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. Objective To assess the long-term safety and tolerability of SC gantenerumab at doses of up to 1200 mg every 4 weeks (Q4W) in OLE participants who previously received placebo or gantenerumab in the DB part of SR. Methods Participants of the DB part of SR, who met the eligibility criteria for the OLE, were offered the opportunity to receive gantenerumab up-titrated to 1200 mg Q4W according to prespecified titration regimens. Safety and tolerability were assessed using magnetic resonance imaging (MRI), physical and neurologic examinations, and adverse event monitoring. Results Overall, 154 participants were rolled over from the DB part of SR and received at least one dose of gantenerumab in the SR OLE. The median duration of treatment was 2.9 years (152.9 weeks). Forty-seven (30.5%) participants had an amyloid-related imaging abnormalities – edema (ARIA-E) MRI finding, and 51 (33.1%) had an ARIA – hemorrhage MRI finding. Most ARIA-E findings were asymptomatic and manageable by MRI monitoring and dose intervention. There were no unexpected safety findings. Conclusions SC gantenerumab at doses of up to 1200 mg Q4W was well tolerated with no unexpected safety findings in participants with prodromal Alzheimer's disease. Trial registration: ClinicalTrials.gov ID NCT01224106