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
Detailed 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glycogen Storage Disease Type III
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
UX053 Dose Level 1S ->OL-1R
Arm Type
Experimental
Arm 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.
Arm Title
UX053 Dose Level 2S->OL-2R
Arm Type
Experimental
Arm 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.
Arm Title
UX053 Dose Level 3S->OL-3R
Arm Type
Experimental
Arm 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.
Arm Title
UX053 or Placebo Dose Level DB-1R
Arm Type
Experimental
Arm 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.
Arm Title
UX053 Dose Level DB-2R
Arm Type
Experimental
Arm 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.
Arm Title
UX053 Dose Level DB-3R
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
UX053
Intervention Description
mRNA-based biologic
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
consists of the same components as the formulation buffer for UX053
Intervention Type
Drug
Intervention Name(s)
Antipyretic
Other Intervention Name(s)
paracetamol, acetaminophen, ibuprofen
Intervention Description
participants will receive oral premedication prior to infusion
Intervention Type
Drug
Intervention Name(s)
H2 Blocker
Other Intervention Name(s)
famotidine
Intervention Description
participants will receive oral premedication prior to infusion
Intervention Type
Drug
Intervention Name(s)
H1 Blocker
Other Intervention Name(s)
cetirizine
Intervention Description
participants will receive oral premedication prior to infusion
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
PK parameters of AGL mRNA: time of maximum observed concentration (Tmax)
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of AGL mRNA: maximum concentration (Cmax)
Time Frame
From pre-infusion up to Day 28
Title
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
Title
PK parameters of AGL mRNA: AUC from time 0 to infinity (AUCinf)
Time Frame
From pre-infusion up to Day 28
Title
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
Title
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
Title
PK parameters of AGL mRNA: time of last measurable concentration (Tlast)
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of AGL mRNA: half life (T1/2)
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of AGL mRNA: clearance (CL)
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of AGL mRNA: volume of distribution in a steady state (Vss)
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: Tmax
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: Cmax
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: AUClast
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: AUCinf
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: AUCtau; RD cohorts only
Time Frame
From pre-infusion up to Day 28
Title
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
Title
PK parameters of ATX95: Tlast
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: T1/2
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: CL
Time Frame
From pre-infusion up to Day 28
Title
PK parameters of ATX95: Vss
Time Frame
From pre-infusion up to Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Rare Disease Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas, Health Science Center of Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y4E9
Country
Canada
Facility Name
Hopital Femme Mere Enfant
City
Bron
State/Province
Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Institut de Myologie - Hopital Antoine Béclère
City
Clamart
ZIP/Postal Code
92140
Country
France
Facility Name
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
State/Province
Greater Manchester
ZIP/Postal Code
M68HD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://ultrarareadvocacy.com/glycogen-storage-disease-type-iii-gsdiii/
Description
Ultragenyx Patient Advocacy/GSD III Disease Information
Learn more about this trial
Safety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III)
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