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 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 1/2/3, open-label, multicenter, safety, efficacy, 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, tolerability, and efficacy of up to three dose levels of ECUR-506 following intravenous (IV) administration of a single dose.

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

7. Severe neonatal OTCD defined by hyperammonemic crisis with elevated ammonia level of >560 μmol/L and clinical symptoms 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 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 abnormalities

6. Laboratory abnormalities outside of laboratory normal ranges for urinalysis, complete blood count, and comprehensive metabolic panel that are attributable to comorbidities unrelated to OTCD

7. Treatment with any other gene therapy or gene editing therapy

8. Co-enrollment in any other clinical study unless approved by the sponsor.

9. Any condition, that in the opinion of the Investigator, would compromise the safety of the participant or study data

10. Documented vertical transmission of HepA/HepB/HepC

11. 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

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