Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enrolled and Dosed | Previously dosed in a previous iECURE study. |
| |
| Enrolled but Not Dosed | Enrolled in a previous iECURE study, but not dosed. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No Intervention | Other | No Intervention |
|
| 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 |
| 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. |
| 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 |
Inclusion Criteria:
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.
Not provided
Not provided
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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| George Diaz, M.D., Ph.D. | Contact | 1-877-694-3558 | medinfo@iecure.com |
| Name | Affiliation | Role |
|---|---|---|
| George Diaz, M.D., Ph.D | iECURE, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Great Ormond Street Hospital | Recruiting | London | United Kingdom |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 |
| 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 |
| ID | Term |
|---|---|
| D020163 | Ornithine Carbamoyltransferase Deficiency Disease |
| D056806 | Urea Cycle Disorders, Inborn |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D001927 | Brain Diseases |
| D001928 | Brain Diseases, Metabolic |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D002493 | Central Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D040181 | Genetic Diseases, X-Linked |
| D022124 | Hyperammonemia |
| D008107 | Liver Diseases |
| D008659 | Metabolic Diseases |
| D008661 | Metabolism, Inborn Errors |
| D009422 | Nervous System Diseases |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004066 | Digestive System Diseases |
Not provided
Not provided