- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05526066
Study for Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810
April 6, 2023 updated by: Arcturus Therapeutics, Inc.
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
The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.
Study Overview
Status
Recruiting
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
24
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: David Geller, MD
- Phone Number: 224-727-7636
- Email: davidg@arcturusrx.com
Study Contact Backup
- Name: Elizabeth Colon
- Phone Number: 231-730-7300
- Email: elizabeth.colon@arcturusrx.com
Study Locations
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Bruxelles, Belgium, 1200
- Recruiting
- Cliniques Universitaires Saint Luc
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Contact:
- Etienne Sokal, MD
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Barcelona, Spain
- Recruiting
- Hospital Clínic de Barcelona
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Contact:
- Pedro Juan Pedro Juan, MD
- Phone Number: +34 722862292
- Email: pjmoreno@clinic.cat
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Barcelona, Spain
- Recruiting
- Hospital Sant Joan de Déu
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Contact:
- Àngels García Cazorla, MD
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Madrid, Spain, 28041
- Recruiting
- Hospital Universitario 12 de Octubre
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Contact:
- Montserrat Morales, MD
- Email: montserrat.morales@salud.madrid.org
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Santiago de Compostela, Spain, 15706
- Recruiting
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Contact:
- Maria Luz Couce Pico, MD
- Phone Number: +34 98 195 11 34
- Email: maria.luz.couce.pico@sergas.es
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Stockholm, Sweden, SE- 171 64
- Recruiting
- Karolinska Universitetssjukhuset - Astrid Lindgrens barnsjukhus
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Contact:
- Svetlana Lajic, MD
- Phone Number: +46-73-9489862
- Email: svetlana.lajic@ki.se
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London, United Kingdom
- Recruiting
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Contact:
- Robin Lachmann, MD
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UK
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Birmingham, UK, United Kingdom, B15 2PR
- Recruiting
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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Contact:
- Charlotte Dawson, MD
- Phone Number: 44 (0) 121 371 6983
- Email: charlotte.dawson@uhb.nhs.uk
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London, UK, United Kingdom, WC1N 3JH
- Recruiting
- Great Ormond Street Hospital For Children NHS Foundation Trust
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Contact:
- Spyros Batzios, MD
- Phone Number: +44 02074059200
- Email: spyros.batzios@gosh.nhs.uk
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 65 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARCT-810
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.
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ARCT-810 is messenger RNA (mRNA) coding for Ornithine Transcarbamylase (OTC) formulated in a lipid nanoparticle (LNP) under development.
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Placebo Comparator: Placebo, Normal Saline
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.
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Normal Saline
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence, severity and dose-relationship of adverse events (AEs)
Time Frame: Week 23
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Safety and tolerability of ARCT-810 assessed by determining the number of AEs by dose
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Week 23
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma concentration area under the curve after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point
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Up to 17 Weeks
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Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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The maximum observed plasma concentration (Cmax)
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Up to 17 Weeks
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Time at which Cmax occurred after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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The time at which Cmax occurred (Tmax)
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Up to 17 Weeks
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AUC0-inf after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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Plasma AUC from time zero extrapolated to infinity
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Up to 17 Weeks
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AUCExtrap after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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The relative portion of AUC0-inf extrapolated beyond AUC0-t
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Up to 17 Weeks
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T1/2 after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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Terminal half-life
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Up to 17 Weeks
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MRT0-inf after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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The mean residence time extrapolated to infinity
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Up to 17 Weeks
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CL after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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Total body clearance, calculated as dose divided by AUC0-inf
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Up to 17 Weeks
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Vss after first and last doses of ARCT-810
Time Frame: Up to 17 Weeks
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Volume of distribution
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Up to 17 Weeks
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Urea Cycle Function
Time Frame: Week 12
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Change from baseline in urea cycle function as measured by 13C-urea assay
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Week 12
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Plasma Ammonia
Time Frame: Week 11
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Change from baseline in urea cycle function as measured by 24-hour plasma ammonia profile
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Week 11
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 6, 2022
Primary Completion (Anticipated)
December 1, 2023
Study Completion (Anticipated)
June 1, 2024
Study Registration Dates
First Submitted
August 8, 2022
First Submitted That Met QC Criteria
August 30, 2022
First Posted (Actual)
September 2, 2022
Study Record Updates
Last Update Posted (Actual)
April 7, 2023
Last Update Submitted That Met QC Criteria
April 6, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Amino Acid Metabolism, Inborn Errors
- Urea Cycle Disorders, Inborn
- Ornithine Carbamoyltransferase Deficiency Disease
Other Study ID Numbers
- ARCT-810-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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