Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

LYSOGENE4 enrolled

Overview

The clinical trial P1-SAF-301 is an open-label, single arm, monocentric, phase I/II clinical study evaluating the tolerance and the safety of intracerebral administration of adeno-associated viral vector serotype 10 carrying the human SGSH and SUMF1 cDNAs for the treatment of Sanfilippo type A syndrome The treatment plan consists on a direct injection of the investigational medicinal product SAF-301 to both sides of the brain through 6 image-guided tracks, with 2 deposits per track, in a single neurosurgical session. The primary objective is to assess the tolerance and the safety associated to the proposed treatment through a one-year follow up. The secondary objective is to collect data to define exploratory tests that could become evaluation criteria for further clinical phase III efficacy studies. Four patients will be included in the clinical trial and will be followed during one year. The enrollment and the follow-up of the patients will take place at Bicêtre Hospital. The Neurosurgery will be performed at Necker-Enfants Malades Hospital. Safety will be evaluating on clinical, radiological and biological parameters.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mucopolysaccharidosis Type III A Sanfilippo Disease Type A

Eligibility

Sex: ALLMin age: 18 MonthsMax age: 6 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age: 18 (eighteen) months to end of 6 (six) years * Onset of clinical manifestations related to MPSIIIA during the first 5 years of life * SGSH activity in peripheral blood cell and / or cultured fibroblast extracts of less than 10% of controls. * Patient affiliated to the French social security or assimilated regimens * Family understanding the procedure and the informed consent * Signed informed consent * Vital laboratory parameters within normal range Exclusion Criteria: * Presence of brain atrophy on inclusion MRI judged on a cortico-dural distance of more than 1cm * No independent walking (Ability to walk without help) * Any condition that would contraindicate permanently anaesthesia * Any other permanent medical condition not related to MPSIIIA * Any vaccination 1 month before investigational drug administration * Intake of aspirin within one month * Any medication aiming at modifying the natural course of MPSIIIA given during the 6 months before vector injection * Any condition that would contraindicate treatment with Prograf®, Modigraf®, Cellcept® and Solupred®

Outcomes

Primary Outcomes

Tolerance and safety

Measured by * adverse events (by type and severity) * clinical parameters (fever, seizure, headache, abnormal somnolence or lethargy, any new neurological symptoms), * radiological parameters (on MRI, any sign of bleeding after surgery, any hypersignal on T2 weighted images or diffusion images that are not at the points of injection, and any necrotic area evaluated through T1-weighted and diffusion imaging as well as modification of lipids in spectroscopy) * biological parameters (in particular anemia, leucopenia, thrombopenia, liver dysfunction)

Time frame: during the one year follow-up

Secondary Outcomes

To collect data to define exploratory tests that could become evaluation criteria for further clinical phase III efficacy studies

* Brain MRI * Neurocognitive/behavioral tests * Biological markers on blood, urine and CSF