DESIGN AND EXECUTION OF THE NILVAD STUDY

Abstract

NILVAD is an investigator driven phase III clinical trial of nilvadipine in mild to moderate Alzheimer's disease. Nilvadipine, a dihyropyridine calcium channel blocker, is a licensed antihypertensive and is being repurposed for AD based on clinical and basic science evidence for its potential as a disease-modifying agent in AD. 511 subjects with mild to moderate AD were recruited across 23 sites in 9 different European countries. Subjects received 8 mg over encapsulated nilvadipine or matching placebo over a period of 18 months. The sponsor of the trial was St. James's Hospital, Dublin. Academic trial units were used to monitor the trial in each country. The primary outcome measures were Alzheimer's disease Assessment Scale Cognitive (ADAS-Cog) and Clinical Dementia Rating Scale sum of boxes (CDR-sb). There were a number of challenges to overcome in successfully completing this trial including: recruitment and exclusion of patients on multiple antihypertensive agents, in particular other calcium channel blockers and beta blockers; IMP manufacture: sourcing and over capsulation of study drug and matching placebo and independently establishing blindedness and stability testing of the over encapsulated repurposed agent; safety monitoring and pharmacovigilance. NILVAD is an example of an investigator driven repurposing program for an antihypertensive in AD. The NILVAD trial provides multiple learnings that can be captured and help inform future efforts in this challenging area of drug discovery.