Glycogen Storage Disease Type III
Conditions
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).
Interventions
BIOLOGICALUX053
mRNA-based biologic
OTHERPlacebo
consists of the same components as the formulation buffer for UX053
DRUGAntipyretic
participants will receive oral premedication prior to infusion
DRUGH2 Blocker
participants will receive oral premedication prior to infusion
DRUGH1 Blocker
participants will receive oral premedication prior to infusion
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | 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). |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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: Clearance (CL) | 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: Volume of Distribution at Steady State (Vss) | 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 |
Countries
Italy, Spain, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| SAD Cohort 1: 0.05 mg/kg Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053. | 4 |
| SAD Cohort 2: 0.10 mg/kg Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | SAD Cohort 2: 0.10 mg/kg | Total | SAD Cohort 1: 0.05 mg/kg |
|---|---|---|---|
| Age, Continuous | 43.53 years STANDARD_DEVIATION 10.1 | 47.86 years STANDARD_DEVIATION 8.77 | 52.20 years STANDARD_DEVIATION 5.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 8 |
| other Total, other adverse events | 3 / 4 | 4 / 4 | 7 / 8 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 8 |
Outcome results
Primary
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).
Time frame: From first dose of study drug through the end of study (up to Day 90)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Serious Related TEAE | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Any TEAE | 3 Participants |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Study Discontinuation | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Treatment Discontinuation | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Related TEAE | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Death | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Dose Reduction | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Serious TEAE | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Dose Interruption | 0 Participants |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Dose Interruption | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Any TEAE | 4 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Serious TEAE | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Related TEAE | 1 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | Serious Related TEAE | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE With Maximum Severity Grade 1 | 4 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Study Discontinuation | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Treatment Discontinuation | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Death | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | TEAE Leading to Dose Reduction | 0 Participants |
| SAD Cohort 2: 0.10 mg/kg | 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 |
Secondary
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | 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 | 72.15 ng/mL | Standard Deviation 60.99 |
| SAD Cohort 2: 0.10 mg/kg | 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 | 8585.00 ng/mL | Standard Deviation 4439.62 |
Secondary
PK of AGL mRNA and the Excipient ATX95: Clearance (CL)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Clearance (CL) | AGL mRNA | 21.42 mL/h/kg | Standard Deviation 7.16 |
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Clearance (CL) | ATX95 | 39.80 mL/h/kg | Standard Deviation 4.62 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Clearance (CL) | AGL mRNA | 55.51 mL/h/kg | Standard Deviation 52.36 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Clearance (CL) | ATX95 | 94.73 mL/h/kg | Standard Deviation 69.18 |
Secondary
PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½) | ATX95 | 18.0 hours | Standard Deviation 7.5 |
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½) | AGL mRNA | 53.8 hours | Standard Deviation 4.3 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½) | AGL mRNA | 44.8 hours | Standard Deviation 11.6 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½) | ATX95 | 32.3 hours | Standard Deviation 32.2 |
Secondary
PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax)
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax) | AGL mRNA | 6.10 hours |
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax) | ATX95 | 4.20 hours |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax) | AGL mRNA | 6.15 hours |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax) | ATX95 | 3.90 hours |
Secondary
PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf) | AGL mRNA | 3948.5 ng*h/mL | Standard Deviation 4178.7 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf) | ATX95 | 31425.0 ng*h/mL | Standard Deviation 20758 |
Secondary
PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last) | AGL mRNA | 3931.0 ng*h/mL | Standard Deviation 4191.2 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last) | ATX95 | 31350.0 ng*h/mL | Standard Deviation 20738.8 |
Secondary
PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD Cohort 1: 0.05 mg/kg | 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 |
| SAD Cohort 1: 0.05 mg/kg | PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss) | ATX95 | 167.8 mL/kg | Standard Deviation 76 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss) | AGL mRNA | 3993.3 mL/kg | Standard Deviation 3546.5 |
| SAD Cohort 2: 0.10 mg/kg | PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss) | ATX95 | 741.5 mL/kg | Standard Deviation 874 |