Halting Ornithine Transcarbamylase Deficiency With Recombinant AAV in ChildrEn
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age0-16
SponsorUniversity College, London
About this trial
Ornithine transcarbamylase deficiency (OTCD) is an inherited metabolic liver disease which means that the body cannot maintain normal levels of ammonia. Ammonia levels can rise (called hyperammonaemic decompensations) which can be life-threatening and may result in impaired neurological development in children. OTCD is a rare genetic disorder characterised by complete or partial lack of the enzyme ornithine transcarbamylase (OTC).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient (male or female) aged ≤16 years at time of written informed consent. For the dose escalation phase patients must be aged 6-16, for the dose expansion phase patients must be aged 0-16 (at the time of written informed consent).
OTC deficiency confirmed via enzymatic or molecular analysis. This may include identification of pathogenic mutations or liver OTC activity that is <20% of normal activity.
Patient has severe disease defined by reduced protein allowance and prescribed at least one ammonia scavenger drug.
Patient (if capable of signing) and parents or legal representative have signed a written informed consent form.
Disqualifiers
Titres of the neutralising antibodies against AAV-LK03 >1:5 serum dilution.
Significant hepatic inflammation as evidenced by the following laboratory abnormalities: alanine aminotransferase or aspartate aminotransferase or bilirubin >2 x upper limit of normal (ULN), alkaline phosphatase >3 x ULN.
Evidence of severe unexplained liver disease including but not limited to liver malignancy, liver cirrhosis, or acute liver failure.
Evidence of active hepatitis B or C virus (HBV and HCV respectively) documented by hepatitis B surface antigen (HBsAg) or HCV RNA positivity.
Trial design
Design model
Single group
Treatments tested in this trial
AAVLK03hOTC
GeneticPeripheral intravenous infusion of AAVLK03hOTC.
Treatment groups
12 Participants
are divided into 1 treatment groupGroup A: AAVLK03hOTC (also known as ssAAV-LK03.hAAT.hcoOTC)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety - adverse events
Incidence of adverse events (AEs), treatment-related adverse events and serious adverse events (SAEs) for each dosing group assessed by severity and relationship to study product.
Time frame
12 months post-infusionSecondary outcomes
1
Safety outcomes
• Change from baseline level of transaminases (AST and ALT).
Time frame
Over 12 months post-infusion2
Safety outcomes
Change from baseline level of humoral and cellular immune responses the AAV-LK03 capsid.
Time frame
Over 12 months post-infusion3
Safety outcomes
• Change from baseline level of cellular immune against hOTC.
Time frame
Over 12 months post-infusion4
Safety outcomes
• Viral shedding: plasma/saliva/urine/stool samples.
Time frame
Over 12 months post-infusionOther outcomes
1
Exploratory outcomes
• Change from baseline neurocognitive assessment, as measured by the Bayley - III for participants aged 6months to 3 years
Time frame
Over 12 months post-infusion2
Exploratory outcomes
• Change from baseline neurocognitive assessment as measured WPPSI-IV for participants aged 2 years 6 months to 7 years 7 months
Time frame
Over 12 months post-infusion3
Exploratory outcomes
• Change from baseline neurocognitive assessment as measured by the WISC-V for participants aged 6 years to 16 years and 11months
Time frame
Over 12 months post-infusion4
Exploratory outcomes
• Change from baseline behavioural assessment as measured by the Child Behaviour Checklist
Time frame
Over 12 months post-infusionSponsors and contacts
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Source ClinicalTrials.gov