Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

Sanfilippo Syndrome B Clinical Trial

Official title:

Protocol AMT110-CD-001: A Phase I/II, Open-label, Study of Intracerebral Administration of Adeno-associated Viral Vector Containing the Human Alpha-N-acetylglucosaminidase cDNA in Children With Sanfilippo Type B Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03300453
• Other study ID #: AMT110-CD-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 17, 2013
• Est. completion date: November 27, 2019

Study information

• Verified date: October 2018
• Source: UniQure Biopharma B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: November 27, 2019
• Est. primary completion date: November 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 60 Months

Eligibility

Inclusion criteria:

• Age: 18 months up to 60 months (5th birthday);

• Onset of clinical manifestations related to mucopolysaccharidosis type IIIB (MPSIIIB);

• NAGLU activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls;

• Patient affiliated to, or covered by a French social security regimen, or European patients with European Health Insurance Card;

• Family understanding the procedure and the informed consent;

• Signed informed consent by both parents or legal representative;

• Vital laboratory parameters within normal range.

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®).

Related Conditions & MeSH terms

• Mucopolysaccharidosis III
• Sanfilippo Syndrome B
• Syndrome

Intervention

Drug:
• rAAV2/5-hNAGLU
one-time brain intraparenchymal gene therapy dose

Locations

Country	Name	City	State
France	Hopitaux Universitaires Paris-Sud	Paris	Le Kremlin-Bicetre Cedex

Sponsors (3)

Lead Sponsor	Collaborator
UniQure Biopharma B.V.	Institut Pasteur, Venn Life Sciences

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline	Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.	Baseline until end of study (Month 66)
Secondary	Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI	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.	Baseline until end of study (Month 66)