Mclena‐1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients with Mild Cognitive Impairment Due to Alzheimer’s Disease; Interim progress

Abstract

AbstractBackgroundAccumulating evidence indicates that inflammation mediated by tumor necrosis factor alpha (TNF alpha), interleukins (e.g. IL‐1 beta, IL‐2, and IL‐6), and chemokines (e.g. IL‐8), is prominent in Alzheimer’s disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Thus, we propose that modulating systemic inflammation via a pleiotropic immunomodulator is a putative therapeutic intervention if administered at a proper time window during the course of the disease.MethodThis is a Phase II, proof‐of mechanism, placebo‐controlled clinical study on amnestic mild cognitive impairment (aMCI) male and female subjects administered 10 mg/day the immunomodulator, anti‐cancer agent lenalidomide for 12 months on a 1:1 ratio (15 placebo + 15 drug‐treated subjects total) followed by a 6 months washout period. Amyloid loads is measured by FBP PET. The primary endpoints are cognition measured via a large battery cognitive tests every 3 months, and comparison of brain amyloid loads (Florbetapir PET imaging) and neurodegeneration (volumetric MRI) pre‐ and post‐drug treatment. The secondary endpoints are safety, which is evaluated through reported adverse events (AEs), clinical laboratory tests (hematology, serum chemistry, and urinalysis), vital signs, physical and neurological examinations, and electrocardiograms. The tertiary and exploratory objectives will assess blood inflammatory markers after lenalidomide vs. placebo administration.ResultsTo date, 15 participants have signed consent, 7 screen failed, 2 withdrew consent and 6 have completed treatment after 12 months. Adverse events occurred as expected in cancer cohorts. No severe AEs have occurred so far. Importantly, assuming a 1:1 randomization in the blinded phase, several participants have received lenalidomide continuously for 12 months without interruption. Though blinded, the completers appeared to be stable.ConclusionIn the current project we aim to investigate lenalidomide as a possible AD therapy. Our study should allow determining whether or not lenalidomide is safe in subjects suffering neurological disorders, and whether it can alter the clinical course of AD. To date, AEs are as expected and the safety and tolerability are manageable. A second trial coined MCLENA 2 will start soon. It will focus on biomarker endpoints (rather than cognition) following treatment for 6 months