Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Mucopolysaccharidosis Type III A, Sanfilippo Disease Type A

Intervention / Treatment
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* Genetic: SAF-301


Participation Criteria
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Eligibility Criteria
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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®

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAF-301<br> | Genetic: SAF-301<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | during the one year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | during the one year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurodegenerative Diseases, Nervous System Diseases, Genetic Diseases, Inborn, Metabolic Diseases, Gene Therapy, Adenovirus Associated Vector