HORACE
Research type
Research Study
Full title
HORACE Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn Phase I/II open label, multicentre clinical trial to assess safety and efficacy of AAVLK03hOTC for paediatric patients with ornithine transcarbamylase deficiency.
IRAS ID
1003541
Contact name
Anupam Chakrapani
Contact email
Sponsor organisation
University College London
Eudract number
2020-005342-41
ISRCTN Number
TBC
Clinicaltrials.gov Identifier
Research summary
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). OTC is a key element of the urea cycle, which is how the liver breaks down and removes extra nitrogen from the body. For people with OTCD the extra nitrogen builds up in the form of excess ammonia (hyperammonemia) in the blood.
Ammonia is toxic and people with OTCD suffer 'hyperammonaemic decompensations' when ammonia levels in the blood rise too high. The symptoms of these hyperammonaemic decompensations include vomiting, impaired movement, and progressive lethargy. If left untreated these hyperammonaemic decompensations may result in life threatening complications or coma. OTCD is managed with drugs that reduce the amount of ammonia in the blood (ammonia-scavenging drugs) and a low protein diet. However, sometimes hyperammonaemic decompensations still occur.
Liver transplants for people with OTCD can be life-saving but there may be a long wait for a suitable liver and neurological damage may occur before a liver transplant is possible.
The HORACE study is testing a new gene therapy (AAVLK03hOTC) which specifically targets the liver so that it can start making OTC. We hope that a single injection of gene therapy for children with OTCD could help the liver work normally and reduce hyperammonaemic decompensations and their associated risks.
This gene-therapy treatment could serve as a 'bridge-to-transplant' where children could grow up in a metabolically stable condition until a liver transplant is possible. This could minimise longer-term neurological damage caused by hyperammonaemic decompensations.REC name
South Central - Oxford A Research Ethics Committee
REC reference
23/SC/0018
Date of REC Opinion
3 May 2023
REC opinion
Further Information Favourable Opinion