A Phase I/II Gene Transfer Study in Mucopolysaccharidosis IIIB
Research type
Research Study
Full title
Phase I/II gene transfer clinical trial of rAAV9.CMV.hNAGLU for Mucopolysaccharidosis (MPS) IIIB
IRAS ID
253258
Contact name
Suresh Vijay
Contact email
Sponsor organisation
Abeona Therapeutics Inc.
Eudract number
2014-001411-39
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 6 months, 1 days
Research summary
Mucopolysaccharidosis III (MPS III) is a rare disease with an estimated incidence of 1 in 70,000 births. People with MPS IIIB show errors with the gene carrying instructions for the production of the enzyme known as alpha-N-acetylglucosaminidase (NAGLU) that naturally metabolises substances in the body known as glycosaminoglycans (GAGs). MPS IIIB is caused by the build-up of these GAGs in many parts of the body. This is a severe progressive disease mainly affecting the brain. There is currently no treatment available for the disease.
This Phase I/II clinical trial (Sponsored by Abeona) is a first in human, open-label, dose-escalation study of intravenous ABO-101 in MPS IIIB subjects aged ≥ 6 months. AB0-101 is a viral vector (a tool that can deliver genetic material into cells) that will be used to introduce the missing NAGLU gene into the body cells. The study will assess the safety and efficacy of ABO-101 according to the relevant endpoints identified during a recently-completed natural history study. This clinical trial ABT-002 initiated as a single site dose escalation clinical trial study at Nationwide Children Hospital (Ohio, USA) but has now advanced to a multi-centre study with the addition of up to 10 trial sites in USA and Europe. Enrolment in the first cohort 1 (Cohort 1, low dose, N=3) has started. For Cohort 2, patients will receive a single high dose (N=3-6). Safety is the primary outcome for this study with several secondary outcome measures (some of which are exploratory). Safety follow-up will continue for 2 years.
In pre-clinical studies, a single intravenous injection of a vector carrying the human NAGLU gene restored the NAGLU activity and corrected the GAG content throughout the central nervous system. In addition, no significant side effects have been seen in preclinical studies. The investigator brochure describes some cardiomyopathy and acute liver toxicity at the higher dose in mice and primates, but this dose is four times higher than the high dose in humans. Therefore this gene therapy shows potential to improve the quality of life in MPS IIIB patients using this clinical application.
REC name
North East - York Research Ethics Committee
REC reference
18/NE/0337
Date of REC Opinion
5 Dec 2018
REC opinion
Further Information Favourable Opinion