Gene therapy for Tay-Sachs and related diseases
| ISRCTN | ISRCTN57061190 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN57061190 |
| Protocol serial number | HGM201 |
| Sponsor | Cambridge University Hospitals NHS Foundation Trust (UK) |
| Funders | Medical Research Council, Grant Ref: MR/K025570/1DPFS/DCS, 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, Q4 2010: Application to MRC & NIHR Efficacy and Mechanism Evaluation (EME) Programme jointly with the National Institute of Health Research to support Clinical Trial, Q4 2010 Application to Regional Clinical Research network for infrastructure support for clinical trial coordinator and nursing and ancillary healthcare staff |
- 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 of protocol
Not provided at time of registration
Contact information
Prof Timothy Cox
Scientific
Scientific
Department of Medicine
University of Cambridge
Box 157, Level 5
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
| Phone | +44 (0)1223 336864 |
|---|---|
| tmc12@medschl.cam.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-centre open-label interventional trial |
| Secondary study design | Non randomised study |
| Study type | Participant 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 objectives | 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 |
| Health condition(s) or problem(s) studied | 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(s) |
No acute or sub-acute events causing deterioration in neurological function or impaired structural integrity of central nervous system. |
| Key secondary outcome measure(s) |
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. |
| Completion date | 28/02/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 3 Months |
| Upper age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 12 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/03/2012 |
| Date of final enrolment | 28/02/2015 |
Locations
Countries of recruitment
- United Kingdom
- England
- Cyprus
- Czech Republic
- France
- Germany
- Greece
- Israel
- Italy
- Netherlands
- Poland
- Portugal
- Türkiye
Study participating centre
University of Cambridge
Cambridge
CB2 0QQ
United Kingdom
CB2 0QQ
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
25/06/2020: No publications found.
