DIAN-TU-001: A Phase II/III Randomized, Double-Blind, Placebo-Controlled, Cognitive Endpoint, Multicenter Study of Potential Disease Modifying Therapies in Individuals at Risk for and with Dominantly Inherited Alzheimer's Disease.
Funded by Washington University School of Medicine in St. Louis (USA).
The aim of this study is to assess the safety, tolerability, biomarker and cognitive efficacy of investigational products (Gantenerumab, Solanezumab and Atabecestat [JNJ-54861911]) in subjects who are known to have an Alzheimer’s disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive impairment and improves disease-related biomarkers.
Subjects in DIAN are recruited from families that have at least one member who has been identified as having a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP), associated with autosomal dominant Alzheimer’s disease and having a very high penetrance (near 100%). The pathological processes that define Alzheimer’s disease (AD), amyloid plaques and neurofibrillary tangles, start to develop 10-20 years before clinical symptoms. The ability to identify individuals destined to develop AD provides a unique opportunity to assess the efficacy of therapies at asymptomatic and very early stages of dementia. Although there are differences between dominantly inherited AD and the more common age-associated sporadic disease, the results of the early intervention in this study will have implications for future studies and treatments in sporadic AD. The primary endpoint of this study is that the active drug group will have a slower rate of progression on the cognitive composite endpoint compared to the mutation-carrier placebo group after treatment for a minimum of 4 years. Studies in individuals who carry a mutation linked to early onset AD suggest that biomarker changes are detectable 15 or more years before the anticipated time of disease onset. Currently there are two Italian Centers involved in the DIAN-TU study: IRCCS Fatebenefratelli Saint John of God in Brescia (PI: Dr. Giovanni B Frisoni) and University of Florence (PI: Prof. Sandro Sorbi).