Adeno-associated virus serotype RH79 containing the human OTC gene for Ornithine transcarbamylase deficiency (OTC)

Inclusion criteria

• {"criterion_text":"- Male sex\n- Gestational or adjusted (corrected) gestational age ≥ 37 weeks\n- Age at screening is 24 hours to 7 months\n- Genetically confirmed OTC deficiency (OTCD) defined by the following: • Genetic confirmation of an OTC variant (pathogenic or likely pathogenic) associated with severe neonatal OTCD as defined below or has the same OTC variant as a family member who had severe neonatal OTCD within first week of life • Note: a prenatal genetic diagnosis will be confirmed post-birth and prior to dosing.\n- Severe neonatal OTCD defined by the following: • Documented hyperammonemic crisis with elevated ammonia level of >560 μmol/L and clinical symptoms that include but are not limited to lethargy, poor feeding, coma, seizure and/or other neurologic sequelae) within first week of life and currently receiving treatment with dietary protein restriction and nitrogen scavenger therapy.\n- 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. Note: This is not applicable for a participant expectantly managed.\n- Participant’s parent/legal 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 ECUR-LTFU protocol\n- Weight ≥ 3.5 kg and ≤ 13.5 kg at screening\n- Has received age-appropriate vaccinations."}

Exclusion criteria

• {"criterion_text":"- Neonatal diagnosis of severe to profound Hypoxic Ischemic Encephalopathy (based on standard HIE metrics) due to birth injury\n- Requiring urgent liver transplant due to liver failure as assessed by the principal investigator\n- Contiguous gene deletion syndrome involving the OTC gene and including at least the CYBB gene on the telomeric side or the TSPAN7 gene on the centromeric side.\n- 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 care\n- Treatment with any other gene therapy or gene editing therapy\n- Co-enrollment in any other study unless approved by the sponsor\n- Any condition, that in the opinion of the Investigator, would compromise the safety of the participant or study data\n- Documented vertical transmission of HepA/HepB/HepC\n- 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"}

Primary endpoints

• {"endpoint_text":"- Treatment-emergent adverse events (incidence, severity, seriousness, and relatedness)","definition_or_measurement_approach":"Collection and reporting of treatment-emergent adverse events including incidence, severity, seriousness and investigator-assessed relatedness (as stated in endpoint)."}
• {"endpoint_text":"- The following will be assessed as change from baseline at pre-specified timepoints as described in the Schedule of Events throughout the duration of the study. • Physical exam parameters • Vital signs • Pediatric Neurologist exam parameters • Blood safety tests including hematology, serum chemistry, liver function tests, coagulation tests • Urinalysis evaluations • 12 lead ECG parameters","definition_or_measurement_approach":"Assessments performed as change from baseline at pre-specified timepoints per the Schedule of Events throughout study duration."}
• {"endpoint_text":"- Achieving normal fasting plasma ammonia by EOS, defined as ammonia levels that fall within normal limits for at least 75% of post-dose assessments, including all unscheduled and repeat assessments.","definition_or_measurement_approach":"Fasting plasma ammonia measured at post-dose assessments; normal defined as within normal limits for ≥75% of post-dose assessments (including unscheduled/repeat assessments)."}
• {"endpoint_text":"- Complete clinical response by EOS, defined as the discontinuation of scavenger medication for a minimum duration of 28 days without reductions in prescribed daily protein intake during this time period.","definition_or_measurement_approach":"Clinical response defined by discontinuation of nitrogen scavenger medication for ≥28 days without reduction in prescribed daily protein intake; assessed through medication records and dietary intake monitoring."}

Secondary endpoints

• {"endpoint_text":"- Number of hyperammonemic crises (HAC) defined as: • Fasting plasma ammonia levels > 100 µmol/L with associated neurological status changes.","definition_or_measurement_approach":"Count of HAC events meeting definition: fasting plasma ammonia >100 µmol/L with associated neurological status changes."}
• {"endpoint_text":"- Number of HAC with the following severities: • 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","definition_or_measurement_approach":"HAC events categorised by severity as defined (mild/moderate/severe) based on required interventions."}
• {"endpoint_text":"- Vector PK in blood and shedding in urine and feces","definition_or_measurement_approach":"Measurement of vector pharmacokinetics in blood and assessment of vector shedding in urine and feces samples."}
• {"endpoint_text":"- Scavenger drug dose per body surface area (BSA)","definition_or_measurement_approach":"Recording and calculation of scavenger medication dose normalized to body surface area (BSA)."}
• {"endpoint_text":"- Protein allowance g/kg/day","definition_or_measurement_approach":"Assessment of prescribed/allowed protein intake expressed as g/kg/day."}
• {"endpoint_text":"- Blood urea nitrogen measurements","definition_or_measurement_approach":"Laboratory measurement of blood urea nitrogen (BUN) at scheduled timepoints."}
• {"endpoint_text":"- Fasting plasma ammonia","definition_or_measurement_approach":"Fasting plasma ammonia measured at scheduled assessments."}
• {"endpoint_text":"- Achieving and maintaining through EOS complete clinical response and normal fasting plasma ammonia levels (defined as in primary endpoint) following the discontinuation of nitrogen scavenger medications.","definition_or_measurement_approach":"Composite assessment of clinical response and maintenance of normal fasting plasma ammonia after discontinuation of nitrogen scavenger medications, using the same definitions as primary endpoints."}

Spain

Earliest CTIS Part Ii Submission Date

06-08-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

612

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Iecure Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Labcorp Central Laboratory Services S.a.r.l.

Responsibilities

sponsorDuties codes: [4]

Name

Fortrea Inc.

Responsibilities

sponsorDuties codes: [1,12,15,2,5,6,7]; includes: Regulatory, ethics and third body submissions; clinical ancillary supply management

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties codes: [1,12,15,2,5,6,7]; includes role text: 'Regulatory, ethics and third body submissions; clinical ancillary supply management'","organisation_type":"Pharmaceutical company"}