An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC Deficiency
Ornithine Transcarbamylase (OTC) deficiency, the most common urea cycle disorder, is an inherited metabolic disorder caused by a genetic defect in a liver enzyme responsible for detoxifying of ammonia. Individuals with OTC deficiency can develop elevated levels of ammonia in the blood, potentially resulting in severe consequences, including cumulative and irreversible neurological damage, coma, and death. The most severe form presents shortly after birth and occurs more commonly in boys than girls.
This is a Phase 1/2/3, open-label, multicenter study evaluating the safety, efficacy, and dose of ECUR-506 in male babies with neonatal-onset OTC deficiency. The primary objective is to evaluate the safety, tolerability, and efficacy of up to three dose levels of ECUR-506 following intravenous (IV) administration of a single dose.
Study details:
The study drug, ECUR-506, is an investigational gene editing therapy. Gene editing is an approach used to repair, replace, or introduce functional copies of genes that are not working properly. ECUR-506 contains a functional copy of the OTC gene, along with a gene to encode an editing enzyme that enables insertion of the OTC gene into the genome.
The study drug is administered as a single IV infusion. Because genes cannot enter cells on their own, ECUR-506 uses a delivery system based on adeno-associated virus (AAV), a commonly used viral vector, to transport the genetic material into cells.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Male sex
- Gestational or adjusted (corrected) gestational age ≥ 37 weeks
- Age at screening is 24 hours to 7 months
- Weight ≥ 3.5 kg and ≤ 13.5 kg at screening
- Has received age-appropriate vaccinations
- Genetically confirmed OTCD
- Severe neonatal OTCD defined by hyperammonemic crisis with elevated ammonia level of >560 μmol/L and clinical symptoms within first week of life
- Current or historical biochemical profile consistent with OTCD
- Participant's parent(s)/LAR must be able to comprehend and be willing to provide a signed IRB/IEC-approved ICF
Exclusion criteria
- Neonatal diagnosis of severe to profound Hypoxic Ischemic Encephalopathy due to birth injury
- Requiring urgent liver transplant due to liver failure as assessed by the PI.
- Contiguous gene deletion involving the OTC gene and including at least the CYBB gene on the telomeric side or the TSPAN7 gene on the centromeric side.
- Known or suspected major organ injury/dysfunction/anomalies.
- Vital sign abnormalities
- Laboratory abnormalities outside of laboratory normal ranges for urinalysis, complete blood count, and comprehensive metabolic panel that are attributable to comorbidities unrelated to OTCD
- Treatment with any other gene therapy or gene editing therapy
- Co-enrollment in any other clinical study unless approved by the sponsor.
- Any condition, that in the opinion of the Investigator, would compromise the safety of the participant or study data
- Documented vertical transmission of HepA/HepB/HepC
- Documented in-utero teratogen, substance, and/or alcohol exposure, which in the opinion of the Investigator may increase the participant's risk of developmental delays, congenital anomalies, and/or significant medical complications
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: MALE
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06255782
Intervention or treatment
GENETIC: ECUR-506
Conditions
- Ornithine Transcarbamylase Deficiency
- Ornithine Transcarbamylase Deficiency Disease
- Ornithine Carbamoyltransferase Deficiency (Disorder)
- Urea Cycle Disorders, Inborn
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
The Children's Hospital at Westmead
Select from list below to view details:
The Children's Hospital at Westmead
Sydney, New South Wales, Australia
The Royal Children's Hospital
Melbourne, Victoria, Australia
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Who is running the clinical trial?
iECURE, Inc.
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?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Low Dose Level
| Genetic: ECUR-506 |
EXPERIMENTAL: Intermediate Dose Level
| Genetic: ECUR-506 |
EXPERIMENTAL: High Dose Level
| Genetic: ECUR-506 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-emergent adverse events (incidence, severity, seriousness, and relatedness) | Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Adverse events (AEs) are reported based on clinical laboratory tests, vital signs, physical examinations, Pediatric Neurologist exam parameters, electrocardiograms, and any other medically indicated assessments from the time informed consent is signed through the end of the safety follow-up period. AEs are considered to be treatment emergent (TEAE) if they occur or worsen in severity following the administration of the study treatment. TEAEs are considered treatment-related if relationship to study drug is possibly related, probably related, or definitely related. | Over 24 weeks post infusion |
| Urinalysis evaluations | Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Adverse events (AEs) are reported based on clinical laboratory tests, vital signs, physical examinations, electrocardiograms, and any other medically indicated assessments from the time informed consent is signed through the end of the safety follow-up period. AEs are considered to be treatment emergent (TEAE) if they occur or worsen in severity following the administration of the study treatment. TEAEs are considered treatment-related if relationship to study drug is possibly related, probably related, or definitely related. | Assessed as change from baseline at pre-specified timepoints through Week 24 post infusion. |
| Achieving normal fasting plasma ammonia levels by EOS | Fasting plasma ammonia levels that fall within normal limits for at least 75% of post-dose assessments. | Over 24 weeks post infusion |
| Complete clinical response | Discontinuation of scavenger medication for a minimum duration of 28 days without reductions in prescribed daily protein intake during this time period. | Over 24 weeks post infusion |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Percent liver transduction | Pharmacokinetics | Assessed at Week 24 |
| Number of hyperammonemic crises (HAC) | Pharmacodynamics and Efficacy | Over 24 weeks post infusion |
| qPCR measurement to evaluate the clearance of both vectors in body fluids over time | Pharmacokinetics | Over 24 weeks post infusion |
| Scavenger drug dose per body surface area (BSA) | Efficacy | Over 24 weeks post infusion |
| Protein allowance g/kg/day | Efficacy | Over 24 weeks post infusion |
| Blood urea nitrogen measurements | Pharmacodynamics | Over 24 weeks post infusion |
| Fasting plasma ammonia | Efficacy | Over 24 weeks post infusion |
References
Clinical Trials Gov: An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC DeficiencyOther trials to consider
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