Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

Phase 1

Completed

• Conditions: Sanfilippo Syndrome B
• Interventions: Drug: rAAV2/5-hNAGLU

• Registration Number: NCT03300453
• Lead Sponsor: UniQure Biopharma B.V.

Brief Summary

This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.

Detailed Description

This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.

Four patients, 18 months up to the 5th birthday, have been included.

The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1 year post-surgery. The duration of the first extension phase is 18 months. The duration of the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be 66 months

Study Timeline

• Study Start: 2013-09-17
• Study First Submitted: 2016-06-15
• Study First Submitted QC: 2017-10-02
• Study First Posted: 2017-10-03
• Status Verified: 2018-10
• Primary Completion: 2019-11-27
• Study Completion: 2019-11-27
• Last Update Submitted: 2019-11-28
• Last Update Posted: 2019-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

• Presence of brain atrophy on baseline MRI judged on a cortico-dural distance of more than 0.6 cm;
• Any condition that would contraindicate general anesthesia;
• Any other permanent medical condition not related to MPSIIIB that could contraindicate the study participation;
• No independent walking (ability to walk without help);
• Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection (sleep and mood regulators are accepted);
• Any condition that would contraindicate treatment with Modigraf®, Cellcept® and prednisolone (Solupred® and Solumedrol®).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rAAV2/5-hNAGLU	rAAV2/5-hNAGLU	Each patient will receive 960 µL of vector suspension. The vector suspension will be deposited simultaneously at 16 sites, each deposit containing 2.4x 1011 vg (4x1012 vg in total).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline	Baseline until end of study (Month 66)	Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI	Baseline until end of study (Month 66)	MRIs at Baseline, Month 3, Month 12, Month 30, Month 48 and last visit Month 66.; Cerebral MRI will be collected for safety assessment to retrospectively evaluate for efficacy at Baseline, D0, Month 3, Month12, Month 30 and last visit Month 66.

Trial Locations

Locations (1)

Hopitaux Universitaires Paris-Sud; 🇫🇷 Paris, Le Kremlin-Bicetre Cedex, France