Abstract Details

Gantenerumab, a fully human anti-amyloid beta (Aβ) monoclonal antibody in development for Alzheimer’s disease (AD), binds to and removes Aβ species. Two ongoing multicenter, randomized, double-blind, placebo-controlled, Phase III studies, GRADUATE I and II, assess the efficacy and safety of subcutaneous gantenerumab (1,020 mg monthly dosage) in early (prodromal-to-mild) AD.

To describe the study design of an open-label, multicenter, rollover study (PostGraduate, NCT04374253), enabling the evaluation of gantenerumab’s long-term safety, tolerability, and efficacy in participants from GRADUATE I (NCT03444870) and GRADUATE II (NCT03443973).

Participants treated with gantenerumab who completed either parent study (up to 2,032 participants) will receive subcutaneous gantenerumab (510 mg every 2 weeks [Q2W]) for 2 years. Participants naive to gantenerumab will up-titrate in 3 steps (120 mg, 225 mg, 510 mg every 4 weeks) to target 510 mg Q2W. Participants will remain blinded to previous treatment assignment. The primary objective is to evaluate safety and tolerability by assessing adverse events, physical examinations, vital signs, laboratory tests, suicidality, amyloid-related imaging abnormalities, and injection-site reactions. Secondary and exploratory objectives include evaluation of efficacy (measures of cognition, function, quality of life, and caregiver burden aligned with parent studies), pharmacokinetics, anti-drug antibodies, and longitudinal biomarkers (amyloid and tau positron emission tomography in respective substudies, fluid biomarkers, magnetic resonance imaging).

N/A

PostGraduate is a scientifically valuable study of safety, clinical measures, and fluid and imaging biomarkers in a large group of participants, enriched for amyloid positivity and short-term memory loss, and treated continuously for up to 4 years.