Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III) (NCT NCT04990388)
NCT ID: NCT04990388
Last Updated: 2024-04-16
Results Overview
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).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
From first dose of study drug through the end of study (up to Day 90)
Results posted on
2024-04-16
Participant Flow
A total of 9 participants enrolled in this study; 1 withdrew consent prior to group assignment, did not receive study drug, and was not included in any data table. Eight participants enrolled and were treated; all completed participation in the single ascending dose (SAD) cohorts and were included in the final analysis. None of these participants were randomized, as they were only in SAD cohorts, and none rolled into an open label-repeated dose cohort, as the study discontinued early.
Participant milestones
| Measure |
SAD Cohort 1: 0.05 mg/kg
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability, and Pharmacokinetics of UX053 in Patients With Glycogen Storage Disease Type III (GSD III)
Baseline characteristics by cohort
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Continuous
|
52.20 years
STANDARD_DEVIATION 5.21 • n=5 Participants
|
43.53 years
STANDARD_DEVIATION 10.10 • n=7 Participants
|
47.86 years
STANDARD_DEVIATION 8.77 • n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug through the end of study (up to Day 90)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).
Outcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
Any TEAE
|
3 Participants
|
4 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
Serious TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
Related TEAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
Serious Related TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE With Maximum Severity Grade 5
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE With Maximum Severity Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE With Maximum Severity Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE With Maximum Severity Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE With Maximum Severity Grade 1
|
3 Participants
|
4 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE Leading to Study Discontinuation
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE Leading to Treatment Discontinuation
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE Leading to Death
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE Leading to Dose Reduction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes
TEAE Leading to Dose Interruption
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
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)
AGL mRNA
|
56.00 ng/mL
Standard Deviation 30.59
|
72.15 ng/mL
Standard Deviation 60.99
|
|
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)
ATX95
|
7010.00 ng/mL
Standard Deviation 1360.71
|
8585.00 ng/mL
Standard Deviation 4439.62
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax)
AGL mRNA
|
6.10 hours
Interval 4.5 to 7.9
|
6.15 hours
Interval 2.8 to 8.1
|
|
PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax)
ATX95
|
4.20 hours
Interval 3.0 to 4.4
|
3.90 hours
Interval 3.0 to 4.1
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last)
AGL mRNA
|
2567.5 ng*h/mL
Standard Deviation 956.4
|
3931.0 ng*h/mL
Standard Deviation 4191.2
|
|
PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last)
ATX95
|
25350.0 ng*h/mL
Standard Deviation 3087.1
|
31350.0 ng*h/mL
Standard Deviation 20738.8
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf)
AGL mRNA
|
2572.5 ng*h/mL
Standard Deviation 958.0
|
3948.5 ng*h/mL
Standard Deviation 4178.7
|
|
PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf)
ATX95
|
25375.0 ng*h/mL
Standard Deviation 3055.5
|
31425.0 ng*h/mL
Standard Deviation 20758.0
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½)
AGL mRNA
|
53.8 hours
Standard Deviation 4.3
|
44.8 hours
Standard Deviation 11.6
|
|
PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½)
ATX95
|
18.0 hours
Standard Deviation 7.5
|
32.3 hours
Standard Deviation 32.2
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
PK of AGL mRNA and the Excipient ATX95: Clearance (CL)
AGL mRNA
|
21.42 mL/h/kg
Standard Deviation 7.16
|
55.51 mL/h/kg
Standard Deviation 52.36
|
|
PK of AGL mRNA and the Excipient ATX95: Clearance (CL)
ATX95
|
39.80 mL/h/kg
Standard Deviation 4.62
|
94.73 mL/h/kg
Standard Deviation 69.18
|
SECONDARY outcome
Timeframe: 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 infusionOutcome measures
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 Participants
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 Participants
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
|---|---|---|
|
PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss)
AGL mRNA
|
1638.8 mL/kg
Standard Deviation 722.4
|
3993.3 mL/kg
Standard Deviation 3546.5
|
|
PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss)
ATX95
|
167.8 mL/kg
Standard Deviation 76.0
|
741.5 mL/kg
Standard Deviation 874.0
|
Adverse Events
SAD Cohort 1: 0.05 mg/kg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
SAD Cohort 2: 0.10 mg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Total
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
SAD Cohort 1: 0.05 mg/kg
n=4 participants at risk
Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053.
|
SAD Cohort 2: 0.10 mg/kg
n=4 participants at risk
Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053.
|
Total
n=8 participants at risk
Participants received a single, peripheral IV infusion of a 0.05 or 0.10 mg/kg dose of UX053.
|
|---|---|---|---|
|
General disorders
Pyrexia
|
25.0%
1/4 • Up to 90 days after dosing.
|
0.00%
0/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Immune system disorders
Seasonal Allergy
|
25.0%
1/4 • Up to 90 days after dosing.
|
0.00%
0/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Injury, poisoning and procedural complications
Joint Injury
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
25.0%
1/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
25.0%
2/8 • Up to 90 days after dosing.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Skin and subcutaneous tissue disorders
Rash
|
25.0%
1/4 • Up to 90 days after dosing.
|
0.00%
0/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Vascular disorders
Haematoma
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • Up to 90 days after dosing.
|
0.00%
0/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Infections and infestations
Ear infection bacterial
|
25.0%
1/4 • Up to 90 days after dosing.
|
0.00%
0/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/4 • Up to 90 days after dosing.
|
25.0%
1/4 • Up to 90 days after dosing.
|
12.5%
1/8 • Up to 90 days after dosing.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER