ECUR-506 in Neonatal OTC Deficiency Phase I/II
- Conditions
- Ornithine Transcarbamylase (OTC) DeficiencyGenetic Diseases
- Registration Number
- ISRCTN10957794
- Lead Sponsor
- Fortrea Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- Male
- Target Recruitment
- 13
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with an investigational product prior to or during the duration of this protocol would require the participant to be withdrawn from this study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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Treatment-emergent adverse events (incidence, severity, seriousness, and relatedness)<br><br>The following will be assessed as change from last value available pre-dose at pre-specified timepoints as described in the Schedule of Events throughout the duration of the study:<br>2. Physical exam parameters<br>3. Vital signs<br>4. Neurologic exam parameters<br>5. Blood safety tests including hematology, serum chemistry, liver function tests, coagulation tests <br>6. Urinalysis evaluations<br>7. ECG parameters<br>
- Secondary Outcome Measures
Name Time Method 1.Percent liver transduction at Week 24<br>2.Number of HAC (defined as ammonia levels > 100 µmol/L and neurological status<br>3.changes) from Day 1 post dose through Week 24, overall and by severity<br>4.Vector PK in blood and shedding in urine and feces at all scheduled time points from Day1 post dose through Week 24<br>5.Scavenger drug dose per BSA from Day 1 post dose through Week 24<br>6.Protein allowance (gm/kg) from Day 1 post dose through Week 24<br>7.Blood urea nitrogen at all scheduled time points from Day 1 post dose through Week 24<br>