NCT03300453

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2013

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 17, 2013

Completed
2.7 years until next milestone

First Submitted

Initial submission to the registry

June 15, 2016

Completed
1.3 years until next milestone

First Posted

Study publicly available on registry

October 3, 2017

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 27, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 27, 2019

Completed
Last Updated

December 2, 2019

Status Verified

October 1, 2018

Enrollment Period

6.2 years

First QC Date

June 15, 2016

Last Update Submit

November 28, 2019

Conditions

Sanfilippo Syndrome B

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • 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)

Study Arms (1)

rAAV2/5-hNAGLU

EXPERIMENTAL

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

Interventions

rAAV2/5-hNAGLUDRUG

one-time brain intraparenchymal gene therapy dose

Also known as: AAV5
rAAV2/5-hNAGLU

Eligibility Criteria

Age18 Months - 60 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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®).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hopitaux Universitaires Paris-Sud

Paris, Le Kremlin-Bicetre Cedex, 94275, France

Location

Related Publications (1)

  • 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.

    PMID: 34040605DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis III

Condition Hierarchy (Ancestors)

MucopolysaccharidosesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLysosomal Storage DiseasesMucinosesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Kumaran Deiva, MD

    Hopitaux Universitaires Paris-Sud

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 15, 2016

First Posted

October 3, 2017

Study Start

September 17, 2013

Primary Completion

November 27, 2019

Study Completion

November 27, 2019

Last Updated

December 2, 2019

Record last verified: 2018-10

Locations

FR(1)