Clinical trial NCT03300453: Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome
Official title: Protocol AMT110-CD-001: A Phase I/II, Open-label, Study of Intracerebral Administration of Adeno-associated Viral Vector Containing the Human Alpha-N-acetylglucosaminidase cDNA in Children With Sanfilippo Type B Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sanfilippo Syndrome B
Lead sponsor: UniQure Biopharma B.V.
Sponsor class: INDUSTRY
Collaborators: name: Venn Life Sciences
name: Institut Pasteur
First posted: 2017-10-03
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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

Eligibility criteria: 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®).

Primary outcomes:
measure: Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline
timeFrame: Baseline until end of study (Month 66)
Secondary outcomes:
measure: Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI
timeFrame: Baseline until end of study (Month 66)
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopitaux Universitaires Paris-Sud
state: Le Kremlin-Bicetre Cedex
Study officials:
affiliation: Hopitaux Universitaires Paris-Sud
name: Kumaran Deiva, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gougeon ML, Poirier-Beaudouin B, Ausseil J, Zerah M, Artaud C, Heard JM, Deiva K, Tardieu M. Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome. Front Immunol. 2021 May 10;12:655478. doi: 10.3389/fimmu.2021.655478. eCollection 2021.