052 SKYLINE study design efficacy and safety of gantenerumab in participants at-risk for Alzheimers disease

The anti-amyloid beta (Aβ) monoclonal antibody gantenerumab is in late-phase clinical development for early (prodromal-to-mild) Alzheimer’s disease (AD). SKYLINE is an upcoming Phase III multicentre, ran- domised, parallel-group, double-blind, placebo-controlled secondary prevention study, evaluating the efficacy and safety of subcutaneous gantenerumab in participants at risk for, or in the earliest stages of, AD.

SKYLINE will enrol ~1,200 cognitively unimpaired participants, aged 60–80, with confirmed Aβ pathology (cerebrospinal fluid or positron emission tomography).

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 randomisation.

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; pharmacodynamic biomarkers; pharmacokinetics; and identification of additional biomarkers.

SKYLINE will be the first secondary prevention study of subcutaneous gantenerumab in cognitively unim- paired participants at risk for, or in the earliest stages of, AD.