Phase 1 study to evaluate safety and efficacy of BMN 190
Research type
Research Study
Full title
A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients with Neuronal Ceroid Lipofuscinosis CLN2 Disease
IRAS ID
124287
Contact name
Ruth Williams
Contact email
Eudract number
2012-005430-11
Research summary
Neuronal ceroid lipofuscinosis, CLN2 disease is a rare genetic neurodegenerative disease characterized by the deficiency of tripeptidyl peptidase 1 (TPP1) caused by mutations in the CLN2 gene. The absence of TPP1 results in the accumulation of abnormal storage material in many organs. Symptoms include seizures, movement disorder, dementia and visual loss. Death occurs in childhood and there is neither curative nor disease modifying treatment.
BMN 190 is a genetically engineered synthetic human TPP1. The primary goal of this study is to test the safety and efficacy of enzyme replacement therapy in CLN2 disease using this new medicinal product. Data regarding the efficacy of BMN 190 in altering the expected course of the disease will also be collected.
Following baseline evaluations including clinical examination, bloods tests, EEG, brain imaging and administration of quality of life questionnaires, a Rickham reservoir and intracerebro-ventricular catheter will be placed using standard neurosurgical techniques under general anaesthesia. BMN 190 will be administered alternate weeks by infusion through the reservoir into the lateral cerebral ventricle on the Paediatric Intensive Care or High Dependency Unit of Evelina Children's Hospital over at least 48 weeks. Children will be monitored carefully throughout the infusions, and blood and CSF samples will be taken for pharmocodynamic and pharmacokinetic studies. Children will undergo further clinical examinations, EEG and Brain MRI scans at 2-4 monthly intervals during the course of the study.
Because practical and ethical concerns preclude contemporaneous or untreated control subjects, findings will be compared with historical data from existing CLN2 clinical registries. The planned international enrolment for this study is 22 subjects over 2 European sites: Evelina Children's Hospital, London, and University Medical center Hamburg-Eppendorf in Germany.REC name
London - City & East Research Ethics Committee
REC reference
13/LO/0926
Date of REC Opinion
15 Aug 2013
REC opinion
Further Information Favourable Opinion