Clinical trial NCT01474343: Intracerebral Gene Therapy for Sanfilippo Type A Syndrome
Official title: An Open-label, Single Arm, Monocentric, Phase I/II Clinical Study 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Mucopolysaccharidosis Type III A
Sanfilippo Disease Type A
Keywords: Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Gene Therapy
Adenovirus Associated Vector
Lead sponsor: LYSOGENE
Sponsor class: INDUSTRY
First posted: 2011-11-18
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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®

Primary outcomes:
measure: Tolerance and safety
timeFrame: during the one year follow-up
Secondary outcomes:
measure: To collect data to define exploratory tests that could become evaluation criteria for further clinical phase III efficacy studies
timeFrame: during the one year follow-up
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre - Assistance Publique des Hôpitaux de Paris
city: Paris
country: France
facility: Hôpital Necker, Assistance Publique des Hôpitaux de Paris
Study officials:
References: