Gene therapy for male infants with a severe metabolic disorder

A Phase 1/2/3 First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of a Single Intravenous (IV) Administration of ECUR-506 in Males Less Than 9 Months of Age With Genetically Confirmed Neonatal Onset Ornithine Transcarbamylase (OTC) Deficiency

This study is testing a new gene therapy for baby boys with a serious metabolic disorder to see if it can safely provide them with a working copy of a missing gene.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 24 Hours to 7 Months
• Sex: Male
• Sponsor: iECURE, Inc. (Industry-sponsored)
• Locations: 12 sites (Los Angeles, California and 11 other locations)
• Trial ID: NCT06255782 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter study investigates the safety and tolerability of ECUR-506, a gene editing therapy, in male infants under 9 months old diagnosed with neonatal onset Ornithine Transcarbamylase (OTC) deficiency. The therapy aims to deliver a functional copy of the OTC gene using an adeno-associated virus (AAV) as a delivery mechanism. Participants will receive intravenous infusions of the study drug, and the study will assess multiple dose levels to determine the optimal dosing strategy.

Who should consider this trial

Good fit: Ideal candidates are male infants aged 24 hours to 7 months with genetically confirmed severe neonatal OTC deficiency.

Not a fit: Patients with severe to profound Hypoxic Ischemic Encephalopathy or those requiring urgent liver transplant will not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly reduce ammonia levels in affected infants, potentially preventing neurological damage and improving long-term outcomes.

How similar studies have performed: While gene therapy approaches for metabolic disorders are emerging, this specific application of gene editing for OTC deficiency is novel and has not been extensively tested in prior studies.

Eligibility criteria

Key Inclusion Criteria:

1. Male sex
2. Gestational or adjusted (corrected) gestational age ≥ 37 weeks
3. Age at screening is 24 hours to 7 months
4. Weight ≥ 3.5 kg and ≤ 13.5 kg at screening
5. Has received age-appropriate vaccinations
6. Genetically confirmed OTCD defined by genetic confirmation of an OTC variant (pathogenic or likely pathogenic) associated with severe neonatal OTCD defined below in Inclusion Criteria #7 or has the same OTC variant as a family member who had severe neonatal OTCD within first week of life.
7. 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.
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 and including at least the CYBB gene on the telomeric side or the TSPAN7 gene on the centromeric side.
4. Known or suspected major organ injury/dysfunction/anomalies.
5. Vital sign and laboratory abnormalities outside of reference ranges.
6. Treatment with any other gene therapy or gene editing therapy
7. Co-enrollment in any other study unless approved by the sponsor.
8. Any condition, that in the opinion of the Investigator, would compromise the safety of the participant or study data
9. Documented vertical transmission of HepA/HepB/HepC
10. 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

Where this trial is running

Los Angeles, California and 11 other locations

• UCLA Mattel Children's Hospital — Los Angeles, California, United States (Recruiting)
• Children's Hospital of Colorado, Anshutz Medical Campus — Aurora, Colorado, United States (Recruiting)
• Emory University School of Medicine — Atlanta, Georgia, United States (Recruiting)
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (Recruiting)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
• Oregon Health and Science University — Portland, Oregon, United States (Recruiting)
• The Children's Hospital at Westmead — Sydney, New South Wales, Australia (Active_not_recruiting)
• The Royal Children's Hospital — Melbourne, Victoria, Australia (Active_not_recruiting)
• Hopsital Sant Joan de Deu — Barcelona, Spain (Recruiting)
• Hospital Universitario 12 de Octubre — Madrid, 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)

Study contacts

• Study coordinator: George Diaz, M.D., Ph.D.

Conditions Ornithine Transcarbamylase Deficiency; Ornithine Transcarbamylase Deficiency Disease; Ornithine Carbamoyltransferase Deficiency; Urea Cycle Disorders, Inborn; Amino Acid Metabolism, Inborn Errors; Ammonia; Brain Diseases; Brain Diseases, Metabolic