Condition category
Nutritional, Metabolic, Endocrine
Date applied
12/09/2010
Date assigned
06/10/2010
Last edited
12/06/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Timothy Cox

ORCID ID

Contact details

Department of Medicine
University of Cambridge
Box 157
Level 5
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 336864
tmc12@medschl.cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HGM201

Study information

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

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

Not provided at time of registration

Study design

Single-centre open-label interventional trial

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Not Applicable

Drug names

Primary outcome measures

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 trial start date

01/03/2012

Overall trial end date

28/02/2015

Reason abandoned

Eligibility

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 type

Patient

Age group

Child

Gender

Both

Target number of participants

12

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, France, Germany, Greece, Israel, Italy, Netherlands, Poland, Portugal, Turkey, United Kingdom

Trial participating centre

Department of Medicine
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

Box 277
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 348179
sabine.klager@addenbrookes.nhs.uk

Sponsor type

Government

Website

http://www.cambridge-biomedical.co.uk/science

Funders

Funder type

Government

Funder name

Current sources of funding as of 12/06/2014:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medical Research Council (UK), Grant Ref: MR/K025570/1DPFS/DCS

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Applications for funding in progress at time of registration:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes