Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
LYSOGENE
ClinicalTrials.gov Identifier:
NCT01474343
First received: November 10, 2011
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Mucopolysaccharidosis Type III A
Sanfilippo Disease Type A
Genetic: SAF-301
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by LYSOGENE:

Primary Outcome Measures:
  • Tolerance and safety [ Time Frame: during the one year follow-up ] [ Designated as safety issue: Yes ]

    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:
  • 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 ] [ Designated as safety issue: No ]
    • Brain MRI
    • Neurocognitive/behavioral tests
    • Biological markers on blood, urine and CSF


Enrollment: 4
Study Start Date: August 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Months to 6 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01474343

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

Additional Information:
No publications provided

Responsible Party: LYSOGENE
ClinicalTrials.gov Identifier: NCT01474343     History of Changes
Other Study ID Numbers: P1-SAF-301
Study First Received: November 10, 2011
Last Updated: May 5, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

ClinicalTrials.gov processed this record on July 24, 2014