Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease, Urea Cycle Disorders, Inborn
Conditions
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
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.
Interventions
OTHERNo Intervention
No Intervention
Sponsors
iECURE, Inc.
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
7 Months to 15 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United Kingdom, United States
Contacts
CONTACTGeorge Diaz, M.D., Ph.D.
STUDY_DIRECTORGeorge Diaz, M.D., Ph.D
iECURE, Inc.
Outcome results
None listed