Actively Recruiting
Phase I/II Open Label Multicentre Trial to Assess Safety and Efficacy of AAVLK03hOTC Gene Therapy for Children With Ornithine Transcarbamylase Deficiency
Led by University College, London · Updated on 2023-11-07
12
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Ornithine transcarbamylase deficiency (OTCD) is a rare inherited liver disorder that prevents the body from maintaining normal ammonia levels, leading to dangerous ammonia buildup in the blood. This condition can cause life-threatening episodes called hyperammonaemic decompensations, which may result in vomiting, movement problems, lethargy, coma, and impaired neurological development in children. Current treatments include drugs to reduce ammonia and low-protein diets, but these do not always prevent these dangerous episodes. Liver transplantation can be life-saving but may be delayed, risking further neurological harm. The trial is testing a gene therapy called AAVLK03hOTC, designed to target the liver and enable production of the missing OTC enzyme. The study involves escalating doses given by intravenous infusion in children from birth to 16 years old, with groups receiving low to high doses and an additional group receiving the dose with the best safety and efficacy balance. This gene therapy aims to help the liver function normally, reduce dangerous ammonia buildups, and act as a bridge to liver transplant. Participants will be closely monitored for safety and effectiveness for at least 12 months after infusion, including tracking any adverse events. Long-term follow-up of up to four years will assess ongoing safety. Researchers will regularly assess ammonia levels, liver function, and overall health to understand the gene therapy's impact on managing OTCD. The study is open-label and involves multiple centers, aiming to provide important information on this new treatment option for children with OTCD.
CONDITIONS
Brief Title
Halting Ornithine Transcarbamylase Deficiency With Recombinant AAV in ChildrEn
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patient aged 6 to 16 years for dose escalation phase, or 0 to 16 years for dose expansion phase at time of consent
- Confirmed ornithine transcarbamylase deficiency by enzymatic or molecular analysis
- Severe disease requiring reduced protein allowance and at least one prescribed ammonia scavenger drug
- Patient and parent or legal representative have signed informed consent
- Females of childbearing potential have negative pregnancy tests and use effective contraception during study
- Sexually active boys use contraception from at least 14 days before infusion until 4 weeks after last negative test or week 52
- Baseline ammonia level below 100 µmol/L and within historical stable range
- Stable dose of ammonia scavenger and protein allowance for 4 weeks before baseline
- Willing to commit to 4 years of long-term safety follow-up
You will not qualify if you...
- Neutralising antibody titres against AAV-LK03 greater than 1:5 serum dilution
- Significant liver inflammation with certain elevated liver enzymes or bilirubin
- Severe unexplained liver disease such as malignancy, cirrhosis, or acute liver failure
- Active hepatitis B or C infection
- Positive test for HIV
- Prior liver transplant or hepatocyte/cell infusion
- Participation in another clinical trial within previous 12 months
- Contraindication to immunosuppression
- Active bacterial or viral infection
- Pregnant or breastfeeding females
- Other serious medical conditions including malignancy or severe organ impairment
- Any other condition or disability that may affect optimal participation according to investigator opinion
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 months post-infusion
Participants receive a single intravenous infusion of gene therapy (AAVLK03hOTC) to help the liver produce the OTC enzyme and reduce ammonia levels.
Regular visits for safety and efficacy assessments over 12 months
Duration - Up to 4 years
Participants are monitored for long-term safety and efficacy outcomes after the gene therapy infusion.
Periodic follow-up visits during the long-term safety follow-up period
Trial Site Locations
Total: 1 location
1
Great Ormond Street Hospital
London, United Kingdom, WC1N 3JH
Actively Recruiting
Research Team
T
Trial Manager
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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