An open-label, single-arm, multicenter study of intracerebral administration of adeno-associated viral vectors serotype rh.10 carrying the human N-sulfoglycosamine sulfohydrolase (SGSH) cDNA for the treatment of mucopolysaccharidosis type IIIA (MPS IIIA)
- Conditions
- 10057167MPS III10027424Sanfilippo syndrome
- Registration Number
- NL-OMON52445
- Lead Sponsor
- ysogene SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
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 < 30 months
(ancillary cohort)
3. Cognitive DQ score on BSID-III >= 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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the observed (post-surgery) evolution of cognitive<br /><br>developmental quotient (DQ) expressed by the ratio (DQ24/DQ0) between baseline<br /><br>and 24 months. Actual values will be compared to the ones expected based on<br /><br>modeling from natural history studies. Cognitive DQ will be assessed by<br /><br>neurocognitive testing using the Bayley Scale for Infant and Toddler<br /><br>Development, 3rd Edition (BSIDIII) or the Kaufman Assessment Battery for<br /><br>Children, 2nd Edition (KABCII), depending on child's age and ability. Primary<br /><br>and secondary analyses will be performed separately on the main and the<br /><br>ancillary cohorts.</p><br>
- Secondary Outcome Measures
Name Time Method