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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 : Not yet recruiting
First Posted : August 2, 2018
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
LYSOGENE

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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type IIIA Drug: LYS-SAF302 Phase 2 Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022


Arm Intervention/treatment
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.
Drug: LYS-SAF302
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




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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)

  6. 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
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.

Information from the National Library of Medicine

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


Contacts
Contact: Lysogene trial inquiries +33 (0) 1 41 43 03 90 patientadvocacy@lysogene.com

Locations
United States, California
CHOC Children's Not yet recruiting
Orange, California, United States, 92868
Contact: Nina Movsesyan       nmovsesyan@choc.org   
Principal Investigator: Raymond Wang, MD         
United States, Minnesota
University of Minnesota Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Brenda Diethelm-Okita, MPA    612-625-1594    dieth001@umn.edu   
Principal Investigator: Chester Whitley, MD         
United States, New York
Weill Cornell Medical College Not yet recruiting
New York, New York, United States, 10065-4897
Contact: Department of Genetic Medicine    646-962-2672    cora@med.cornell.edu   
United States, Texas
Baylor college of medicine / Texas children's hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Lisa Emrick, MD    832-825-1717    emrick@bcm.edu   
France
Armand Trousseau Public Hospital Not yet recruiting
Paris, France, 75012
Contact: Bénédicte Heron, MD       benedicte.heron@aphp.fr   
Principal Investigator: Bénédicte Heron, MD         
Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
Netherlands
Amsterdam UMC Not yet recruiting
Amsterdam, Netherlands, 1000
Contact       e.tump@amc.uva.nl   
Principal Investigator: Frits Wijburg, MD         
Sponsors and Collaborators
LYSOGENE

Publications:
Responsible Party: LYSOGENE
ClinicalTrials.gov Identifier: NCT03612869     History of Changes
Other Study ID Numbers: P4-SAF-302
First Posted: August 2, 2018    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018
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

Keywords provided by LYSOGENE:
MPS IIIA
Sanfilippo syndrome Type A
Mucopolysaccharidosis Type IIIA
Lysosomal Storage Disease

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases