Ornithine Transcarbamylase DeficiencyPhase 1NCT04442347
Phase 1b Study to Assess Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency
A Phase 1 study testing ARCT-810 in people with Ornithine Transcarbamylase Deficiency, run by Arcturus Therapeutics, Inc. at 8 sites in United States.
Trial summary
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia scavengers) with ornithine transcarbamylase deficiency (OTCD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ornithine Transcarbamylase Deficiency
- What is being tested?
- ARCT-810
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 8 sitesUnited States
- Study dates
- 3 Nov 2020to 30 Apr 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adequate cognitive ability to consent and recall symptoms over a 1-week time period
- Males and females ≥18 years of age with documented diagnosis of ornithine transcarbamylase deficiency (OTCD) confirmed with genetic testing, or willing to consent to OTC gene sequencing and deletion/duplication testing
- Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by
- no clinical symptoms of hyperammonemia AND
- an ammonia level <100 µmol/L (170 µg/dL) at the screening evaluation
- Subjects must remain free from symptoms of hyperammonemia throughout the screening period.
Show all 12Show fewer
- If using nitrogen ammonia scavenger therapy, must be on a stable regimen (no change in dose or frequency) for ≥ 28 days prior to providing informed consent and throughout the screening period
- Must have maintained a stable protein-restricted diet (+/- amino acid supplementation) for at least 28 days prior to providing informed consent and continue to maintain a stable diet for the duration of the study
- Good general health other than OTCD, in the opinion of the Investigator
- Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before study visits
- Willingness to comply with procedures and visits
- Willingness to follow contraception guidelines
Who cannot join
- History of clinically significant disease(s), in the opinion of the Investigator
- Clinically significant screening laboratory values
- Uncontrolled diabetes
- Clinically significant anemia
- Subjects who develop infection during screening must be asymptomatic for at least 7 days prior to dosing
- Unwillingness to comply with study requirements
Show all 19Show fewer
- History of positive HIV, hepatitis C, or chronic hepatitis B
- Uncontrolled hypertension
- Malignancy within 5 years prior to study
- Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug
- Treatment with any oligonucleotide or mRNA within 6 months of screening, with exceptions for some vaccinations and investigational treatments
- History of gene therapy, hepatocyte or mesenchymal stem cell transplantation
- Prior organ transplant
- History of severe allergic reaction to a liposomal product
- Recent history of, or current, drug or alcohol abuse
- Dependence on inhaled (smoked or vaped) or oral cannabis products
- Systemic corticosteroids within 6 weeks prior to screening
- Blood donation of 50 to 499 mL within 30 days of screening or of .499 mL within 60 days of screening
- Other conditions, in the opinion of the Investigator, that would make the subject unsuitable for participation
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
University of Florida
Gainesville, Florida, 32608
Children's Wisconsin - Milwaukee Hospital
Milwaukee, Wisconsin, 53226
M Health Fairview Masonic Children's Hospital
Minneapolis, Minnesota, 55454
The Mount Sinai Hospital
New York, New York, 10029
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of Utah
Salt Lake City, Utah, 84112
Baylor University
Waco, Texas, 76706
About this study
Official title: A Phase 1b Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Clinically Stable Patients With Ornithine Transcarbamylase Deficiency
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia scavengers) with ornithine transcarbamylase deficiency (OTCD).
Read the detailed description
This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum of 20) clinically stable patients with ornithine transcarbamylase deficiency (OTCD) are planned to be enrolled.
Each study subject's participation length is approximately 8 weeks, from screening through last study visit. The study comprises an up to 4-week screening period, and a 4-week diet run-in period, to occur concurrently, followed by a 1-day dosing period and a 28-day post-treatment period.
Study participants will be allocated to one of the three single-dose treatment groups (also referred to as cohorts), to test different doses of ARCT-810. Four subjects will be enrolled in each group. Within each cohort, subjects will be randomized 3:1 to receive ARCT-810 or placebo as an IV infusion.
- Conditions
- Ornithine Transcarbamylase Deficiency
- Being tested
- ARCT-810, Placebo
- Medical subject headings
- Ornithine Carbamoyltransferase Deficiency Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARCT-810Biological
ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) mRNA formulated in a lipid nanoparticle (LNP) under development.
PlaceboOther
The placebo for this study is 0.9% sterile saline.
| Study group | Role | What they receive |
|---|---|---|
| ARCT-810 | Experimental | Ascending single doses of ARCT-810 administered intravenously Receives: Biological: ARCT-810 |
| Placebo | Placebo comparator | Single doses of 0.9% Saline administered intravenously Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence, severity and dose-relationship of adverse events (AEs)
Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose
Measured: 4 weeks
Secondary outcomes (9)
Change in area under the curve after single dose of ARCT-810
Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point
Measured: Up to 4 weeks
Maximum observed plasma concentration (Cmax) after single dose of ARCT-810
The maximum observed plasma concentration (Cmax)
Measured: Up to 4 weeks
Time at which Cmax occurred after single dose of ARCT-810
The time at which Cmax occurred (Tmax)
Measured: Up to 4 weeks
AUC0-inf after single dose of ARCT-810
AUC from time zero extrapolated to infinity
Measured: Up to 4 weeks
AUCExtrap after single dose of ARCT-810
The relative portion of AUC0-inf extrapolated beyond AUC0-t
Measured: Up to 4 weeks
T1/2 after single dose of ARCT-810
Terminal half-life
Measured: Up to 4 weeks
MRT0-inf after single dose of ARCT-810
The mean residence time extrapolated to infinity
Measured: Up to 4 weeks
CL after single dose of ARCT-810
Total body clearance, calculated as dose divided by AUC0-inf
Measured: Up to 4 weeks
Vss after single dose of ARCT-810
Volume of distribution
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2020
- Study start3 Nov 2020
- Primary completion30 Aug 2023
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ornithine Transcarbamylase DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arcturus Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04442347
- Sponsor's protocol ID
- ARCT-810-02
- Status last verified
- Jul 2024
- First submitted
- 19 Jun 2020
- Last updated
- 2 Aug 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Clinically Stable Patients With Ornithine Transcarbamylase Deficiency
- ClinicalTrials.gov ID
- NCT04442347
- Acronym / sponsor ID
- ARCT-810-02
- Conditions
- Ornithine Transcarbamylase Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Arcturus Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Nov 2020 (actual)
- Primary completion
- 30 Aug 2023 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 22 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia scavengers) with ornithine transcarbamylase deficiency (OTCD).
Detailed description
This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum of 20) clinically stable patients with ornithine transcarbamylase deficiency (OTCD) are planned to be enrolled.
Each study subject's participation length is approximately 8 weeks, from screening through last study visit. The study comprises an up to 4-week screening period, and a 4-week diet run-in period, to occur concurrently, followed by a 1-day dosing period and a 28-day post-treatment period.
Study participants will be allocated to one of the three single-dose treatment groups (also referred to as cohorts), to test different doses of ARCT-810. Four subjects will be enrolled in each group. Within each cohort, subjects will be randomized 3:1 to receive ARCT-810 or placebo as an IV infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARCT-810 | Experimental | Biological: ARCT-810Ascending single doses of ARCT-810 administered intravenously |
| Placebo | Placebo comparator | Other: PlaceboSingle doses of 0.9% Saline administered intravenously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adequate cognitive ability to consent and recall symptoms over a 1-week time period
- Males and females ≥18 years of age with documented diagnosis of ornithine transcarbamylase deficiency (OTCD) confirmed with genetic testing, or willing to consent to OTC gene sequencing and deletion/duplication testing
- Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by
- Subjects must remain free from symptoms of hyperammonemia throughout the screening period.
- If using nitrogen ammonia scavenger therapy, must be on a stable regimen (no change in dose or frequency) for ≥ 28 days prior to providing informed consent and throughout the screening period
Key exclusion criteria (19 listed)
- History of clinically significant disease(s), in the opinion of the Investigator
- Clinically significant screening laboratory values
- Uncontrolled diabetes
- Clinically significant anemia
- Subjects who develop infection during screening must be asymptomatic for at least 7 days prior to dosing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARCT-810ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) mRNA formulated in a lipid nanoparticle (LNP) under development. | Biological | ARCT-810 |
| PlaceboThe placebo for this study is 0.9% sterile saline. | Other | Placebo |
Primary outcome
Incidence, severity and dose-relationship of adverse events (AEs)
Time frame: 4 weeks
Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose
9 secondary outcomes
Change in area under the curve after single dose of ARCT-810
Time frame: Up to 4 weeks
Maximum observed plasma concentration (Cmax) after single dose of ARCT-810
Time frame: Up to 4 weeks
Time at which Cmax occurred after single dose of ARCT-810
Time frame: Up to 4 weeks
AUC0-inf after single dose of ARCT-810
Time frame: Up to 4 weeks
AUCExtrap after single dose of ARCT-810
Time frame: Up to 4 weeks
T1/2 after single dose of ARCT-810
Time frame: Up to 4 weeks
MRT0-inf after single dose of ARCT-810
Time frame: Up to 4 weeks
CL after single dose of ARCT-810
Time frame: Up to 4 weeks
Vss after single dose of ARCT-810
Time frame: Up to 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2024.
Related trials for Ornithine Transcarbamylase Deficiency
RecruitingObservational study
Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease
RecruitingObservational study
Abbott Vascular Medical Device Registry
Acute Myocardial Infarction, Restenoses, Coronary
RecruitingPhase 1/2
Phase 1/2 Study of KRRO-121 in Healthy Volunteers and Patients With UCD
Urea Cycle Disorders, Inborn, Urea Cycle Disorders
Active, not recruitingPhase 3
An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC Deficiency
Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease
Active, not recruitingPhase 3
Clinical Study of DTX301 AAV-Mediated Gene Transfer for Ornithine Transcarbamylase (OTC) Deficiency
OTC Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARCT-810 in people with Ornithine Transcarbamylase Deficiency, run by Arcturus Therapeutics, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence, severity and dose-relationship of adverse events (AEs) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.