Developing Topics.

Background: Amyloid-plaque removal by monoclonal antibody therapies slows progression in symptomatic Alzheimer's disease (AD), but effects on preventing the onset of symptoms and dementia in asymptomatic people with amyloid plaques are unknown. We report the final primary and secondary outcomes of the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial to evaluate amyloid-plaque removal in delaying disease progression, including symptom onset, in symptomatic and asymptomatic dominantly inherited Alzheimer's disease (DIAD) individuals treated for up to a decade.

Method: This double-blind, phase 2/3 trial (2012-2019), followed by open-label extension (OLE), investigated varying gantenerumab doses up to 1500 mg subcutaneous q2 weeks [NCT01760005].

Developing Topics.

Background: Anti-amyloid monoclonal antibody therapies have successfully removed amyloid plaque as measured using imaging techniques. However, the characteristic fluid biomarker trajectories following plaque removal remains understudied, particularly during the preclinical phases of disease. We investigated biomarker trajectories in the context of the gantenerumab open label extension (OLE) of the Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) secondary prevention trial (DIAN-TU-001) in Autosomal Dominant Alzheimer's disease (ADAD) mutation carriers.

Developing Topics.

Background: Anti-amyloid monoclonal antibody therapies for AD have documented plaque removal on amyloid PET scans. We evaluate the findings for amyloid PET, tau PET, FDG PET and volumetric MRI over the course the open label extension (OLE) for the DIAN-TU gantenerumab treatment, compared to the last imaging obtained prior to the OLE (to evaluate for potential rebound effects) and in comparison to longitudinal imaging in the DIAN Observational study.

Method: This double-blind, phase 2/3 trial (2012-2019), followed by open-label extension (OLE), investigated varying gantenerumab doses up to 1500 mg SQ q2 weeks [NCT NCT01760005].

Long-term safety of gantenerumab in participants with Alzheimer's disease: A phase III, open-label extension study (SCarlet RoAD).

Background: Gantenerumab is a fully human anti-amyloid-β (Aβ) immunoglobulin G1 monoclonal antibody for subcutaneous (SC) administration. The efficacy and safety of low-dose (105 mg or 225 mg) gantenerumab were investigated in SCarlet RoAD (SR; NCT01224106), a Phase III, double-blind (DB), placebo-controlled study in participants with prodromal Alzheimer's disease. Following a pre-planned futility analysis, SR was converted into an open-label extension (OLE) study.

Amyloid-Related Imaging Abnormalities in Clinical Trials of Gantenerumab in Early Alzheimer Disease.

Importance: Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae.

Objectives: To describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E).

Design, Setting, And Participants: Secondary data collection from the GRADUATE I/II phase 3 randomized, double-blind, placebo-controlled, 116-week parallel-group studies and their open-label extensions, including PostGraduate, with up to 210 (mean, 125) weeks of total gantenerumab treatment were conducted between 2018 and 2023.