Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

• ClinicalTrials.gov Identifier: NCT01474343
• Recruitment Status: Completed
• First Posted: November 18, 2011
• Last Update Posted: May 6, 2014
• Sponsor: LYSOGENE
• Information provided by (Responsible Party): LYSOGENE

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis Type III A; Sanfilippo Disease Type A	Genetic: SAF-301	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: August 2011
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAF-301	Genetic: SAF-301; 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.

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Months to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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®

Contacts and Locations

Locations

France

Hôpital Bicêtre - Assistance Publique des Hôpitaux de Paris

Le Kremlin Bicêtre, France, 94275

Hôpital Necker, Assistance Publique des Hôpitaux de Paris

Paris, France, 75015

Sponsors and Collaborators

LYSOGENE

More Information

• Responsible Party: LYSOGENE
• ClinicalTrials.gov Identifier: NCT01474343
• Other Study ID Numbers: P1-SAF-301
• First Posted: November 18, 2011
• Last Update Posted: May 6, 2014
• Last Verified: May 2014

Keywords provided by LYSOGENE:

Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Gene Therapy; Adenovirus Associated Vector

Additional relevant MeSH terms:

Mucopolysaccharidoses; Mucopolysaccharidosis III; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases