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SKYLINE STUDY DESIGN: EFFICACY AND SAFETY OF GANTENERUMAB IN PARTICIPANTS AT-RISK FOR OR AT THE EARLIEST STAGES OF ALZHEIMER’S DISEASE
Abstract
Aims
The anti-amyloid beta (Aβ) monoclonal antibody gantenerumab is in late-phase clinical development for early (prodromal-to-mild) Alzheimer’s disease (AD). Here we describe an upcoming Phase III multicentre, randomised, parallel-group, double-blind, placebo-controlled secondary prevention study (SKYLINE), evaluating the efficacy and safety of subcutaneous gantenerumab in participants at risk for or at the earliest stages of AD.
Methods
SKYLINE will enrol ~1,200 cognitively unimpaired participants (Clinical Dementia Rating Global Score=0 and Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index ≥80), aged 60–80, with confirmed Aβ pathology (cerebrospinal fluid [CSF] or positron emission tomography [PET]). Screening includes an optional exploratory blood-based biomarker (BBBM) pre-screening to predict Aβ positivity. Participants will be randomised 1:1 to 211 weeks subcutaneous gantenerumab (titrated to 1,020 mg monthly dosage) or placebo treatment administered weekly or every other week. Any participant confirmed as progressing to mild cognitive impairment or AD dementia during the study will undergo a blinded post-progression dose escalation, during which participants on placebo switch to gantenerumab. All parties will remain blinded to the assigned treatment at randomization.
Results
The primary endpoint is change from baseline to Year 4 in the Preclinical Alzheimer’s Cognitive Composite-5 score. Secondary and exploratory objectives include further efficacy assessments (e.g., clinical progression), safety (e.g., adverse events, amyloid-related imaging abnormalities), pharmacodynamic biomarkers (Aβ/Tau PET, CSF, BBBM), pharmacokinetics, and identification of additional biomarkers.
Conclusions
SKYLINE will be the first secondary prevention study of subcutaneous gantenerumab in cognitively unimpaired participants at risk for or at the earliest stages of AD.