gene therapy for children with cln3 batten disease

Conditions: CLN3; Batten Disease

Summary: this is a phase 1/2, open-label, single dose, dose-escalation clinical trial to evaluate the safety and efficacy of at-gtx-502 (previous nch code: scaav9.p546.cln3) delivered intrathecally into the lumbar spinal cord region of subjects with cln3 batten disease.

this is a phase 1/2, open-label, single-dose, dose-escalation study of at-gtx-502 administered intrathecally into the lumbar spinal cord region of pediatric patients with cln3 batten disease. this study consists of a one-time injection of at-gtx-502 with follow-up visits on day 7, 14, 21, and 30, followed by every 3 months through 1 year post-dose, and then every 6 months through the fifth year. there are two cohorts with a low dose and a high dose. the primary outcome for this clinical study is to evaluate safety. the co-primary objective is to determine the efficacy of at-gtx-502 as measured by united batten disease rating scale (ubdrs) physical subscale. the secondary outcome measures include pediatric quality of life (pedsql) inventory, seizure subscale of the ubdrs and global impression subscale of the ubdrs. the exploratory outcome measures include visual impairment assessment, cognitive evaluations, brain magnetic resonance imaging (mri), electroencephalogram (eeg), electrocardiogram (ecg) and echocardiogram (echo). 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 cln3 batten disease determined by genotype available at screening by a college of american pathologists/clinical laboratory improvement amendments (cap/clia)-certified laboratory (or a non-us laboratory with an equivalent national accreditation/certification) 2. aged ≥ 3 to \< 11 years 3. ubdrs physical impairment score of ≤ 7 4. able to walk independently at least 50 feet exclusion criteria 1. presence of another inherited neurologic or metabolic disease, eg, other forms of batten disease (also known as neuronal ceroid lipofuscinosis; ncl) or seizures unrelated to cln3 batten disease (subjects with febrile seizures may be eligible at the discretion of the investigator) 2. presence of another neurological illness that may have caused cognitive decline (eg, trauma, meningitis, hemorrhage) before screening 3. active viral infection (includes hiv or serology positive for hepatitis b or c) 4. subjects with 2 consecutive aminotransaminase liver tests \> 3 times the upper limit of normal or \> 1.5 times the upper limit of normal if taking valproic acid at visit 1 (screening/baseline) 5. subjects with anti-aav9 antibody titers \> 1:400 as determined by elisa (enzyme-linked immunosorbent assay) binding immunoassay 6. abnormal laboratory values considered clinically significant 7. presence of immunologic disease 8. has received stem cell or bone marrow transplantation 9. has received any form of organ transplant 10. history of or current chemotherapy, radiotherapy, or other immunosuppression therapy within the past 30 days (corticosteroid treatment may be permitted at the discretion of the investigator) 11. current use of cannabinoids and any by-products 12. contraindications for intrathecal administration of the product or lumbar puncture (for collection of csf), such as bleeding disorders or other medical conditions (eg, spina bifida, meningitis, or clotting abnormalities) 13. contraindications for mri scans (eg, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain) 14. poorly controlled seizures - intractable epilepsy 15. episode of generalized motor status epilepticus within 4 weeks before the gene transfer visit 16. history of corneal or intraocular surgery 17. severe infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the gene transfer visit (enrollment may be postponed.) 18. has received any investigational medication within 30 days before the infusion of study drug 19. has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability 20. pregnancy at screening or day 0. any female subject judged by the investigator to be of childbearing potential will be tested for pregnancy. 21. family does not want to disclose subject's study participation with primary care physician and other medical providers

Keywords: cln3 neuronal ceroid lipofuscinosis ncl gene transfer