Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)

Recruiting

• Conditions: Ornithine Transcarbamylase Deficiency; Ornithine Transcarbamylase Deficiency Disease; Urea Cycle Disorders, Inborn

• Registration Number: NCT06805695
• Lead Sponsor: iECURE, Inc.

Brief Summary

This LTFU is being conducted to assess long-term safety and durability of response in participants dosed with IP in a parent protocol, and to collect longitudinal natural history in enrolled but not dosed participants who also participated in a parent protocol.

Detailed Description

This is a 14.5 year LTFU protocol to assess long term safety and clinical response to IP as well as to capture natural disease history of participants not dosed with IP in a parent protocol. No IP is provided as part of this protocol. Participants will remain on standard of care medication as indicated and prescribed by their physicians.

Study Timeline

• Study First Submitted: 2024-12-20
• Study Start: 2024-12-23
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-28
• Last Update Submitted: 2025-01-28
• Study First Posted: 2025-02-03
• Last Update Posted: 2025-02-03
• Primary Completion: 2041-07
• Study Completion: 2041-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Enrolled in an iECURE parent protocol and have either completed or discontinued that protocol
2. Participant parent(s)/LAR is willing and able to adhere to the protocol requirements.
3. Consent was obtained by the participants parent(s)/LAR (and participant assent, where applicable), prior to any study-related data being collected.

Exclusion Criteria

1. Participants who enroll into an interventional drug or gene therapy clinical trial utilizing an IP other than the IP provided in the parent protocol will be excluded from this protocol.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
AE and SAE (incidence, severity, seriousness, and relatedness)	Over 14.5 years post dosing with ECUR-506	Safety
Change from baseline over 14.5 years post infusion in length	Over 14.5 years post dosing with ECUR-506	Length measured in cenitmeters
Change from baseline over 14.5 years post infusion in weight	Over 14.5 years post dosing with ECUR-506	Weight measured in kilograms
Urinalysis (Dip Stick) Evaluations	Over 14.5 years post dosing with ECUR-506	Urinalysis (Dip Stick) will be evaluated to monitor pathological changes to the participants urine and to monitor levels of Specific Gravity, pH, Glucose, Protein, Blood, Ketones, Bilirubin, Urobilinogen, Nitrite, Leukocyte esterase, red blood cell count, and white blood cell count as they relate to established local lab normal ranges.

Secondary Outcome Measures

Name	Time	Method
qPCR measurement to evaluate the clearance of both vectors in blood over time.	Over 14.5 years post dosing with ECUR-506	Pharmacokinetics
qPCR measurement to evaluate the clearance of both vectors in saliva over time.	Over 14.5 years post dosing with ECUR-506	Pharmacokinetics
qPCR measurement to evaluate the clearance of both vectors in urine over time.	Over 14.5 years post dosing with ECUR-506	Pharmacokinetics
qPCR measurement to evaluate the clearance of both vectors in feces over time.	Over 14.5 years post dosing with ECUR-506	Pharmacokinetics
Percent Liver Transduction	Over 14.5 years post dosing with ECUR-506	Pharmacokinetics
Number of hyperammonemic crises (HAC)	Over 14.5 years post dosing with ECUR-506	Pharmacodynamics and Efficacy
Among participants who experience HAC with associated neurological status change and are hospitalized: Asses daily ammonia levels for duration of hospitalization for each event	Over 14.5 years post dosing with ECUR-506	Pharmacodynamics and Safety
Among participants who experience HAC with associated neurological status change and are hospitalized: Assess duration of hospitalization for each event.	Over 14.5 years post dosing with ECUR-506	Pharmacodynamics and Safety
Among participants who experience HAC with associated neurological status change and are hospitalized: Assess requirement for ICU care.	Over 14.5 years post dosing with ECUR-506	Pharmacodynamics and Safety
Number of HAC with the following severities: a. Mild: adjustment of dietary protein intake and oral scavenger medication b. Moderate: cessation of dietary protein intake and initiation of IV scavenger therapy c. Severe: requirement for hemodialysis	Over 14.5 years post dosing with ECUR-506	Pharmacodynamics and Safety
Scavenger drug dose per body surface area (BSA)	Over 14.5 years post dosing with ECUR-506	Efficacy
Protein allowance g/kg	Over 14.5 years post dosing with ECUR-506	Efficacy
Concentration of blood urea nitrogen measurements	Over 14.5 years post dosing with ECUR-506	Pharmacodynamics
Time to liver transplant from Day 1 (Parent Protocol) for participants who are dosed and Day -1 (Parent Protocol) for participants who are not dosed to end of study EOS (LTFU Protocol)	Over 14.5 years post dosing with ECUR-506	Efficacy
Transplant free survival	Over 14.5 years post dosing with ECUR-506	Efficacy
Time to liver transplant or any cause of death from dosing to EOS.	Over 14.5 years post dosing with ECUR-506	Efficacy
Overall Survival: Survival measured from Day 1 (Parent Protocol) for participants who are dosed and Day -1 (Parent Protocol) for participants who are not dosed to end of study EOS (LTFU Protocol).	Over 14.5 years post dosing with ECUR-506	Efficacy
Time to any-cause death from dosing to EOS. Survival measured from Day 1 (Parent Protocol) for participants who are dosed and Day -1 (Parent Protocol) for participants who are not dosed to end of study EOS (LTFU Protocol).	Over 14.5 years post dosing with ECUR-506	Efficacy

Trial Locations

Locations (1)

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom