Design of a Phase 2, Randomized, Double‐Blind, Placebo‐Controlled, Parallel‐Group Study to Assess the Efficacy, Safety, and Tolerability of BIIB080 in Subjects with Mild Cognitive Impairment Due to Alzheimer’s Disease or Mild Alzheimer’s Disease Dementia

Abstract

AbstractBackgroundBIIB080 (formerly IONIS MAPT‐RX) is an antisense oligonucleotide (ASO) designed to bind to MAPT pre‐mRNA, promote its degradation, and prevent translation of all forms of tau protein. BIIB080 is, to our knowledge, the first tau targeting ASO to enter human clinical trials in Alzheimer’s disease (AD).BIIB080 was evaluated in Study ISIS 814907‐CS1 (NCT03186989) a Phase 1b, placebo‐controlled, double blind, multiple ascending dose clinical trial with 13‐week treatment period and 23‐week follow‐up period followed by an open‐label long term extension in patients with mild Alzheimer’s disease. BIIB080 was generally well tolerated. Importantly, robust, time‐dependent and dose‐dependent decreases in CSF total and phosphorylated tau were observed. Additionally, BIIB080 impacted aggregated tau pathology as measured by tau PET as early as 25 weeks.Based on the Phase 1b results, Biogen is conducting a Phase 2 study, Study 247AD201 (NCT05399888) that will evaluate the efficacy, safety, and tolerability of BIIB080 in participants with mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s disease dementia.MethodRandomized, double‐blind, placebo‐controlled, parallel‐group Phase 2 study (CELIA), is enrolling approximately 735 individuals aged 50‐80 years, with MCI due to Alzheimer’s disease or mild Alzheimer’s disease dementia, Clinical Dementia Rating (CDR) global score 0.5‐1, Mini Mental State Examination (MMSE) score 22‐30, objective evidence of cognitive impairment at Screening, and evidence of amyloid pathology as measured by PET or cerebrospinal fluid (CSF) sampling.The Phase 2 study will randomize participants to receive 1 of 3 different dose regimens of intrathecal (IT) BIIB080 or placebo every 12 or 24 weeks during the 76‐week placebo‐controlled period. The primary endpoint will assess the dose‐response in change from Baseline to Week 76 on the CDR‐SB.The study includes a tau PET substudy to assess the effect of BIIB080 on tau aggregates with 18F‐MK6240.ResultThe Ph2 CELIA study is currently recruiting participants.ConclusionThe ongoing Ph2 CELIA trial will assess the efficacy, safety and tolerability of BIIB080, compared to placebo in subjects with MCI due to Alzheimer’s disease or mild Alzheimer’s disease dementia.