AN OPEN-LABEL, SINGLE ARM, MONOCENTRIC, PHASE I/II CLINICAL STUDY OF INTRACEREBRAL ADMINISTRATION OF ADENO-ASSOCIATED VIRAL VECTORS SEROTYPE 10 CARRYING THE HUMAN SGSH AND SUMF1 cDNAS FOR THE TREATMENT OF SANFILIPPO TYPE A SYNDROME - Intracerebral Gene therapy for Sanfilippo type A syndrome

• Register: EUCTR
• Last refreshed on: 19 May 2014
• Main ID: EUCTR2010-019962-10-FR
• Date of registration: 19/11/2010
• Prospective Registration: Yes
• Primary sponsor: SANFILIPPO Therapeutics SAS
• Public title: AN OPEN-LABEL, SINGLE ARM, MONOCENTRIC, PHASE I/II CLINICAL STUDY OF INTRACEREBRAL ADMINISTRATION OF ADENO-ASSOCIATED VIRAL VECTORS SEROTYPE 10 CARRYING THE HUMAN SGSH AND SUMF1 cDNAS FOR THE TREATMENT OF SANFILIPPO TYPE A SYNDROME - Intracerebral Gene therapy for Sanfilippo type A syndrome
• Scientific title: AN OPEN-LABEL, SINGLE ARM, MONOCENTRIC, PHASE I/II CLINICAL STUDY OF INTRACEREBRAL ADMINISTRATION OF ADENO-ASSOCIATED VIRAL VECTORS SEROTYPE 10 CARRYING THE HUMAN SGSH AND SUMF1 cDNAS FOR THE TREATMENT OF SANFILIPPO TYPE A SYNDROME - Intracerebral Gene therapy for Sanfilippo type A syndrome
• Target sample size: 4
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019962-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France

Key inclusion & exclusion 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 social security
• Family understanding the procedure and the informed consent
• Signed informed consent
• Vital laboratory parameters within normal range

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Presence of brain atrophy on pre-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 treatment
• Receipt 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®, Cellcept® and Solupred®



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Sanfilippo type A syndrome (also named Mucopolysaccharidosis Type A)
MedDRA version: 12.1 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome

Intervention(s)

Product Name: AAVrh.10-hMPSIIIA
Product Code: SAF-301
Pharmaceutical Form: Solution for injection

Primary Outcome(s)

Main Objective: To assess the tolerance and safety associated to the proposed treatment through a one-year follow up.

Primary end point(s): The safety parameters that will be evaluated are:
• Clinical parameters:
- during the 15 days after vector injection: fever (>38°C), seizure (anytype), headache (grade 3 or more on the pain scale), abnormal somnolence or lethargy, any new unexpected neurological symptoms
- during the one year follow-up: any infectious disease, any new neurological symptom, any liver, spleen or lymph node enlargement, any aphtous lesion, any chronic respiratory symptoms, any abnormal bleeding or paetechia
- after the one year protocol: any unexpected neurological or extra-neurological symptoms including malignancies.
• Radiological parameters:
- on the initial CT scan after surgery: any sign of bleeding
- on subsequent MRI: any hypersignal on T2 weighted images or diffusion images that are not at the points of injection, any necrotic area evaluated through T1-weighted and diffusion imaging as well as modification of lipids in spectroscopy
• Biological parameters: Parameters listed in sections Haematology and Biochemistry §3.2.2.3. In particular: anemia (<8 g/L haemoglobin), leucopenia (<1000 leucocytes/ml)), thrombopenia (< 100000 platelets/ml), liver dysfunction (>X3 normal for transaminases).

Secondary Objective: To collect data to define exploratory tests that could become evaluation criteria for further clinical phase III efficacy studies (Brain MRI, neuro- and psychological tests and biological markers)

Secondary ID(s)

P1-SAF301