Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2). MedDRA version: 18.0 Level: LLT Classification code 10052074 Term: Neuronal ceroid lipofuscinosis NOS System Organ Class: 100000004850
Conditions
Interventions
Product Name: N/A
Product Code: BMN 190
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: cerliponase alfa
CAS Number: 151
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Has a diagnosis of CLN2 determined by TPP1 enzyme activity (dried blood spot) available at study entry. If no genotype information is available, blood will be collected for CLN2 gene analysis at baseline. In addition, blood for TPP1 enzyme activity (dried blood spot) will be collected at baseline to be analyzed centrally • Has mild to moderate disease documented by a two-domain score of 3-6 on motor/gait and language domains of the Hamburg Scale, with a score of at least 1 in each of these two domains • Written informed consent from parent or legal guardian and assent from subject, if appropriate • Has the ability to comply with protocol requirements, in the opinion of the investigator • Seizures are stable in the judgment of the investigator Are the trial subjects under 18? yes Number of subjects for this age range: 24 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Is less than 3 years old at enrollment • Has another inherited neurologic disease, e.g. other forms of CLN or seizures unrelated to CLN2 (patients with febrile seizures may be eligible) • Has another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) before study entry • Requires ventilation support, except for noninvasive support at night • Has received stem cell, gene therapy, or ERT for CLN2 • Has contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities) • Has contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain) • Has generalized motor status epilepticus within 4 weeks before the First Dose visit, taking care that status epilepticus is on clinical examination and not only electroencephalogram (EEG) (enrollment may be postponed) • Has severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the First Dose visit (enrollment may be postponed) • Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts • Has known hypersensitivity to any of the components of BMN 190 • Has received any investigational medication within 30 days before the first infusion of study drug or is scheduled to receive any investigational drug other than BMN 190 during the course of the study • 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 requirements or compromise the subject’s well being, safety, or clinical interpretability
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study include the following: • to evaluate safety and tolerability of BMN 190 administered to subjects with CLN2 by an implanted intracerebroventricular (ICV) reservoir and cannula • to evaluate effectiveness using a CLN2-specific rating scale score in comparison with natural history data after 12 months of treatment ; Secondary Objective: Secondary objectives of this study include the following: • to evaluate the impact of treatment on measurement of brain atrophy in comparison with NCL-2 natural history data after 12 months of treatment • to characterize single- and repeated-dose pharmacokinetics (PK) in cerebrospinal fluid (CSF) and plasma • to determine immunogenicity in CSF and serum ; Primary end point(s): The primary points of this study include the following: • to evaluate safety and tolerability of BMN 190 administered to subjects with CLN2 by an implanted intracerebroventricular (ICV) reservoir and cannula • to evaluate effectiveness using a CLN2-specific rating scale score in comparison with natural history data after 12 months of treatment ;Timepoint(s) of evaluation of this end point: Safety and tolerability reviews will occur during and following each dose until the end of the study. Efficacy will be evaluated at the first dose, every month during dose escalation and every two months during the stable dose period until the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints of this study include the following: • to evaluate the impact of treatment on measurement of brain atrophy in comparison with CLN2 natural history data after 12 months of treatment ;Timepoint(s) of evaluation of this end point: Neuroimaging (MRI) will be recorded before the first infusion (baseline), following the first dose, every two months during Dose Escalation, at months 2, 4, 8 and 12 and at early termination. | — |
Countries
Germany, Italy, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
BioMarin Pharmacutical Inc.
Outcome results
None listed