Mucopolysaccharidosis Type IIIA MedDRA version: 20.1 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: LYS-SAF302
Product Code: LYS-SAF302
Pharmaceutical Form: Injection
INN or Proposed INN: OLENASUFLIGENE RELDUPARVOVEC
Current Sponsor code: LYS-SAF302
Other descriptive name: LYS-SAF302
C
Sponsors
Lysogene SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations 2. Age = 30 months at screening (main cohort) or =6 months and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Homozygous for the S298P mutation or non-severe form of MPS IIIA, based on investigator’s judgement 2. Past participation in another gene or cell therapy clinical trial 3. Past use of SGSH enzyme replacement therapy for a cumulative period exceeding 3 months. In addition, a washout period of at least 2 months is required prior to screening 4. Current participation in a clinical trial of another investigational medicinal product. NOTE: Nutritional supplements, including Genistein are permitted if they are taken outside the context of an investigational trial 5. History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following surgery 6. Presence of concomitant medical condition precluding lumbar puncture 7. Presence of any item (e.g., metal braces) precluding undergoing MRI 8. Any condition that would contraindicate treatment with immunosuppressants such as tacrolimus, mycophenolate mofetil or steroids 9. History of significant non-MPS IIIA related CNS impairment or behavioral disturbances that would confound scientific rigor or interpretation of results 10. Rare and unrelated serious comorbidities (e.g. Down syndrome), intraventricular hemorrhage in the new-born period, or extreme low birth weight (<1500 grams) 11. History of poorly controlled seizure disorder 12. Any vaccination 1 month prior to the planned surgery 13. Serology consistent with HIV exposure or consistent with active hepatitis B or C infection 14. Grade 2 or higher lab abnormalities for LFT, bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT, and a PTT 15. Visual or hearing impairment sufficient, in the clinical judgment of the investigator, to preclude cooperation with neurodevelopmental testing. Use of hearing aids is permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of intracerebral delivery of AAVrh.10SGSH gene therapy (LYS-SAF302) in improving or stabilizing the neurodevelopmental status of MPS IIIA patients after 24 months (main cohort), compared to the expected evolution based on natural history data.;Secondary Objective: To assess the safety and tolerability of intracerebral delivery of LYS-SAF302 and to assess the treatment efficacy on the behavioral, sleep disturbances of the patients, treatment effect on brain imaging, biomarkers and on quality of life for both patient and parents.;Primary end point(s): The primary efficacy measurement is the comparison between the observed (post-surgery) evolution of cognitive development quotient (DQ) expressed by the ratio (DQ24/DQ0) between baseline and 24 months and the expected ratio calculated by applying a regression coefficient based on data from natural history studies. Cognitive DQ will be assessed by neurocognitive testing using the Bayley Scale for Infant and Toddler Development, 3rd Edition (BSID-III) or the Kauffman Assessment Battery for Children , 2nd Edition (KABC-II), depending on child’s age and ability. Primary and secondary analyses will be performed separately on the main and the ancillary cohorts.;Timepoint(s) of evaluation of this end point: Primary endpoint between baseline and 24 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The change from baseline in the cognitive development age (DA) and cognitive development quotient (DQ) assessed by neurocognitive tests (BSID III or KABCII) at all timepoints - The change from baseline in other DA and DQ (language and motor) assessed byneurocognitive tests (BSID III or KABC-II) at all timepoints -The percentage of patients with at least stabilized development age (DA) at 12 months and 24 months - The change from baseline in the total adaptive behavior composite standard score as measured by the Vineland Adaptive Behavior Scales (VABS-II) at 12 months and 24 months and change from baseline in total behavior problem as measured by the Child Behavior Checklist (CBCL) at 12 and 24 months - The change from baseline in sleep pattern as measured by the Children Sleep Habits Questionnaire (CSHQ) at 12 months and 24 months - The change from baseline in the patient/parent quality of life - The change from baseline in total cortical grey matter volume and white matter volume on MRI at 12 months and 24 months - The change from baseline in relevant disease biomarkers in serum, CSF and urine;Timepoint(s) of evaluation of this end point: BSID III, KABC-II and biomarkers will be assessed at all timepoints DA, VABS-II, CBCL, CSHQ, ITQOL-SF47, GHQ, HUI-3, PSI-4-SF, MRI at 12 and 24 months for the main cohort. Corresponding timepoint of primary interest for the young cohort will be when all patients from the young cohort have reached 4 years of age. | — |
Countries
France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactSophie Olivier
Lysogene SA
Outcome results
None listed