Clinical trial NCT03612869: Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA)
Official title: Open-label, Single-arm, Multi-center Study of Intracerebral Administration of Adeno-associated Viral (AAV) Serotype rh.10 Carrying Human N-sulfoglucosamine Sulfohydrolase (SGSH) cDNA for Treatment of Mucopolysaccharidosis Type IIIA
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Mucopolysaccharidosis Type IIIA
Keywords: MPS IIIA
Sanfilippo syndrome Type A
Mucopolysaccharidosis Type IIIA
Lysosomal Storage Disease
Lead sponsor: LYSOGENE
Sponsor class: INDUSTRY
First posted: 2018-08-02
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: MPS IIIA is predominantly a central nervous system disease causing cognitive disability, progressive loss of acquired skills, behavioral and sleep disturbance. LYS-SAF302 is a gene therapy which is intended to deliver a functional copy of the SGSH gene to the brain. This is a phase 2-3 study to assess the efficacy in improving or stabilizing the neurodevelopmental state of MPS IIIA patients.

Detailed description: The study is interventional, single arm and multi-center. Evolution under treatment will be compared to expected natural evolution based on natural history studies.

Eligibility criteria: Inclusion Criteria:

* Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
* Cognitive DQ score on BSID-III: 50% and above

Exclusion Criteria:

* Homozygous for the S298P mutation or non-classical severe form of MPS IIIA, based on investigator's judgement.
* Participation in another gene or cell therapy clinical trial.
* Past use of SGSH enzyme replacement therapy for a period exceeding 3 months. A washout period of at least 2 months is required prior to screening.
* Current participation in a clinical trial of another investigational medicinal product.
* History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following surgery.
* Any condition that would contraindicate treatment with immunosuppressants such as tacrolimus, mycophenolate mofetil or steroids.

Primary outcomes:
measure: Change from baseline in development quotient (DQ), compared to regression reported in natural history studies
timeFrame: Month 6, 12, 18, 24
Secondary outcomes:
measure: Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II)
timeFrame: Month 6, 12, 18, 24
measure: Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ)
timeFrame: Month 6, 12, 18, 24
measure: Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire
timeFrame: Month 12, 24
measure: Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)
timeFrame: Month 12, 24
measure: Change from baseline in total cortical grey matter volume and white matter volume on MRI
timeFrame: Month 12, 24
measure: Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study
timeFrame: Month 24
Other outcomes:
Locations:
city: Orange
country: United States
facility: CHOC Children's
state: California
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Houston
country: United States
facility: Baylor college of medicine / Texas children's hospital
state: Texas
city: Paris
country: France
facility: Armand Trousseau Public Hospital
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
References:
citation: Tardieu M, Zerah M, Husson B, de Bournonville S, Deiva K, Adamsbaum C, Vincent F, Hocquemiller M, Broissand C, Furlan V, Ballabio A, Fraldi A, Crystal RG, Baugnon T, Roujeau T, Heard JM, Danos O. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. Hum Gene Ther. 2014 Jun;25(6):506-16. doi: 10.1089/hum.2013.238. Epub 2014 May 5.