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

NCT06255782 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ECUR-506-OTC-101OTC-HOPE
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 12

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 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.

Conditions

Ornithine Transcarbamylase Deficiency Disease; Urea Cycle Disorders, Inborn; Ornithine Transcarbamylase Deficiency; Ornithine Carbamoyltransferase Deficiency (Disorder)

Keywords

Amino Acid Metabolism, Inborn Errors; Ammonia; Brain Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Central Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; High Ammonia; Hyperammonemia; Inborn; Inborn Errors; Inherited Metabolic Disorders; Liver Disease; Liver Transplant; Metabolism; Metabolic Diseases; Metabolism, Inborn Errors; Neonatal; Nervous System Diseases; Neurometabolic disorders; NH4; Ornithine; Ornithine Transcarbamylase Deficiency; OTC; OTC Deficiency; OTCD; Transcarbamylase; UCD; Urea Cycle Disorders; X-Linked

Outcome Measures

Primary Outcomes (8)

• 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

• Physical exam parameters

  Safety- (Includes PI assessment of General Appearance, Dermatological, HEENT, Lymphatic, Respiratory, Cardiovascular, Gastrointestinal, Musculoskeletal, Neurological (Cranial Nerve Function, Motor System Function, Sensory System Function, Primitive Reflexes))

  Assessed as change from baseline at pre-specified timepoints as described in the SOE throughout the duration of the study on all enrolled and dosed participants.

• Vital sign parameters

  Safety- (Includes PI assessment of Systolic Blood Pressure, Diastolic Blood Pressure, Pulse Rate, Respiratory Rate, Temperature)

  Assessed as change from baseline at pre-specified timepoints as described in the SOE throughout the duration of the study on all enrolled and dosed participants.

• Pediatric neurologist exam parameters

  Safety- (Includes Pediatric Neurologist assessment of Neurological status by review of Cranial Nerve Function, Motor System Function, Sensory System Function, Primitive Reflexes.)

  Assessed as change from baseline at pre-specified timepoints as described in the SOE throughout the duration of the study on all enrolled and dosed participants.

• Blood safety tests including hematology, serum chemistry, liver function tests, coagulation tests

  Safety- (Blood Safety tests to be reviewed in relation to established normal ranges for each assessment for the applicable age group)

  as change from baseline at pre-specified timepoints as described in the SOE throughout the duration of the study on all enrolled and dosed participants.

• 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.

• 12 lead ECG parameters

  Safety- (Includes PI review of Heart Rate, PR Interval, RR Interval, QRS Duration, QT Interval, QTcF Interval, Overall Interpretation)

  as change from baseline at pre-specified timepoints as described in the SOE throughout the duration of the study on all enrolled and dosed participants.

• 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 by end of study.

  Over 24 weeks post infusion

Secondary Outcomes (14)

• Number of HAEs/person-year

  Day 1 post dose through Week 24

• qPCR measurement to evaluate the clearance of both vectors in body fluids over time

  Over 24 weeks post infusion

• Incidence of hyperammonemic episode (HAE)

  Over 24 weeks post infusion

• Incidence and number of hyperammonemic episodes (HAE/HAC) resulting in hospitalization

  Over 24 weeks post infusion

• Overall and by hospitalization severity (Mild: adjustment of dietary protein intake and oral scavenger medication / Moderate: cessation of dietary protein intake and initiation of IV scavenger therapy / Severe: requirement for hemodialysis)

  Will be assessed Day 1 post dose through Wk 24 on all enrolled and dosed participants

Other Outcomes (21)

• Clinical Response (CR) defined as reduction in baseline standard of care therapy

  Assessed at Week 24

• Serum Neurofilament Light Chain

  Assessed as change from baseline at pre-specified timepoints through Week 24 post infusion.

• Number of participants with antibodies to AAVrh79 capsid in blood

  Assessed as change from baseline at pre-specified timepoints through Week 24 post infusion.

Study Arms (3)

Low Dose Level

EXPERIMENTAL

Participants will receive the Low Dose of ECUR-506 delivered one time via IV Infusion.

Genetic: ECUR-506

Intermediate Dose Level

EXPERIMENTAL

Participants will receive an intermediate dose of ECUR-506 delivered on time via IV infusion

Genetic: ECUR-506

High Dose Level

EXPERIMENTAL

Participants will receive a higher dose of ECUR-506 delivered one time via IV infusion.

Genetic: ECUR-506

Interventions

ECUR-506 GENETIC

ECUR-506 is a gene editing treatment delivering a gene encoding the editing enzyme and an OTC gene.

High Dose Level; Intermediate Dose Level; Low Dose Level

Eligibility Criteria

• Age: 24 Hours - 7 Months
• Gender Eligibility Details: Males present with the highest unmet medical need, and in order to reduce the variability of the study population, participants are restricted to the male sex. OTC is primarily inherited in an X-linked recessive pattern, meaning that it mostly affects males, who only have one copy of the X chromosome. Females, who have two X chromosomes, can be carriers of the condition. Some females may experience milder OTC symptoms, or they may have no symptoms.
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• Severe neonatal OTCD defined by hyperammonemic crisis with elevated ammonia level of \>560 μmol/L and clinical symptoms within first week of life, and currently receiving treatment with both dietary protein restriction and nitrogen scavenger therapy.
• 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.

You may not qualify if:

• 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 and laboratory abnormalities outside of reference ranges.
• Treatment with any other gene therapy or gene editing therapy
• Co-enrollment in any other 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

Sponsors & Collaborators

• iECURE, Inc.: lead

Study Sites (12)

UCLA Mattel Children's Hospital

Los Angeles, California, 90095, United States

RECRUITING

Children's Hospital of Colorado, Anshutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

The Children's Hospital at Westmead

Sydney, New South Wales, Australia

ACTIVE NOT RECRUITING

The Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

ACTIVE NOT RECRUITING

Hopsital Sant Joan de Deu

Barcelona, 08950, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Great Ormond Street Hospital

London, United Kingdom

RECRUITING

The Newcastle upon Tyne Hospitals NHS Foundation Trust- Great North Children's Hospital

Newcastle upon Tyne, United Kingdom

RECRUITING

MeSH Terms

Conditions

Ornithine Carbamoyltransferase Deficiency Disease; Urea Cycle Disorders, Inborn; Amino Acid Metabolism, Inborn Errors; Brain Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Central Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Hyperammonemia; Liver Diseases; Metabolic Diseases; Metabolism, Inborn Errors; Nervous System Diseases

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Diseases

Study Officials

• George Diaz, M.D., Ph.D

  iECURE, Inc.

  STUDY DIRECTOR

Central Study Contacts

George Diaz, M.D., Ph.D.

CONTACT

1-877-694-3558; medinfo@iecure.com

Trial Recruitment

CONTACT

clinicaltrials@iecure.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation with dose staggering. Dose selection will be based on an assessment of the totality of the safety and efficacy.

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: February 13, 2024
• Study Start: April 8, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); AU (2); ES (2); GB (2)