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Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

Primary Purpose

Sanfilippo Syndrome B

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
rAAV2/5-hNAGLU
Sponsored by
UniQure Biopharma B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sanfilippo Syndrome B

Eligibility Criteria

18 Months - 60 Months (Child)All SexesDoes not accept healthy volunteers

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®).

Sites / Locations

  • Hopitaux Universitaires Paris-Sud

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rAAV2/5-hNAGLU

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 15, 2016
Last Updated
November 28, 2019
Sponsor
UniQure Biopharma B.V.
Collaborators
Venn Life Sciences, Institut Pasteur
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1. Study Identification

Unique Protocol Identification Number
NCT03300453
Brief Title
Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
September 17, 2013 (Actual)
Primary Completion Date
November 27, 2019 (Actual)
Study Completion Date
November 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UniQure Biopharma B.V.
Collaborators
Venn Life Sciences, Institut Pasteur

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

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

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
rAAV2/5-hNAGLU
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
rAAV2/5-hNAGLU
Other Intervention Name(s)
AAV5
Intervention Description
one-time brain intraparenchymal gene therapy dose
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline
Description
Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.
Time Frame
Baseline until end of study (Month 66)
Secondary Outcome Measure Information:
Title
Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI
Description
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.
Time Frame
Baseline until end of study (Month 66)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
60 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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®).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kumaran Deiva, MD
Organizational Affiliation
Hopitaux Universitaires Paris-Sud
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopitaux Universitaires Paris-Sud
City
Paris
State/Province
Le Kremlin-Bicetre Cedex
ZIP/Postal Code
94275
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
34040605
Citation
Gougeon ML, Poirier-Beaudouin B, Ausseil J, Zerah M, Artaud C, Heard JM, Deiva K, Tardieu M. Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome. Front Immunol. 2021 May 10;12:655478. doi: 10.3389/fimmu.2021.655478. eCollection 2021.
Results Reference
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Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

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