Gene therapy for Tay-Sachs and related diseases

ISRCTN	ISRCTN57061190
DOI	https://doi.org/10.1186/ISRCTN57061190
Secondary identifying numbers	HGM201

Submission date: 12/09/2010
Registration date: 06/10/2010
Last edited: 25/06/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Not provided at time of registration

Contact information

Prof Timothy Cox
Scientific

Department of Medicine
University of Cambridge
Box 157, Level 5
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom

Phone	+44 (0)1223 336864
Email	tmc12@medschl.cam.ac.uk

Study information

Study design	Single-centre open-label interventional trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Phase I/II open-label trial to determine the safety and tolerability of intracranial gene therapy in GM2 gangliosidosis using recombinant adeno-associated viral vectors
Study acronym	SAVVY CHILD
Study hypothesis	Intracerebral and intraventricular rAAV vectors will safely deliver potentially therapeutic hexosaminidase A and B isozymes in patients with GM2 gangliosidosis.
Ethics approval(s)	Not provided at time of registration
Condition	Tay-Sachs disease, Sandhoff disease
Intervention	Single interventional event: neurosurgical delivery of monocistronic rAAV vectors harbouring α and ß human hexosaminidase transgenes by intracranial injection, depositing at 12 sites with supplementary infusion into cerebrospinal fluid spaces ~1012 genome copies per locus delivered within 36 h. No placebo or interventional control group is possible. At recruitment: intensive rapid neurological, motor development and neuropsychological evaluation with sample collection and banking. Follow-up: safety and tolerance: clinical examination twice daily for 7 days after procedure, weekly for 1 month then every month for 6 months; every 2 months thereafter for 2 years to exclude signs of haemorrhage, systemic infection, immune reactions and encephalitis. CSF testing will be conducted as appropriate but pre-procedure and within 2 weeks of vector administration; thereafter at intervals alongside MRI (including DTwi and MR spectroscopy), to exclude leukoencephalopathy and incidental lesions before procedure and at day 7; further studies at 3, 6 12 and 24 months to evaluate necrosis and cortical conformation and thickness afterwards. Six monthly neuro-developmental (if relevant) and neuropsychological testing. The total duration of the study will be 3 years.
Intervention type	Other
Primary outcome measure	No acute or sub-acute events causing deterioration in neurological function or impaired structural integrity of central nervous system.
Secondary outcome measures	Secondary end-point criteria on which phase III efficacy studies will be predicated, will compare outcomes in siblings with disease in affected pedigrees with Tay-Sachs and related diseases, as well as population data on the natural course of GM2 gangliosidosis. Procedures include banking of biological samples and interval neuropsychological evaluation.
Overall study start date	01/03/2012
Overall study end date	28/02/2015

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	3 Months
Upper age limit	18 Years
Sex	Both
Target number of participants	12
Participant inclusion criteria	1. Male and female infants and young subjects aged 3 months to 18 years 2. GM2 gangliosidosis confirmed by biochemical analysis and molecular analysis of cognate HEXA or HEXB genes in the presymptomatic phase with normal neuromotor development, physical examination and cerebral MR imaging
Participant exclusion criteria	1. GM2 activator deficiency 2. Developmental regression or other features of symptomatic GM2 gangliosidosis 3. Clinical or radiological abnormalities of the central nervous system
Recruitment start date	01/03/2012
Recruitment end date	28/02/2015

Locations

Countries of recruitment

Cyprus
Czech Republic
England
France
Germany
Greece
Israel
Italy
Netherlands
Poland
Portugal
Türkiye
United Kingdom

Study participating centre

University of Cambridge

Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Box 277
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Phone	+44 (0)1223 348179
Email	sabine.klager@addenbrookes.nhs.uk
Website	http://www.cambridge-biomedical.co.uk/science
"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Government

Medical Research Council, Grant Ref: MR/K025570/1DPFS/DCS
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Proposal in preparation collaboration with Institute Pasteur (coordinator: Prof. J.-M. Heard) in submission to European Union, Framework Package 7. Gene therapy of the brain in lysosomal storage diseases, Acronym: LSDGT. This will seek support for the industrial collaborator and preparation of the Investigational Medicinal Product - call

No information available

Q4 2010: Application to MRC & NIHR Efficacy and Mechanism Evaluation (EME) Programme jointly with the National Institute of Health Research to support Clinical Trial

No information available

Q4 2010 Application to Regional Clinical Research network for infrastructure support for clinical trial coordinator and nursing and ancillary healthcare staff

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

25/06/2020: No publications found.