gene therapy for children with variant late infantile neuronal ceroid lipofuscinosis 6 (vlincl6) disease

Conditions: Variant Late-Infantile Neuronal Ceroid Lipofuscinosis

Summary: this is a phase 1/2, open-label, single dose study to evaluate the safety and efficacy of at-gtx-501 delivered intrathecally into the lumbar spinal cord region of participants with mild to moderate variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the cln6 gene (vlincl6 disease).

this is an open-label, single-dose study of at-gtx-501 administered by a single intrathecal injection. safety and efficacy are evaluated over a 2 year period. the efficacy assessments in this study are to evaluate motor, language, visual, and cognitive function, as well as survival and other outcome measures. participants are tested at baseline, receive at-gtx-501 on day 0, and return for visits on days 7, 14, 21, and 30, and then every 3 months until month 24. following completion of this study, there is a long-term follow up study in which data will continue to be collected (study at-gtx-501-02 / nct04273243). for more information about this study, please contact amicus therapeutics patient advocacy at clinicaltrials@amicusrx.com or +1 609-662-2000.

Eligibility criteria:
inclusion criteria: 1. diagnosis of vlincl6 disease determined by genotype available at screening 2. a score of ≥ 3 on the quantitative clinical assessment of the hamburg motor-language aggregate scale at screening 3. aged ≥ 1 year 4. ambulatory or able to walk with assistance exclusion criteria: 1. presence of another inherited neurologic disease, for example, other forms of batten disease (also known as ncl) or seizures unrelated to vlincl6 disease (participants with febrile seizures may be eligible at discretion of the investigator.) 2. presence of another neurological illness that may have caused cognitive decline (for example, trauma, meningitis, hemorrhage) before screening 3. active viral infection (includes human immunodeficiency virus or serology positive for hepatitis b or c) 4. has received stem cell or bone marrow transplantation for vlincl6 disease 5. contraindications for intrathecal administration of the product or lumbar puncture, such as bleeding disorders or other medical conditions (for example, spina bifida, meningitis, or clotting abnormalities) 6. contraindications for magnetic resonance imaging scans (for example, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain) 7. episode of generalized motor status epilepticus within 4 weeks before the gene transfer visit (visit 2) 8. severe infection (for example, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the gene transfer visit (visit 2) (enrollment may be postponed.) 9. has received any investigational medication within 30 days before the gene transfer visit (visit 2) 10. anti-aav9 antibody titers \> 1:50 as determined by enzyme-linked immunosorbent assay 11. has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the participant's ability to comply with the protocol-required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability 12. pregnancy any time during the study (any female participant judged by the investigator to be of childbearing potential will be tested for pregnancy.) 13. abnormal laboratory values from screening considered clinically significant (gamma glutamyl transferase \> 3 times the upper limit of normal, bilirubin ≥ 3.0 mg/dl, creatinine ≥ 1.8 mg/dl, hemoglobin \ 18 g/dl, white blood cells \> 15,000 per cmm) 14. family does not want to disclose participant's study participation with primary care physician and other medical providers. 15. history of or current chemotherapy, radiotherapy, or other immunosuppression therapy within the 30 days preceding screening (corticosteroid treatment may be permitted at the discretion of the investigator.) 16. has 2 consecutive abnormal liver tests at screening (\> 2 times the upper limit of normal). liver enzymes will be re-tested once if abnormal upon initial screening.

Keywords: neuronal ceroid lipofuscinosis (ncl) cln6 vlincl6 gene transfer cln6 batten disease batten disease