BACKGROUND: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an 
enzyme-replacement therapy that has been developed to treat neuronal ceroid 
lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes 
progressive dementia in children.
METHODS: In a multicenter, open-label study, we evaluated the effect of 
intraventricular infusion of cerliponase alfa every 2 weeks in children with 
CLN2 disease who were between the ages of 3 and 16 years. Treatment was 
initiated at a dose of 30 mg, 100 mg, or 300 mg; all the patients then received 
the 300-mg dose for at least 96 weeks. The primary outcome was the time until a 
2-point decline in the score on the motor and language domains of the CLN2 
Clinical Rating Scale (which ranges from 0 to 6, with 0 representing no function 
and 3 representing normal function in each of the two domains), which was 
compared with the time until a 2-point decline in 42 historical controls. We 
also compared the rate of decline in the motor-language score between the two 
groups, using data from baseline to the last assessment with a score of more 
than 0, divided by the length of follow-up (in units of 48 weeks).
RESULTS: Twenty-four patients were enrolled, 23 of whom constituted the efficacy 
population. The median time until a 2-point decline in the motor-language score 
was not reached for treated patients and was 345 days for historical controls. 
The mean (±SD) unadjusted rate of decline in the motor-language score per 
48-week period was 0.27±0.35 points in treated patients and 2.12±0.98 points in 
42 historical controls (mean difference, 1.85; P<0.001). Common adverse events 
included convulsions, pyrexia, vomiting, hypersensitivity reactions, and failure 
of the intraventricular device. In 2 patients, infections developed in the 
intraventricular device that was used to administer the infusion, which required 
antibiotic treatment and device replacement.
CONCLUSIONS: Intraventricular infusion of cerliponase alfa in patients with CLN2 
disease resulted in less decline in motor and language function than that in 
historical controls. Serious adverse events included failure of the 
intraventricular device and device-related infections. (Funded by BioMarin 
Pharmaceutical and others; CLN2 ClinicalTrials.gov numbers, NCT01907087 and 
NCT02485899 .).