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Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

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ClinicalTrials.gov Identifier: NCT03300453
Recruitment Status : Active, not recruiting
First Posted : October 3, 2017
Last Update Posted : October 11, 2018
Sponsor:
Collaborators:
Venn Life Sciences
Institut Pasteur
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Sanfilippo Syndrome B Drug: rAAV2/5-hNAGLU Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2013
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019


Arm Intervention/treatment
Experimental: 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).
Drug: rAAV2/5-hNAGLU
one-time brain intraparenchymal gene therapy dose
Other Name: AAV5




Primary Outcome Measures :
  1. Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline [ Time Frame: 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 :
  1. Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI [ Time Frame: 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.




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Ages Eligible for Study:   18 Months to 60 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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®).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03300453


Locations
France
Hopitaux Universitaires Paris-Sud
Paris, Le Kremlin-Bicetre Cedex, France, 94275
Sponsors and Collaborators
UniQure Biopharma B.V.
Venn Life Sciences
Institut Pasteur
Investigators
Principal Investigator: Kumaran Deiva, MD Hopitaux Universitaires Paris-Sud

Responsible Party: UniQure Biopharma B.V.
ClinicalTrials.gov Identifier: NCT03300453     History of Changes
Other Study ID Numbers: AMT110-CD-001
First Posted: October 3, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Mucopolysaccharidosis III
Syndrome
Disease
Pathologic Processes
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases