Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA)

NCT03612869 | Unknown Phase 2 FDA Drug

• 1 other identifier: P4-SAF-302
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 8

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.

Conditions

Mucopolysaccharidosis Type IIIA

Keywords

MPS IIIA; Sanfilippo syndrome Type A; Mucopolysaccharidosis Type IIIA; Lysosomal Storage Disease

Outcome Measures

Primary Outcomes (1)

• Change from baseline in development quotient (DQ), compared to regression reported in natural history studies

  Development Quotient will be measured for each patient using one of two standard instruments, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II), based on age and ability range. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which is computed as a ratio and expressed as a percentage using the development age (DA) score divided by the age at testing (\[development age score/chronological age\] × 100; range: 0 - 100, where high values are desirable).

  Month 6, 12, 18, 24

Secondary Outcomes (6)

• Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II)

  Month 6, 12, 18, 24

• Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ)

  Month 6, 12, 18, 24

• Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire

  Month 12, 24

• Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)

  Month 12, 24

• Change from baseline in total cortical grey matter volume and white matter volume on MRI

  Month 12, 24

Study Arms (1)

AAV SGSH gene therapy (LYS-SAF302)

EXPERIMENTAL

One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA.

Drug: LYS-SAF302

Interventions

LYS-SAF302 DRUG

Treatment will involve direct injections of the investigational product into both sides of the brain through image-guided tracks, in a single neurosurgical session.

Also known as: AAVrh10-h.SGSH

AAV SGSH gene therapy (LYS-SAF302)

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• LYSOGENE: lead

Study Sites (8)

CHOC Children's

Orange, California, 92868, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Weill Cornell Medical College

New York, New York, 10065-4897, United States

Location

Baylor college of medicine / Texas children's hospital

Houston, Texas, 77030, United States

Location

Armand Trousseau Public Hospital

Paris, 75012, France

Location

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Amsterdam UMC

Amsterdam, 1000, Netherlands

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24524415 BACKGROUND

MeSH Terms

Conditions

Mucopolysaccharidosis III; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: August 2, 2018
• Study Start: December 17, 2018
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: August 31, 2021

Record last verified: 2021-08

Locations

GB (1); FR (1); US (4); DE (1); NL (1)