Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

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.

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Key information

Conditions

Mucopolysaccharidosis Type III A Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis III Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases Sanfilippo Disease Type A Skin and Connective Tissue Diseases

Age range

18 month–6 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Hôpital Bicêtre - Assistance Publique des Hôpitaux de Paris, Le Kremlin-Bicêtre, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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®

Treatment and study plan

SAF-301

Genetic

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.

Primary outcomes

Tolerance and safety

Time frame: during the one year follow-up
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)

Secondary outcomes

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

Time frame: during the one year follow-up
- Brain MRI
- Neurocognitive/behavioral tests
- Biological markers on blood, urine and CSF

Sponsors and collaborators

Lead sponsor

LYSOGENE

Industry

Registry information

Official study 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.

Important dates

Study start: 2011
Primary completion: 2013
Study completion: 2013
First posted: Nov 18, 2011
Registry last updated: May 6, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed