Back to resultsStudy of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA) (AAVance)
Primary Purpose
Mucopolysaccharidosis Type IIIA
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LYS-SAF302
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis Type IIIA focused on measuring MPS IIIA, Sanfilippo syndrome Type A, Mucopolysaccharidosis Type IIIA, Lysosomal Storage Disease
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.
Sites / Locations
- CHOC Children's
- University of Minnesota
- Weill Cornell Medical College
- Baylor college of medicine / Texas children's hospital
- Armand Trousseau Public Hospital
- University Medical Center Hamburg-Eppendorf
- Amsterdam UMC
- Great Ormond Street Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AAV SGSH gene therapy (LYS-SAF302)
Arm Description
One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
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.
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.
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03612869
Brief Title
Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA)
Acronym
AAVance
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
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 17, 2018 (Actual)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
March 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LYSOGENE
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis Type IIIA
Keywords
MPS IIIA, Sanfilippo syndrome Type A, Mucopolysaccharidosis Type IIIA, Lysosomal Storage Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AAV SGSH gene therapy (LYS-SAF302)
Arm Type
Experimental
Arm Description
One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA.
Intervention Type
Drug
Intervention Name(s)
LYS-SAF302
Other Intervention Name(s)
AAVrh10-h.SGSH
Intervention Description
Treatment will involve direct injections of the investigational product into both sides of the brain through image-guided tracks, in a single neurosurgical session.
Primary Outcome Measure Information:
Title
Change from baseline in development quotient (DQ), compared to regression reported in natural history studies
Description
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 Outcome Measure Information:
Title
Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II)
Description
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
Title
Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ)
Description
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
Title
Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire
Description
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.
Time Frame
Month 12, 24
Title
Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)
Description
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.
Time Frame
Month 12, 24
Title
Change from baseline in total cortical grey matter volume and white matter volume on MRI
Description
The change from baseline in grey matter and white matter volume will be assessed by magnetic resonance imaging (MRI)
Time Frame
Month 12, 24
Title
Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study
Description
Descriptive summary tables for the surgical period, the evaluation period, and the follow-up period will be provided.
Time Frame
Month 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
CHOC Children's
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065-4897
Country
United States
Facility Name
Baylor college of medicine / Texas children's hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Armand Trousseau Public Hospital
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
University Medical Center Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1000
Country
Netherlands
Facility Name
Great Ormond Street Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24524415
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.
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Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA)
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