Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

UniQure

Status and phase: Completed; Phase 2; Phase 1

Conditions: Sanfilippo Syndrome B

Treatments: Drug: rAAV2/5-hNAGLU

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03300453

AMT110-CD-001

Details and patient eligibility

About

This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.

Full description

This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.

Four patients, 18 months up to the 5th birthday, have been included.

The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1 year post-surgery. The duration of the first extension phase is 18 months. The duration of the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be 66 months

Enrollment: 4 patients

Sex: All

Ages: 18 to 60 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age: 18 months up to 60 months (5th birthday);
• Onset of clinical manifestations related to mucopolysaccharidosis type IIIB (MPSIIIB);
• NAGLU activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls;
• Patient affiliated to, or covered by a French social security regimen, or European patients with European Health Insurance Card;
• Family understanding the procedure and the informed consent;
• Signed informed consent by both parents or legal representative;
• Vital laboratory parameters within normal range.

Exclusion criteria

• Presence of brain atrophy on baseline MRI judged on a cortico-dural distance of more than 0.6 cm;
• Any condition that would contraindicate general anesthesia;
• Any other permanent medical condition not related to MPSIIIB that could contraindicate the study participation;
• No independent walking (ability to walk without help);
• Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection (sleep and mood regulators are accepted);
• Any condition that would contraindicate treatment with Modigraf®, Cellcept® and prednisolone (Solupred® and Solumedrol®).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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4 participants in 1 patient group

rAAV2/5-hNAGLU

Experimental group

Description:

Each patient will receive 960 µL of vector suspension. The vector suspension will be deposited simultaneously at 16 sites, each deposit containing 2.4x 1011 vg (4x1012 vg in total).

Treatment:

Drug: rAAV2/5-hNAGLU