Baseline participant characteristics of GRADUATION: a study to evaluate once‐weekly subcutaneous administration of gantenerumab

Abstract Background Gantenerumab, a human monoclonal antibody targeting aggregated beta‐amyloid (Abeta), is a potential disease‐modifying treatment for early (prodromal‐to‐mild) Alzheimer’s disease (AD). Exposure‐dependent signals of clinical efficacy were observed with low‐dose gantenerumab in post hoc analyses of the SCarlet RoAD study (NCT01224106) in participants with prodromal AD. 1 Open‐label extension studies with uptitration to doses of up to 1,200 mg every 4 weeks (q4w) confirmed substantial Abeta removal without new or unexpected safety findings. 2 Two Phase III studies are ongoing to assess efficacy and safety of subcutaneous gantenerumab in early AD, using a target dose of 510 mg q2w (GRADUATE I/GRADUATE II [NCT03444870/NCT03443973]). The GRADUATION trial (NCT04592341) will evaluate the safety, pharmacodynamics (PD), and pharmacokinetics (PK) of once‐weekly (q1w) administration of gantenerumab (255 mg) in participants with early (prodromal‐to‐mild) AD. Subcutaneous q1w administration of gantenerumab may simplify home dosing to meet the individual needs and preferences of people with AD and their caregivers, and to improve their experience by providing additional flexibility and convenience. Methods In this open‐label, single arm, Phase II study, participants will receive gantenerumab by subcutaneous injection over a 2‐year period, starting with 120 mg q4w, followed by 255 mg q4w and q2w for 12 weeks each, and a target dose of 255 mg q1w. This target dose is equivalent to the 1,020 mg/month studied in the GRADUATE trials. The primary objective is to evaluate the PD effect of a q1w dosing regimen of gantenerumab on brain amyloid load measured by positron emission tomography. Secondary objectives include assessment of gantenerumab administration by a caregiver at home, safety, and PK/PD relationships. Exploratory objectives will include additional imaging and plasma biomarkers, and cognitive and functional assessments. Results Recruitment for GRADUATION is complete. Participants were enrolled from Belgium, France, Germany, Italy, Poland, Spain, UK, and US. Detailed baseline characteristics will be presented. Conclusion The GRADUATION study will determine the effect of q1w administration of gantenerumab on brain amyloid load, safety, PK/PD and biomarker endpoints, and assess the feasibility of administration by caregivers at home. 1. Ostrowitzki S, et al. Alzheimers Res Ther 2017;9:95 2. Klein G, et al. Alzheimers Res Ther 2019;11:101