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

LYSOGENE20 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mucopolysaccharidosis Type IIIA

Interventions

LYS-SAF302DRUG

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

Eligibility

Sex: ALLMin age: 6 Months

Medical Language ↔ Plain English

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.

Locations (8)

CHOC Children's

Orange, California, United States

University of Minnesota

Minneapolis, Minnesota, United States

Weill Cornell Medical College

New York, New York, United States

Baylor college of medicine / Texas children's hospital

Houston, Texas, United States

Outcomes

Primary Outcomes

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).

Time frame: Month 6, 12, 18, 24

Secondary Outcomes

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

The Vineland Adaptive Behavior Scales VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The VABS-II is a norm-based instrument, where the child's adaptive functioning is compared to that of others his or her age. The total adaptive behavior composite score describe the child's functioning. The normative mean score is 100 (normative standard deviation is 15). Higher scores indicate better functioning.

Time frame: Month 6, 12, 18, 24

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

The Children's Sleep habits Questionnaire (CSHQ) measures sleep habits and behavioral sleep disorders in preschool and school-aged children. The abbreviated CSHQ is a 23-item multiple-choice questionnaire that is summed into 8 subscales (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night waking, parasomnias, sleep-disordered breathing, and daytime sleepiness) and a CSHQ total score, where higher scores reflect greater disturbance in sleep pattern. Scores will be compared to scores from the Natural History control group, using the same tool and same timepoints.

Time frame: Month 6, 12, 18, 24

Data from ClinicalTrials.gov

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