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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHOC Children's | Orange | California | 92868 | United States | ||
| University of Minnesota |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24524415 | Background | 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. |
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| ID | Term |
|---|---|
| D009084 | Mucopolysaccharidosis III |
| D016464 | Lysosomal Storage Diseases |
| ID | Term |
|---|---|
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
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|
| 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. | Month 6, 12, 18, 24 |
| Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire | The 47-item ITQOL questionnaire assesses physical, mental, and social well-being of the child and the quality of life of parent/caregiver. Scores range from 0 to 100, where higher scores reflect better quality of life. Change in score from baseline will be compared to scores from the Natural History control group, using the same tool and same timepoints. | Month 12, 24 |
| Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4) | The 36-item questionnaire (PSI-4) is used to identify parent-child problem areas, measuring 3 main domains (parental distress, parent-child dysfunctional interaction, and difficult child), which all combined form a total stress score. Higher scores reflect a higher level of stress. Change in score from baseline will be compared to scores from the Natural History control group, using the same tool and same timepoints. | Month 12, 24 |
| Change from baseline in total cortical grey matter volume and white matter volume on MRI | The change from baseline in grey matter and white matter volume will be assessed by magnetic resonance imaging (MRI) | Month 12, 24 |
| Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study | Descriptive summary tables for the surgical period, the evaluation period, and the follow-up period will be provided. | Month 24 |
| Minneapolis |
| Minnesota |
| 55455 |
| United States |
| Weill Cornell Medical College | New York | New York | 10065-4897 | United States |
| Baylor college of medicine / Texas children's hospital | Houston | Texas | 77030 | United States |
| Armand Trousseau Public Hospital | Paris | 75012 | France |
| University Medical Center Hamburg-Eppendorf | Hamburg | 20246 | Germany |
| Amsterdam UMC | Amsterdam | 1000 | Netherlands |
| Great Ormond Street Hospital | London | United Kingdom |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |