Meaningful Outcomes and Multi-Site Readiness for Clinical Trials in Juvenile Neuronal Ceroid Lipofuscinosis

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The neuronal ceroid lipofuscinosis (NCL) therapeutic pipeline is rapidly expanding. The NCLs are rare, devastating, neurodegenerative lysosomal storage disorders that mainly affect children. Juvenile NCL (CLN3 disease) is the most prevalent form, with a complex set of multi-domain signs and symptoms that gradually progress over 20 years and culminate in premature death. Currently, there are no approved disease-modifying therapies. This proposal will foster collaboration between international leaders in NCL research, the University of Rochester (Rochester, New York) and the University of Hamburg (Hamburg, Germany). This multi-center, multi-national partnership mirrors the future model for clinical trial implementation and lays the foundation for development of novel therapeutics for CLN3 disease. The proposal will address critical challenges for the design and implementation of clinical trials in CLN3 disease: optimizing sensitive clinical assessments that measure how patients feel and function, validating early readouts of efficacy for go-no go decision making in phase 2 trials, and preparing for rigorous and consistent disease evaluation across multiple clinical trial sites. In parallel, our aims are: 1) to refine approaches to systematic and comprehensive assessment of CLN3 disease in order to best quantify progression in future trials, 2) to validate quantitative brain neuroimaging measurements as biomarkers of disease progression for phase 2 trials, and 3) to prepare for reproducible multi-site use of clinical outcome assessment tools. During the award period, we will engage the Food and Drug Administration in clinical outcome assessment and biomarker qualification processes to ensure optimal preparation for future regulatory review processes for emerging CLN3 disease therapeutic trials.