RecruitingPHASE1, PHASE2INTERVENTIONAL

Halting Ornithine Transcarbamylase Deficiency With Recombinant AAV in ChildrEn

This study, called HORACE, is investigating a new gene therapy for children up to 16 years old who have Ornithine Transcarbamylase Deficiency (OTCD). OTCD is a rare inherited liver condition where the body struggles to break down harmful ammonia, leading to dangerous levels that can affect brain development. The gene therapy, given as a single injection, targets the liver to help it make a missing enzyme called OTC. Researchers hope this treatment will enable the liver to work properly, reduce life-threatening ammonia spikes, and minimise brain damage. It could also provide a temporary solution, a 'bridge-to-transplant,' allowing children to grow healthier while waiting for a liver transplant.

At a glance

Status

Recruiting

Phase

PHASE1, PHASE2

Sponsor

University College, London

Enrolment target

Start

01 Nov 2023

Estimated completion

30 Jun 2027

Ornithine Transcarbamylase Deficiency

What is this study about?

If your child has Ornithine Transcarbamylase Deficiency (OTCD), their liver has trouble getting rid of extra nitrogen from the body. This nitrogen then builds up as a harmful substance called ammonia. Too much ammonia can make children very unwell, with symptoms like being sick, having trouble moving, and becoming very sleepy. If not treated quickly, these high ammonia levels can become life-threatening or even lead to a coma, and can also harm brain development.

Currently, children with OTCD manage their condition with special medicines that help remove ammonia and by following a strict low-protein diet. However, even with these treatments, dangerous ammonia spikes can still happen. A liver transplant can cure OTCD, but waiting for a suitable liver can take a long time, and brain damage might occur during this wait.

This study, called HORACE, is exploring a new approach using 'gene therapy.' This treatment aims to deliver a working copy of the gene directly to the liver so it can start producing the missing enzyme (OTC). The researchers hope that just one injection of this gene therapy could help your child's liver work better, reduce the dangerous ammonia spikes, and lower the associated risks. It might even help them stay healthier while waiting for a liver transplant, potentially reducing long-term problems with their brain.

Key takeaways

New gene therapy for children with a rare liver condition (OTCD).
Aims to help the liver process harmful ammonia.
Could reduce dangerous ammonia spikes and protect brain development.
Potential 'bridge' to a liver transplant.
Single injection, followed by long-term health monitoring.
Participation requires a commitment to follow-up for several years.

Who may be eligible?

This study is for boys and girls up to 16 years old who have been diagnosed with Ornithine Transcarbamylase Deficiency (OTCD). For the very first part of the study (called the 'dose escalation phase'), children must be between 6 and 16 years old. Afterwards, for the main part of the study (the 'dose expansion phase'), children from birth to 16 years old can take part.

To be eligible, your child's OTCD must be severe enough that they need a special diet with reduced protein and are taking at least one medicine to lower ammonia. Their ammonia levels must also be stable and not too high when they start the study. There are also specific medical tests, like antibody checks, that will determine if the treatment is suitable for your child.

Parents or legal guardians must give written permission for their child to join the study. If your child is old enough to understand, they will also be asked to sign. Girls who could become pregnant and sexually active boys will need to use effective contraception during the study and for a period afterwards.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Is your child 16 years old or younger?
Has a doctor confirmed your child has OTCD?
Does your child manage OTCD with a special diet and ammonia-lowering medicines?
Are you able to commit to several years of follow-up appointments?
Is your child's ammonia level stable at the moment?

Answer every question to see your result.

What does participation involve?

If your child joins the study, they will receive a single injection of the study gene therapy. This will involve regular visits to the hospital for check-ups, blood tests, and other assessments to monitor their health and the effects of the treatment. There will be initial frequent follow-up appointments, which will become less frequent over time.

Your child will continue to follow their usual treatment plan, including their special diet and ammonia-lowering medicines, unless the study doctor advises otherwise. You will also need to commit to a long-term safety follow-up for an additional four years after the initial treatment period. The total duration of participation, including this long-term follow-up, will be several years.

Potential risks and benefits

This study is investigating a new treatment, so while there's a hope it could greatly benefit children with OTCD by improving liver function and reducing dangerous ammonia spikes, we don't yet know if it will be effective or what all the potential side effects might be. Potential benefits include a healthier liver, fewer ammonia crises, and a better quality of life, possibly reducing the risk of brain damage. However, like all new medicines, there could be risks, including allergic reactions, side effects from the gene therapy itself, or issues related to the treatment delivery. Your child's medical team will carefully monitor them for any problems. Remember, taking part in any clinical trial is voluntary, and you are free to withdraw your child from the study at any time, for any reason, without it affecting their future medical care.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Great Ormond Street Hospital
Verified postcode
London, United Kingdom· Recruiting

Common questions

What is OTCD?

Ornithine Transcarbamylase Deficiency (OTCD) is a rare inherited liver problem where the body can't properly get rid of a harmful substance called ammonia.

What is gene therapy?

Gene therapy is a new type of treatment that aims to correct problems caused by faulty genes. In this study, it tries to help the liver make a missing enzyme.

Will my child still need their current medicines and diet?

Yes, your child will likely continue their current medicines and special diet while in the study, unless the study doctor tells you otherwise.

How long does the study last?

After treatment, there's a commitment to an additional 4 years of follow-up to monitor your child's long-term health and safety.

Is a liver transplant still an option?

Yes, the gene therapy might even act as a 'bridge,' helping your child stay healthier until a liver transplant, which can be life-saving, becomes available.

How to find out more

Trial Manager

cctu.horace@ucl.ac.uk +44 (0) 20 7907 4669 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.