A Phase I/II/III 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
Ornithine Transcarbamylase (OTC) Deficiency
Cohort 1 - Participants will receive the Low Dose of ECUR-506 delivered one time via IV Infusion. Cohort 2 - Participants will receive the High Dose of ECUR-506 delivered one time via IV infusion Expansion Cohort - Participants will receive ECUR-506 at one of the doses evaluated in Cohort 1 or Cohort 2 one time via IV infusion.
1. Male sex 2. Gestational age ≥ 37 weeks 3. Age at screening is 24 hours to 7 months 4. Genetically confirmed OTC deficiency (OTCD). Documented analysis either through prenatal testing or post-birth genetic testing. Note: a prenatal testing diagnosis will be confirmed post-birth and prior to dosing. 5. Severe neonatal OTCD defined by the following: 5.1. Current or past hyperammonemic crisis (which includes but is not limited to: severely elevated [>8 x ULN] ammonia levels, lethargy, poor feeding, coma, seizure) within first week of life OR 5.2. Family history and genetic confirmation of pathogenic or likely pathogenic variant consistent with severe OTCD, or has same genetic mutation as previous family member who had severe disease with neonatal onset within first week of life AND 5.3. Currently receiving treatment (e.g., dietary and scavenger therapy) 6. In participants not prenatally diagnosed, current or historical (within 2 weeks prior to Screening) biochemical profile consistent with OTCD: below LLN of plasma citrulline/arginine and urine orotic aciduria at time of diagnosis 7. Participant’s parents/legally authorized representative must be able to comprehend and be willing to provide a signed IRB/IEC-approved ICF which will include consent for participation in this 24 week protocol with immediate roll-over into the 14.5 year long term follow-up (ECUR-LTFU) study.
1. Neonatal diagnosis of severe to profound Hypoxic Ischemic Encephalopathy (based on standard HIE metrics) 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 (brain, heart, liver, kidneys) other than what is consistent with OTCD, based on routine medical assessments performed as part of standard of care 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 protocol 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