MPS III
Conditions
Interventions
LYS-SAF302 is the adeno-associated viral vector serotype rh.10 (AAVrh.10)
carrying the human N-sulfoglucosamine sulfohydrolase (SGSH) gene (LYS-SAF302),
suspension for injection.
The level of residu
Sponsors
Blue Daisy
Eligibility
Age
No minimum to 11 Years
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 = 50% 4. Signed written informed consent before any study related procedure is performed 5. Medical status sufficiently stable, in the opinion of the investigator, to adhere to the study visit schedule and other protocol procedures 6. Confirmation by the study neurosurgeon and anesthesiologist of the feasibility of the neurosurgical procedure.
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 (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the observed (post-surgery) evolution of cognitive developmental quotient (DQ) expressed by the ratio (DQ24/DQ0) between baseline and 24 months. Actual values will be compared to the ones expected based on modeling from natural history studies. Cognitive DQ will be assessed by neurocognitive testing using the Bayley Scale for Infant and Toddler Development, 3rd Edition (BSIDIII) or the Kaufman Assessment Battery for Children, 2nd Edition (KABCII), depending on child's age and ability. Primary and secondary analyses will be performed separately on the main and the ancillary cohorts. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include: • The change from baseline in the cognitive developmental age (DA) and cognitive developmental quotient (DQ) assessed by neurocognitive tests (BSID III or KABC-II) at all timepoints • The change from baseline in other DA and DQ (language and motor) assessed by neurocognitive tests (BSID III or KABC-II) at all timepoints • The percentage of patients with stabilized developmental 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 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 CSF and PBMC | — |
Countries
Netherlands
Outcome results
None listed