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Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

Primary Purpose

Mucopolysaccharidosis Type III A, Sanfilippo Disease Type A

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

SAF-301

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis Type III A focused on measuring Neurodegenerative Diseases, Nervous System Diseases, Genetic Diseases, Inborn, Metabolic Diseases, Gene Therapy, Adenovirus Associated Vector

Eligibility Criteria

18 Months - 6 Years (Child)All SexesDoes not accept healthy volunteers

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®

Sites / Locations

Hôpital Bicêtre - Assistance Publique des Hôpitaux de Paris
Hôpital Necker, Assistance Publique des Hôpitaux de Paris

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SAF-301

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01474343

First Posted

November 10, 2011

Last Updated

May 5, 2014

Sponsor

LYSOGENE

1. Study Identification

Unique Protocol Identification Number

NCT01474343

Brief Title

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

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

LYSOGENE

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mucopolysaccharidosis Type III A, Sanfilippo Disease Type A

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SAF-301

Arm Type

Experimental

Intervention Type

Genetic

Intervention Name(s)

SAF-301

Intervention Description

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 Outcome Measure Information:

Title

Tolerance and safety

Description

Time Frame

during the one year follow-up

Secondary Outcome Measure Information:

Title

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

Description

Brain MRI Neurocognitive/behavioral tests Biological markers on blood, urine and CSF

Time Frame

during the one year follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Months

Maximum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

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®

Facility Information:

Facility Name

Hôpital Bicêtre - Assistance Publique des Hôpitaux de Paris

City

Le Kremlin Bicêtre

ZIP/Postal Code

94275

Country

France

Facility Name

Hôpital Necker, Assistance Publique des Hôpitaux de Paris

City

Paris

ZIP/Postal Code

75015

Country

France

12. IPD Sharing Statement

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Intracerebral Gene Therapy for Sanfilippo Type A Syndrome

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