An open-label study to investigate ECUR-506 in male children less than 9 months of age with neonatal onset OTC deficiency

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Iecure Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

10 Apr 2026 → ongoing

Decision date (initial)

2024-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

iECURE Inc

External identifiers

EU CT number

2023-506180-34-01

ClinicalTrials.gov

NCT06255782

ISRCTN

ISRCTN10957794

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Therapy, Dose response

To assess the safety, tolerability and efficacy of up to three dose levels of ECUR-506 following IV administration of a single dose.

Secondary objectives 1

1. To assess the pharmacokinetics (PK) and further assess the efficacy of up to three dose levels of ECUR-506 following IV administration of a single dose.

Conditions and MedDRA coding

Ornithine Transcarbamylase Deficiency (OTC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

The Spanish Agency Of Medicines And Medical Devices

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male sex
2. Gestational or adjusted (corrected) gestational age ≥ 37 weeks
3. Age at screening is 24 hours to 7 months
4. 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.
5. 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.
6. 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.
7. 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
8. Weight ≥ 3.5 kg and ≤ 13.5 kg at screening
9. Has received age-appropriate vaccinations.

Exclusion criteria 9

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 principal investigator
3. 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.
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 care
5. Treatment with any other gene therapy or gene editing therapy
6. Co-enrollment in any other study unless approved by the sponsor
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 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Treatment-emergent adverse events (incidence, severity, seriousness, and relatedness)
2. 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
3. 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.
4. 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.

Secondary endpoints 8

1. Number of hyperammonemic crises (HAC) defined as: • Fasting plasma ammonia levels > 100 µmol/L with associated neurological status changes.
2. 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
3. Vector PK in blood and shedding in urine and feces
4. Scavenger drug dose per body surface area (BSA)
5. Protein allowance g/kg/day
6. Blood urea nitrogen measurements
7. Fasting plasma ammonia
8. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Iecure Inc.

Sponsor organisation

Iecure Inc.

Address

1777 Sentry Parkway West Suite 200 Building 14

City

Blue Bell

Postcode

19422-2211

Country

United States

Scientific contact point

Organisation

Iecure Inc.

Contact name

Therapeutic Area Lead - Urea Cycle Disorders

Public contact point

Organisation

Iecure Inc.

Contact name

iECURE - Regulatory Affairs

Third parties 2

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications