Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA) (AAVance)
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|ClinicalTrials.gov Identifier: NCT03612869|
Recruitment Status : Active, not recruiting
First Posted : August 2, 2018
Last Update Posted : August 31, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Mucopolysaccharidosis Type IIIA||Drug: LYS-SAF302||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||December 17, 2018|
|Estimated Primary Completion Date :||March 2022|
|Estimated Study Completion Date :||March 2022|
Experimental: AAV SGSH gene therapy (LYS-SAF302)
One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA.
Treatment will involve direct injections of the investigational product into both sides of the brain through image-guided tracks, in a single neurosurgical session.
Other Name: AAVrh10-h.SGSH
- Change from baseline in development quotient (DQ), compared to regression reported in natural history studies [ Time Frame: Month 6, 12, 18, 24 ]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).
- Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II) [ Time Frame: Month 6, 12, 18, 24 ]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.
- Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ) [ Time Frame: Month 6, 12, 18, 24 ]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.
- Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire [ Time Frame: Month 12, 24 ]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.
- Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4) [ Time Frame: Month 12, 24 ]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.
- Change from baseline in total cortical grey matter volume and white matter volume on MRI [ Time Frame: Month 12, 24 ]The change from baseline in grey matter and white matter volume will be assessed by magnetic resonance imaging (MRI)
- Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study [ Time Frame: Month 24 ]Descriptive summary tables for the surgical period, the evaluation period, and the follow-up period will be provided.
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|Ages Eligible for Study:||6 Months and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
- Cognitive DQ score on BSID-III: 50% and above
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03612869
|United States, California|
|Orange, California, United States, 92868|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10065-4897|
|United States, Texas|
|Baylor college of medicine / Texas children's hospital|
|Houston, Texas, United States, 77030|
|Armand Trousseau Public Hospital|
|Paris, France, 75012|
|University Medical Center Hamburg-Eppendorf|
|Hamburg, Germany, 20246|
|Amsterdam, Netherlands, 1000|
|Great Ormond Street Hospital|
|London, United Kingdom|
|Other Study ID Numbers:||
|First Posted:||August 2, 2018 Key Record Dates|
|Last Update Posted:||August 31, 2021|
|Last Verified:||August 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Undecided|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Sanfilippo syndrome Type A
Mucopolysaccharidosis Type IIIA
Lysosomal Storage Disease
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases