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

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.

Study Overview

• Status: Recruiting
• Conditions: Urea Cycle Disorders, Inborn; Ornithine Transcarbamylase Deficiency; Ornithine Transcarbamylase Deficiency Disease
• Intervention / Treatment: Other: No Intervention

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 Type: Observational
• Enrollment (Estimated): 13

Contacts and Locations

• Study Contact: Name: George Diaz, M.D., Ph.D.; Phone Number: 1-877-694-3558; Email: medinfo@iecure.com

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital
    • Contact: Christopher Jackson; Email: christopher.jackson@gosh.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All participants from an iECURE parent treatment protocol, whether they received IP or not, will be consented to enter this LTFU study. Enrollment into the LTFU will begin upon either premature discontinuation from, or completion of, the parent treatment protocol.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Enrolled and Dosed; Previously dosed in a previous iECURE study.	Other: No Intervention; No Intervention
Enrolled but Not Dosed; Enrolled in a previous iECURE study, but not dosed.	Other: No Intervention; No Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE and SAE (incidence, severity, seriousness, and relatedness)	Safety	Over 14.5 years post dosing with ECUR-506
Change from baseline over 14.5 years post infusion in length	Length measured in cenitmeters	Over 14.5 years post dosing with ECUR-506
Change from baseline over 14.5 years post infusion in weight	Weight measured in kilograms	Over 14.5 years post dosing with ECUR-506
Urinalysis (Dip Stick) Evaluations	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.	Over 14.5 years post dosing with ECUR-506

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
qPCR measurement to evaluate the clearance of both vectors in blood over time.	Pharmacokinetics	Over 14.5 years post dosing with ECUR-506
qPCR measurement to evaluate the clearance of both vectors in saliva over time.	Pharmacokinetics	Over 14.5 years post dosing with ECUR-506
qPCR measurement to evaluate the clearance of both vectors in urine over time.	Pharmacokinetics	Over 14.5 years post dosing with ECUR-506
qPCR measurement to evaluate the clearance of both vectors in feces over time.	Pharmacokinetics	Over 14.5 years post dosing with ECUR-506
Percent Liver Transduction	Pharmacokinetics	Over 14.5 years post dosing with ECUR-506
Number of hyperammonemic crises (HAC)	Pharmacodynamics and Efficacy	Over 14.5 years post dosing with ECUR-506
Among participants who experience HAC with associated neurological status change and are hospitalized: Asses daily ammonia levels for duration of hospitalization for each event	Pharmacodynamics and Safety	Over 14.5 years post dosing with ECUR-506
Among participants who experience HAC with associated neurological status change and are hospitalized: Assess duration of hospitalization for each event.	Pharmacodynamics and Safety	Over 14.5 years post dosing with ECUR-506
Among participants who experience HAC with associated neurological status change and are hospitalized: Assess requirement for ICU care.	Pharmacodynamics and Safety	Over 14.5 years post dosing with ECUR-506
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	Pharmacodynamics and Safety	Over 14.5 years post dosing with ECUR-506
Scavenger drug dose per body surface area (BSA)	Efficacy	Over 14.5 years post dosing with ECUR-506
Protein allowance g/kg	Efficacy	Over 14.5 years post dosing with ECUR-506
Concentration of blood urea nitrogen measurements	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
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)	Efficacy	Over 14.5 years post dosing with ECUR-506
Transplant free survival	Efficacy	Over 14.5 years post dosing with ECUR-506
Time to liver transplant or any cause of death from dosing to EOS.	Efficacy	Over 14.5 years post dosing with ECUR-506
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).	Efficacy	Over 14.5 years post dosing with ECUR-506
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).	Efficacy	Over 14.5 years post dosing with ECUR-506

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with antibodies to hOTC in blood.	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
Number of participants with antibodies to M2PCSK9 in blood.	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
Number of participants with antibodies to AAVrh79 in blood.	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
Concentration of plasma ammonia	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
Concentration of plasma citrulline	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
Concentration of plasma glutamine	Pharmacodynamics	Over 14.5 years post dosing with ECUR-506
Urinary excretion of phenylacetate metabolites.	Urinary phenylactate (mcg/mL), urinary phenylactylglutamine (mcg/mL), urinary phenylacetate/ phenylglutamine ratio.	Over 14.5 years post dosing with ECUR-506
Urinary excretion of orotic acid metabolites	Urinary orotic acid (mmol/mol creatinine), urinary uracil (mmol/mol creatinine)	Over 14.5 years post dosing with ECUR-506
Future DNA analysis of WBCs collected in a parent trial may be performed only in the event of an observed genomic safety signal	Safety	Over 14.5 years post dosing with ECUR-506
Developmental assessments as measured by age-appropriate Bayley Scale of Infant Development IV (BSID-IV)	Total Raw Scores, Growth Score Values (GSVs), and Age Equivalent Scores will be analyzed; Raw Scores range 0-162; GSVs range 428-599; Age Equivalent Scores range 1-42 months; a higher score reflects a higher level of skill.	Over 14.5 years post dosing with ECUR-506
Kaufman Assessment Battery for Children - Second Edition Normative Update (KABC-II NU)	Total Raw Scores, Growth Score Values (GSVs), and Age Equivalent Scores will be analyzed; Raw Scores range 0-162; GSVs range 428-599; Age Equivalent Scores range 1-42 months; a higher score reflects a higher level of skill.	Over 14.5 years post dosing with ECUR-506
Quality of life as measured by an age-appropriate Pediatric Quality of Life Inventory Infant Scales	Quality of Life Outcomes	Over 14.5 years post dosing with ECUR-506

Collaborators and Investigators

• Sponsor: iECURE, Inc.
• Investigators: Study Director: George Diaz, M.D., Ph.D, iECURE, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2024
• Primary Completion (Estimated): July 1, 2041
• Study Completion (Estimated): July 1, 2041

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Nervous System Diseases; UCD; Central Nervous System Diseases; Liver Disease; Genetic Diseases, Inborn; Ammonia; Neonatal; Brain Diseases; Metabolic Diseases; Metabolism; Metabolism, Inborn Errors; Long Term Follow Up; Urea Cycle Disorders; Liver Transplant; Brain Diseases, Metabolic, Inborn; Genetic Diseases, X-Linked; Inborn; Inborn Errors; OTC; Brain Diseases, Metabolic; OTC Deficiency; OTCD; Ornithine; Transcarbamylase; Ornithine Transcarbamylase Deficiency; Hyperammonemia; LTFU; Amino Acid Metabolism, Inborn Errors; High Ammonia; NH4; Long-Term Follow-Up
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Nutrition Disorders; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Genetic Diseases, X-Linked; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Malnutrition; Deficiency Diseases; Ornithine Carbamoyltransferase Deficiency Disease; Urea Cycle Disorders, Inborn
• Other Study ID Numbers: ECUR-LTFU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No