Clinical Trial Results:
Phase 2, Randomized, Double-Blind, Placebo Controlled, Nested Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARCT-810 in Adolescent and Adult Participants with Ornithine Transcarbamylase Deficiency
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Summary
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EudraCT number |
2021-001081-38 |
Trial protocol |
BE ES FR SE IT |
Global end of trial date |
31 Oct 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Nov 2025
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First version publication date |
23 Nov 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ARCT-810-03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05526066 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Arcturus Therapeutics, Inc.
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Sponsor organisation address |
10628 Science Center Dr #250, San Diego, United States, 92121
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Public contact |
Arcturus Therapeutics, Inc., Arcturus Therapeutics, Inc., 858 900-2660, clinicaltrials@arcturusrx.com
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Scientific contact |
Arcturus Therapeutics, Inc., Arcturus Therapeutics, Inc., 858 900-2660, clinicaltrials@arcturusrx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Apr 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Oct 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Oct 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess safety and tolerability of ARCT-810 in adult and adolescent (≥12 years) participants with ornithine transcarbamylase (OTC) deficiency.
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Protection of trial subjects |
This study was run according to the principles of the International Council for Harmonization (ICH) harmonized tripartite guideline E6(R2): Good Clinical Practices (GCP). The investigator performed all aspects of this study in accordance with the ethical principles that have their origin in the Declaration of Helsinki, the protocol, and all national, state, and local laws or regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Oct 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Spain: 3
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Country: Number of subjects enrolled |
United Kingdom: 2
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Worldwide total number of subjects |
8
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EEA total number of subjects |
6
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
4
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Adults (18-64 years) |
4
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was planned with two ascending dose cohorts (Cohort A and Cohort B). The study was terminated based on the sponsor’s decision around enrollment rate prior to initiating Cohort B. | ||||||||||||||||||
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Pre-assignment
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Screening details |
The study comprised at least a 28-day (4-week) Screening and Diet Run-in (Stabilization) Period running concurrently. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ARCT-810 | ||||||||||||||||||
Arm description |
On Day 1, participants received a single dose of ARCT-810 via intravenous infusion. Participants then received a further 5 doses of ARCT-810 on Days 15, 29, 43, 57 and 71. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
ARCT-810
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
As specified in the arm description.
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
On Day 1, participants received a single dose of placebo via intravenous infusion. Participants then received a further 5 doses of placebo on Days 15, 29, 43, 57 and 71. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
As specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
ARCT-810
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Reporting group description |
On Day 1, participants received a single dose of ARCT-810 via intravenous infusion. Participants then received a further 5 doses of ARCT-810 on Days 15, 29, 43, 57 and 71. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
On Day 1, participants received a single dose of placebo via intravenous infusion. Participants then received a further 5 doses of placebo on Days 15, 29, 43, 57 and 71. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ARCT-810
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Reporting group description |
On Day 1, participants received a single dose of ARCT-810 via intravenous infusion. Participants then received a further 5 doses of ARCT-810 on Days 15, 29, 43, 57 and 71. | ||
Reporting group title |
Placebo
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Reporting group description |
On Day 1, participants received a single dose of placebo via intravenous infusion. Participants then received a further 5 doses of placebo on Days 15, 29, 43, 57 and 71. | ||
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End point title |
Number of Participants with Adverse Events (AEs) and Treatment-related AEs [1] | |||||||||||||||
End point description |
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A treatment-related AE was defined as an AE that was considered related to the medicinal (investigational) product by the investigator. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Measured in the safety population, which included all participants who were randomized and received any study drug.
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End point type |
Primary
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End point timeframe |
Up to approximately 28 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were planned for this endpoint. |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Area Under the Plasma Concentration Versus Time Curve (AUC) from Time Zero to the Last Quantifiable Time Point (AUClast) of ARCT-810 mRNA and Lipid Components [2] | ||||||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the pharmacokinetic (PK) population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 71
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| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
The Maximum Observed Plasma Concentration (Cmax) of ARCT-810 mRNA and Lipid Components [3] | ||||||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the PK population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "n" = number of participants evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 71
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
The Time at which Cmax Occurred (Tmax) of ARCT-810 mRNA and Lipid Components [4] | ||||||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the PK population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "n" = number of participants evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 71
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| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Plasma AUC From Time Zero Extrapolated to Infinity (AUCinf) of ARCT-810 mRNA and Lipid Components [5] | ||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the PK population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Day 1
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Terminal Half-life (T1/2) of ARCT-810 mRNA and Lipid Components [6] | ||||||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the PK population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint. 9999 = data not calculable because there was insufficient data (n=2) to calculate a geometric mean.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 71
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Total Body Clearance (CL) of ARCT-810 mRNA and Lipid Components [7] | ||||||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the PK population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint. 9999 = data not calculable because there was insufficient data (n=2) to calculate a geometric mean.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 71
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Volume of Distribution at Steady State (Vss) of ARCT-810 mRNA and Lipid Components [8] | ||||||||||||||||
End point description |
Pharmacokinetic parameters of ARCT-810 components (mRNA and lipid) were derived from plasma concentrations. Measured in the PK population, which included all participants who were randomized and received at least 1 complete infusion of study drug and had at least one evaluable PK result. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint. 9999 = data not calculable because there was insufficient data (n=2) to calculate a geometric mean.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 71
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| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data were collected and are reported for the investigational treatment arm only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change from Baseline in Peak Plasma Concentration for 13C-urea | |||||||||||||||||||||
End point description |
Measured in the Pharmacodynamic Evaluable Population, which included all participants who were randomized and received study drug and had completed the relevant evaluations at Baseline and at the specified time point. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Days 30, 72 and 78
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change from Baseline in Area Under Curve for 13C-urea | |||||||||||||||||||||
End point description |
Measured in the Pharmacodynamic Evaluable Population, which included all participants who were randomized and received study drug and had completed the relevant evaluations at Baseline and at the specified time point. "Number of subjects analyzed" = participants evaluable for the outcome measure. "n" = number of participants evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Days 30, 72 and 78
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change from Baseline in Area Under the Curve for 24-hour Ammonia Profile | ||||||||||||
End point description |
As per updated pre-planned analysis, data were not collected for 24-hour ammonia profile.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 72
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| Notes [9] - As per updated pre-planned analysis, data were not collected for 24-hour ammonia profile. [10] - As per updated pre-planned analysis, data were not collected for 24-hour ammonia profile. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in Peak Plasma Ammonia for 24-hour Ammonia Profile | ||||||||||||
End point description |
As per updated pre-planned analysis, data were not collected for 24-hour ammonia profile.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 72
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| Notes [11] - As per updated pre-planned analysis, data were not collected for 24-hour ammonia profile. [12] - As per updated pre-planned analysis, data were not collected for 24-hour ammonia profile. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to approximately 28 weeks
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Adverse event reporting additional description |
Mortality, treatment-emergent serious and non-serious adverse events were measured in the safety population, which included all participants who were randomized and received any study drug.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
On Day 1, participants received a single dose of placebo via intravenous infusion. Participants then received a further 5 doses of placebo on Days 15, 29, 43, 57 and 71. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ARCT-810
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Reporting group description |
On Day 1, participants received a single dose of ARCT-810 via intravenous infusion. Participants then received a further 5 doses of ARCT-810 on Days 15, 29, 43, 57 and 71. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 Jul 2021 |
Changes included:
• Section 6.2.3.1 Plasma Ammonia Levels: Deleted reference to the hyperammonemia questionnaire, as there is not one in this study. Also clarified that storage temperature for plasma samples.
• Section 7.1 Study Drug Description: Updated study drug stability data.
• Section 8.1.2 Premedication information updated
• Section 8.1.4 Anaphylaxis Precautions updated
• Appendix 1: Schedule of Assessments updated
• Appendix 2: List of Laboratory Analytes updated |
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30 Sep 2021 |
Changes included:
• Section 5.1 Inclusion Criteria updated
• Section 6.2.4 and Appendix 1: Quality-of-life instrument was added to the protocol to include a patient-reported outcome measure prior to treatment and at the end of the 6-dose treatment course. |
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01 Dec 2021 |
Changes included:
• Section 5.2 Exclusion Criterion updated
• Section 8.1.2 Premedication clarified
• Appendix 1 Schedule of Assessments updated |
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10 Mar 2022 |
Changes included:
• Section 3.7 Overall Study Duration and Follow-up and Section 5.2 Exclusion Criterion updated
• Section 5.1 Inclusion Criterion updated
• Section 5.2 Exclusion Criterion and Section 8.1.1 Infection Prior to Dosing updated
• Section 5.2 Exclusion Criterion #15 updated |
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11 Feb 2023 |
Changes included:
• Sections 1.2.3 and 10.5.4 (Exploratory Endpoints) updated
• Sections 2.3.1 and 2.4.4: Updated Dose/regimen Rationale and Clinical Experience sections
• Section 2.5.2 (Risk Assessment): Table 2 safety considerations updated with new, blinded information about the ARCT-810-02 study experience.
• Section 3.2 (Study Design): Corrected error
• Section 3.11 (Dose Limiting Toxicity): Removed ‘serious adverse event (SAE)’ from the criteria for dose limiting toxicity (DLT).
• Section 4.4 (Blinding): Clarified that if the infusion nurse is unblinded, a separate blinded person must do the visit assessments to the participant.
• Section 5.1 Inclusion Criteria updated
• Section 5.2 Exclusion Criteria updated
• Section 6.1 (Study Schedule): Minor changes in wording were made
• Section 8.1.2 (Premedication) updated
• Sections 8.1.2, 8.1.3 (Table 5), 8.9.1, and 2.5.2 (Table 2) updated for participants who experienced an infusion-related reaction (IRR)
• Section 8.1.3 (Infusion-Related Reactions): Added the definition of IRR and added Table 5 that includes the IRR grading system and incorporates management recommendations that were previously listed in the text. Also clarified the documentation expectations for IRR.
• Section 8.1.4 (Anaphylaxis Precautions): Added IV cetirizine as a treatment option.
• Section 8.3 (Study Drug Administration) and Appendix 4: The study drug infusion procedure was modified
• Section 8.5.3 (Safety Monitoring Rules for IRR): Minor additions
• Appendix 1: Schedule of Assessments updated
• Appendix 2: List of Laboratory Analytes updated |
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16 Jun 2023 |
Changes included:
• Section 2.3.1 Dose and Regimen: Removed redundant information on IRRs and updated the initial infusion procedure.
• Section 2.4.2.2 Drug Product ARCT-810: Changed the title of Figure 3 to correct the description of what is presented.
• Section 2.4.4 Clinical Experience: Edited the information to include updated safety data from ongoing studies.
• Section 2.5.2 Risk Assessment: Edited the information to include updated information on IRRs from the ongoing studies; added revised mitigation procedures to reduce risk.
• Section 3.2 Study Design: Updated cohort and dose information. Changed the Screening duration to be at least 4 weeks with no maximum duration.
• Section 3.7 Overall Study Duration and Follow-up: Specified that Screening duration must be at least 4 weeks, allowing extensions for flexibility. Deleted unnecessary language.
• Section 3.11 Dose-Limiting Toxicity: Clarified the definition of a DLT.
• Section 3.13 Study Stopping Rules: Removed contradictory wording and clarified rules for terminating the study based on discussions with the Safety Review Committee (SRC) after the occurrence of the suspected unexpected serious adverse reaction in this study.
• Section 8.1 Infection prior to dosing: Specified that if Screening needs to be extended beyond 6 weeks, the medical monitor should be consulted on whether any assessments need to be repeated prior to the first dose.
• Section 8.1.2 Premedication: Updated
• Section 8.1.4 Anaphylaxis Procedures: Updated
• Section 8.5.1 Safety Monitoring Rules for Liver Chemistry Tests updated
• Appendix 1 Schedule of Assessments updated |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated based on the sponsor’s decision around enrollment rate prior to initiating Cohort B. | |||
