Back to resultsStudy for Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810
Primary Purpose
Ornithine Transcarbamylase Deficiency, OTC Deficiency, OTCD
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARCT-810
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ornithine Transcarbamylase Deficiency focused on measuring OTC, OTCD, Ornithine, Transcarbamylase, mRNA, Ornithine Transcarbamylase Deficiency, OTC Deficiency
Eligibility Criteria
Key Inclusion Criteria:
- Adequate cognitive ability to understand study requirements and give informed consent
- Males and females aged 12 to 65 years inclusive, at Screening
- Documented diagnosis of OTC deficiency confirmed with genetic testing
- Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year)
- Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days.
- BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and >5th percentile for adolescents ≥12 to 17 years
- Must be willing to adhere to contraception guidelines
Key Exclusion Criteria:
- History of OTC gene therapy, hepatocyte or stem cell transplantation
- History of other medical conditions that may make the participant unsuitable for inclusion or could interfere with study participation (e.g., uncontrolled hypertension or diabetes, malignancy, HIV, hepatitis B or C)
- History of severe allergic reaction to liposomal or PEG-containing products
- Abuse of illicit drugs, medications or alcohol
- Clinically significant laboratory abnormalities on screening labs
Sites / Locations
- Cliniques Universitaires Saint LucRecruiting
- Hospital Clínic de BarcelonaRecruiting
- Hospital Sant Joan de DéuRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico UniversitarioRecruiting
- Karolinska Universitetssjukhuset - Astrid Lindgrens BarnsjukhusRecruiting
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital BirminghamRecruiting
- Great Ormond Street Hospital for Children NHS Foundation TrustRecruiting
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and NeurosurgeryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ARCT-810
Placebo, Normal Saline
Arm Description
Participants receive an initial intravenous (IV) infusion ARCT-810. If considered safe and well tolerated, participants will receive up to 5 additional IV infusions of ARCT-810 administered at 14-day intervals.
Participants receive an initial IV infusion of placebo. If considered safe and well tolerated, participants receive up to 5 additional IV infusions of placebo administered at 14-day intervals.
Outcomes
Primary Outcome Measures
Incidence, severity and dose-relationship of adverse events (AEs)
Safety and tolerability of ARCT-810 assessed by determining the number of AEs by dose
Secondary Outcome Measures
Plasma concentration area under the curve after first and last doses of ARCT-810
Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point
Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810
The maximum observed plasma concentration (Cmax)
Time at which Cmax occurred after first and last doses of ARCT-810
The time at which Cmax occurred (Tmax)
AUC0-inf after first and last doses of ARCT-810
Plasma AUC from time zero extrapolated to infinity
AUCExtrap after first and last doses of ARCT-810
The relative portion of AUC0-inf extrapolated beyond AUC0-t
T1/2 after first and last doses of ARCT-810
Terminal half-life
MRT0-inf after first and last doses of ARCT-810
The mean residence time extrapolated to infinity
CL after first and last doses of ARCT-810
Total body clearance, calculated as dose divided by AUC0-inf
Vss after first and last doses of ARCT-810
Volume of distribution
Urea Cycle Function
Change from baseline in urea cycle function as measured by 13C-urea assay
Plasma Ammonia
Change from baseline in urea cycle function as measured by 24-hour plasma ammonia profile
Full Information
NCT ID
NCT05526066
First Posted
August 8, 2022
Last Updated
April 6, 2023
Sponsor
Arcturus Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05526066
Brief Title
Study for Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arcturus Therapeutics, 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 is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.
Detailed Description
This study is a Phase 2, randomized, placebo-controlled study of ARCT-810 in people living with OTC deficiency 12 years of age and older. After a 4-6-week screening and diet stabilization period, participants will be randomized 3:1 to receive ARCT-810 or placebo. Following the first dose and safety evaluation, participants will receive up to an additional 5 doses of ARCT-810 or placebo, each separated by 14 days. The treatment period is followed by a 12-week observation period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ornithine Transcarbamylase Deficiency, OTC Deficiency, OTCD
Keywords
OTC, OTCD, Ornithine, Transcarbamylase, mRNA, Ornithine Transcarbamylase Deficiency, OTC Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
On Day 1, participants will receive a single dose of Study Drug via intravenous infusion.
If the safety observations are considered acceptable, that participant will enter the multiple-dose portion of the study where they will receive a further 5 doses of Study Drug on Days 15, 29, 43, 57 and 71.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-Blinded
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ARCT-810
Arm Type
Experimental
Arm Description
Participants receive an initial intravenous (IV) infusion ARCT-810. If considered safe and well tolerated, participants will receive up to 5 additional IV infusions of ARCT-810 administered at 14-day intervals.
Arm Title
Placebo, Normal Saline
Arm Type
Placebo Comparator
Arm Description
Participants receive an initial IV infusion of placebo. If considered safe and well tolerated, participants receive up to 5 additional IV infusions of placebo administered at 14-day intervals.
Intervention Type
Biological
Intervention Name(s)
ARCT-810
Intervention Description
ARCT-810 is messenger RNA (mRNA) coding for Ornithine Transcarbamylase (OTC) formulated in a lipid nanoparticle (LNP) under development.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Normal Saline
Primary Outcome Measure Information:
Title
Incidence, severity and dose-relationship of adverse events (AEs)
Description
Safety and tolerability of ARCT-810 assessed by determining the number of AEs by dose
Time Frame
Week 23
Secondary Outcome Measure Information:
Title
Plasma concentration area under the curve after first and last doses of ARCT-810
Description
Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point
Time Frame
Up to 17 Weeks
Title
Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810
Description
The maximum observed plasma concentration (Cmax)
Time Frame
Up to 17 Weeks
Title
Time at which Cmax occurred after first and last doses of ARCT-810
Description
The time at which Cmax occurred (Tmax)
Time Frame
Up to 17 Weeks
Title
AUC0-inf after first and last doses of ARCT-810
Description
Plasma AUC from time zero extrapolated to infinity
Time Frame
Up to 17 Weeks
Title
AUCExtrap after first and last doses of ARCT-810
Description
The relative portion of AUC0-inf extrapolated beyond AUC0-t
Time Frame
Up to 17 Weeks
Title
T1/2 after first and last doses of ARCT-810
Description
Terminal half-life
Time Frame
Up to 17 Weeks
Title
MRT0-inf after first and last doses of ARCT-810
Description
The mean residence time extrapolated to infinity
Time Frame
Up to 17 Weeks
Title
CL after first and last doses of ARCT-810
Description
Total body clearance, calculated as dose divided by AUC0-inf
Time Frame
Up to 17 Weeks
Title
Vss after first and last doses of ARCT-810
Description
Volume of distribution
Time Frame
Up to 17 Weeks
Title
Urea Cycle Function
Description
Change from baseline in urea cycle function as measured by 13C-urea assay
Time Frame
Week 12
Title
Plasma Ammonia
Description
Change from baseline in urea cycle function as measured by 24-hour plasma ammonia profile
Time Frame
Week 11
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Adequate cognitive ability to understand study requirements and give informed consent
Males and females aged 12 to 65 years inclusive, at Screening
Documented diagnosis of OTC deficiency confirmed with genetic testing
Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year)
Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days.
BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and >5th percentile for adolescents ≥12 to 17 years
Must be willing to adhere to contraception guidelines
Key Exclusion Criteria:
History of OTC gene therapy, hepatocyte or stem cell transplantation
History of other medical conditions that may make the participant unsuitable for inclusion or could interfere with study participation (e.g., uncontrolled hypertension or diabetes, malignancy, HIV, hepatitis B or C)
History of severe allergic reaction to liposomal or PEG-containing products
Abuse of illicit drugs, medications or alcohol
Clinically significant laboratory abnormalities on screening labs
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Geller, MD
Phone
224-727-7636
Email
davidg@arcturusrx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Elizabeth Colon
Phone
231-730-7300
Email
elizabeth.colon@arcturusrx.com
Facility Information:
Facility Name
Cliniques Universitaires Saint Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Etienne Sokal, MD
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pedro Juan Pedro Juan, MD
Phone
+34 722862292
Email
pjmoreno@clinic.cat
Facility Name
Hospital Sant Joan de Déu
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Àngels García Cazorla, MD
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Montserrat Morales, MD
Email
montserrat.morales@salud.madrid.org
Facility Name
Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Luz Couce Pico, MD
Phone
+34 98 195 11 34
Email
maria.luz.couce.pico@sergas.es
Facility Name
Karolinska Universitetssjukhuset - Astrid Lindgrens Barnsjukhus
City
Stockholm
ZIP/Postal Code
SE- 171 64
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Svetlana Lajic, MD
Phone
+46-73-9489862
Email
svetlana.lajic@ki.se
Facility Name
University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
City
Birmingham
State/Province
UK
ZIP/Postal Code
B15 2PR
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlotte Dawson, MD
Phone
44 (0) 121 371 6983
Email
charlotte.dawson@uhb.nhs.uk
Facility Name
Great Ormond Street Hospital for Children NHS Foundation Trust
City
London
State/Province
UK
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Spyros Batzios, MD
Phone
+44 02074059200
Email
spyros.batzios@gosh.nhs.uk
Facility Name
University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robin Lachmann, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study for Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810
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