Intra-cerebral gene therapy for Sanfilippo type B syndrome

• Register: ISRCTN
• Last refreshed on: 11 October 2021
• Main ID: ISRCTN19853672
• Date of registration: 03/08/2011
• Prospective Registration: Yes
• Primary sponsor: Institut Pasteur (France)
• Public title: Intra-cerebral gene therapy for Sanfilippo type B syndrome
• Scientific title: A phase I/II, open-label, study of intracerebral administration of adeno-associated viral vectors carrying human NaGlu cDNA for the treatment of Sanfilippo type B syndrome
• Date of first enrolment: 01/09/2013
• Target sample size: 4
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN19853672
• Study type: Interventional
• Study design: Phase I/II single-arm open-label study (Treatment)
• Phase: Phase I/II

Countries of recruitment

France

Contacts

• Name: Marc Tardieu

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age: 18 months to the end of the 5th year
2. Onset of clinical manifestations related to MPSIIIB during the first 5 years of life
3. NaGlu activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls
4. Patient affiliated to a social security regimen
5. Family understanding the procedure and the informed consent
6. Vital laboratory parameters within normal range

Sanfilippo disease is a rare disease and so the countries of recruitment will depend on the availabilities of the patient at the time of recruitment. There will be one study centre in France.

Exclusion criteria:
1. Presence of brain atrophy on pre-inclusion MRI judged on a cortico-dural distance of more than 1 cm
2. Any condition that would contraindicate permanently anaesthesia
3. Any other permanent medical condition not related to MPSIIIB
4. No independent walking (Ability to walk without help)
5. Any vaccination 1 month before vector injection
6. Receipt of aspirin within one month
7. Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Mucopolysaccharidose - neurodegenerative disease
Nutritional, Metabolic, Endocrine
Mucopolysaccharidosis

Intervention(s)

Patients will receive gene therapy combined with immunosuppressant regimen. The vector is a serotype 2 AAV genome encoding the human a-N-acetylglucosaminidase cDNA packaged in a serotype 5 capsid called AAV-NAGLU. Vector suspensions will be simultaneously injected into the brain parenchyma at 6 injections sites in a single neurosurgical session. Combined immunosuppression (Tacrolimus, Cell-Cept) is justified by previous studies in children receiving recombinant enzyme infusions and investigations of AAV-mediated gene therapy in Sanfilippo and Hurler dogs.

Clinical and radiological examination, collection of biological products including blood, peripheral blood mononucleated cells and cerebrospinal fluid (CSF) > 6 weeks prior to treatment, at inclusion, baseline, 14 days prior to treatment, observation and -2 and -1 days, daily follow-up during 1 week post-injection, then 14 and 21 days, 1, 3, 6 and 12 months post-treatment.

The total duration of follow up is 1 year.

Added 02/08/2013:
Vectors will be delivered through 8 small burr holes. Two in the posterior fossa to target the white matter of the cerebellar hemisphers and six supratentorially, to target the white matter adjacent to the putamen. Two deposits will be done on each track, one deep and one superficial, in a single neurosurgical session.

Primary Outcome(s)

Clinical, radiological, biological tolerance associated to the proposed treatment

Secondary Outcome(s)

Collection of data to define exploratory tests that will become evaluation criteria for further clinical phase III efficacy studies (brain MRI; neurological and biological markers)

Secondary ID(s)

MPS3-IP-01

Source(s) of Monetary Support

French Patient Association (France), Private donations (France)

Ethics review

Status:
Approval date:
Contact:

CCP Il-de-France II, 17/04/2013, ref: 2013-03-17

Results

• Results available: Yes
• Date Completed: 01/11/2015