An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC Deficiency (OTC-HOPE)

Phase 1

Recruiting

• Conditions: Ornithine Carbamoyltransferase Deficiency (Disorder); Ornithine Transcarbamylase Deficiency; Ornithine Transcarbamylase Deficiency Disease; Urea Cycle Disorders, Inborn
• Interventions: Genetic: ECUR-506

• Registration Number: NCT06255782
• Lead Sponsor: iECURE, Inc.

Brief Summary

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 detoxification of ammonia. Individuals with OTC deficiency can build-up excess levels of ammonia in their blood, potentially resulting in devastating consequences, including cumulative and irreversible neurological damage, coma and death. The severe form of the condition emerges shortly after birth and is more common in boys than girls.

This is a Phase 1/2, open-label, multicenter, safety and dose finding study of ECUR-506 in male babies with neonatal onset OTC deficiency. The primary objective of this study is to evaluate the safety and tolerability of multiple dose levels of ECUR-506 following intravenous (IV) administration of a single dose.

Detailed Description

The study drug, ECUR-506, is an investigational gene editing therapy. Gene editing is a way to repair, replace, or introduce new copies of genes that don't work. The study drug contains a working copy of the OTC gene that will be delivered by an IV infusion. It also contains a gene to encode the editing enzyme which is the part of the study drug that can cut DNA so that the OTC gene can be inserted. The study drug was designed to introduce a working copy of the OTC gene and a gene to encode the editing enzyme. A gene cannot enter cells by itself, it needs a delivery mechanism to move the gene into the cells. In this study, a commonly used virus called adeno-associated virus (AAV) is used to enter the cells and deliver the genes.

Study Timeline

• Study First Submitted: 2023-12-19
• Study First Submitted QC: 2024-02-02
• Study First Posted: 2024-02-13
• Study Start: 2024-04-08
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-13
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 13

Inclusion Criteria

1. Male sex
2. Gestational age ≥ 37 weeks
3. Age at screening is 24 hours to 7 months*
4. Weight ≥ 3.5 kg and ≤ 10.0 at screening
5. Has received all age-appropriate vaccinations
6. Genetically confirmed OTCD
7. Severe neonatal OTCD defined by hyperammonemic crisis within first week of life
8. Current or historical biochemical profile consistent with OTCD
9. Participant's parent(s)/LAR must be able to comprehend and be willing to provide a signed IRB/IEC-approved ICF.

Key

Exclusion Criteria

1. Neonatal diagnosis of severe to profound Hypoxic Ischemic Encephalopathy due to birth injury
2. Requiring urgent liver transplant due to liver failure as assessed by the PI.
3. Contiguous gene deletion involving the OTC gene
4. Known or suspected major organ injury/dysfunction/anomalies.
5. Treatment with any other gene therapy or gene editing therapy
6. Co-enrollment in any other clinical study with an investigational product prior to or during the duration of this trial would require the participant to be withdrawn from this study
7. Any condition, that in the opinion of the Investigator, would compromise the safety of the participant or study data
8. Documented vertical transmission of HSV, HIV, or HepA/HepB/HepC
9. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Additional Cohorts	ECUR-506	Additional Cohorts based on recommendations of DMC review of safety and efficacy data.
Cohort 2	ECUR-506	Participants will receive a higher dose of ECUR-506 delivered one time via IV infusion.
Cohort 1	ECUR-506	Participants will receive the Low Dose of ECUR-506 delivered one time via IV Infusion.

Primary Outcome Measures

Name	Time	Method
Treatment-emergent adverse events (incidence, severity, seriousness, and relatedness)	Over 24 weeks post infusion	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.
Urinalysis evaluations	Assessed as change from baseline at pre-specified timepoints through Week 24 post infusion.	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.

Secondary Outcome Measures

Name	Time	Method
Scavenger drug dose per body surface area (BSA)	Over 24 weeks post infusion	Efficacy
Percent liver transduction	Assessed at Week 24	Pharmacokinetics
Number of hyperammonemic crises (HAC)	Over 24 weeks post infusion	Pharmacodynamics and Efficacy
qPCR measurement to evaluate the clearance of both vectors in body fluids over time	Over 24 weeks post infusion	Pharmacokinetics
Protein allowance g/kg	Over 24 weeks post infusion	Efficacy
Blood urea nitrogen measurements	Over 24 weeks post infusion	Pharmacodynamics

Trial Locations

Locations (8)

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

UCLA Mattel Children's Hospital; 🇺🇸 Los Angeles, California, United States

Children's Hospital of Colorado, Anshutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

The Children's Hospital at Westmead; 🇦🇺 Sydney, New South Wales, Australia

Hopsital Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust- Great North Children's Hospital; 🇬🇧 Newcastle Upon Tyne, United Kingdom