Clinical trial NCT06805695: Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Official title: Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ornithine Transcarbamylase Deficiency
Ornithine Transcarbamylase Deficiency Disease
Urea Cycle Disorders, Inborn
Keywords: Amino Acid Metabolism, Inborn Errors
Ammonia
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
High Ammonia
Hyperammonemia
Inborn
Inborn Errors
Liver Disease
Liver Transplant
Metabolism
Metabolic Diseases
Metabolism, Inborn Errors
Neonatal
Nervous System Diseases
NH4
Ornithine
Ornithine Transcarbamylase Deficiency
OTC
OTC Deficiency
OTCD
Transcarbamylase
UCD
Urea Cycle Disorders
Long Term Follow Up
Long-Term Follow-Up
LTFU
Lead sponsor: iECURE, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-03
Enrollment: 13
Sex: ALL
Minimum age (years): 7
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AE and SAE (incidence, severity, seriousness, and relatedness)
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Change from baseline over 14.5 years post infusion in length
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Change from baseline over 14.5 years post infusion in weight
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Urinalysis (Dip Stick) Evaluations
timeFrame: Over 14.5 years post dosing with ECUR-506
Secondary outcomes:
measure: qPCR measurement to evaluate the clearance of both vectors in blood over time.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: qPCR measurement to evaluate the clearance of both vectors in saliva over time.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: qPCR measurement to evaluate the clearance of both vectors in urine over time.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: qPCR measurement to evaluate the clearance of both vectors in feces over time.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Percent Liver Transduction
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Number of hyperammonemic crises (HAC)
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Among participants who experience HAC with associated neurological status change and are hospitalized: Asses daily ammonia levels for duration of hospitalization for each event
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Among participants who experience HAC with associated neurological status change and are hospitalized: Assess duration of hospitalization for each event.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Among participants who experience HAC with associated neurological status change and are hospitalized: Assess requirement for ICU care.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: 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
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Scavenger drug dose per body surface area (BSA)
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Protein allowance g/kg
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Concentration of blood urea nitrogen measurements
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: 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)
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Transplant free survival
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Time to liver transplant or any cause of death from dosing to EOS.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: 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).
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: 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).
timeFrame: Over 14.5 years post dosing with ECUR-506
Other outcomes:
measure: Number of participants with antibodies to hOTC in blood.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Number of participants with antibodies to M2PCSK9 in blood.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Number of participants with antibodies to AAVrh79 in blood.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Concentration of plasma ammonia
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Concentration of plasma citrulline
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Concentration of plasma glutamine
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Urinary excretion of phenylacetate metabolites.
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Urinary excretion of orotic acid metabolites
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Future DNA analysis of WBCs collected in a parent trial may be performed only in the event of an observed genomic safety signal
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Developmental assessments as measured by age-appropriate Bayley Scale of Infant Development IV (BSID-IV)
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Kaufman Assessment Battery for Children - Second Edition Normative Update (KABC-II NU)
timeFrame: Over 14.5 years post dosing with ECUR-506
measure: Quality of life as measured by an age-appropriate Pediatric Quality of Life Inventory Infant Scales
timeFrame: Over 14.5 years post dosing with ECUR-506
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: iECURE, Inc.
name: George Diaz, M.D., Ph.D
role: STUDY_DIRECTOR
References: