A safety and dose finding study of DTX301 in late onset OTC deficiency
Research type
Research Study
Full title
A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Adults with Late-Onset OTC Deficiency
IRAS ID
211800
Contact name
Robin Lachmann
Contact email
Sponsor organisation
Dimension Therapeutics, Inc.
Eudract number
2016-001057-40
Duration of Study in the UK
1 years, 6 months, 16 days
Research summary
Summary of Research
Ornithine transcarbamylase (OTC) deficiency is a rare genetic metabolic disorder associated with the liver. OTC is a liver enzyme which helps rid the body of ammonia, a toxic breakdown product of dietary protein. These patients have a defective OTC gene. This results in ammonia accumulation in the blood which can lead to difficulty concentrating, seizures and coma.\n\nStudy 301OTC01 is sponsored by Dimension Therapeutics, Inc. The primary reason of this study is to determine the safety of a single intravenous dose of DTX301 in adults with late-onset OTC deficiency. Up to 12 participants will take part from research sites worldwide. Three participants will receive dose level1(the lowest dose) and a minimum of 2 to 3 participants will receive each subsequent dose. The decision to start the next dose level will be made by an independent Data Monitoring Committee which will oversee the safety of the trial. \n\nPart of DTX301 contains a non-disease causing virus, which has been modified in a laboratory and paired with working copies of the human OTC gene to liver cells. DTX301 is experimental and has not yet been shown to be safe or effective. This will be the first time DTX301 will be given to humans.\n\nUnlike current medical treatment options (dietary restriction and ammonia scavengers), DTX301 may offer the potential to correct the underlying deficiency for a prolonged period of time.\n\nParticipants will be in the study for approximately 56 weeks (including a 4 week screening). During the study, patients are scheduled for approximately 12 hospital visits, of which 5 will involve overnight stays. An additional 16 study visits will be scheduled as outpatient clinic or home visits.\n\nStudy procedures include: medical history, ECG, physical examinations, bloods tests, urine, saliva and stool tests, quality of life questionnaires, as well as tests of memory and concentration.
Summary of Results
A PDF of the lay summary can be found on https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.ultragenyx.com%2Fclinical-trials%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cce7c1d2a4c834948897308dae1a639f6%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638070401296295066%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=GlVgfE8bJjaGBmBTq90EW%2FHdAGXjshEkaM7wMi6fpOg%3D&reserved=0
REC name
London - West London & GTAC Research Ethics Committee
REC reference
17/LO/0001
Date of REC Opinion
4 May 2017
REC opinion
Further Information Favourable Opinion