Table 2 Ongoing trials of gantenerumab
Study name, design, and NCT | Study population | Dose | Objective and primary endpoint | Key secondary endpoints | Estimated completion date |
|---|---|---|---|---|---|
GRADUATE I and II Parallel, global, multicenter, double-blind, placebo-controlled, randomized phase 3 studies (study start date: 2018) (NCT03444870) (NCT03443973) | N = 985 (GRADUATE I) N = 981 (GRADUATE II) Early (prodromal to mild) ADa, 50–90 years, evidence of the AD pathological process confirmed by CSF tau/Aβ42 or amyloid PET scan, abnormal memory function, MMSE score ≥ 22, CDR-GS = 0.5 or 1, any APOE ε4 allele status | Gantenerumab 9-month universal dose-titration regardless of APOE ε4 allele status to 510 mg SC every 2 weeks (Fig. 3) Placebo | Objective: to evaluate the efficacy and safety of subcutaneous gantenerumab vs placebo in patients with early AD (i.e., MCI-AD to mild AD) Primary endpoint: change from baseline to week 116 in CDR-SB vs placebo | MMSE, ADAS-Cog 13, Verbal Fluency, Coding, FAQ, ADCS-ADL, safety CSF biomarkers, amyloid and tau PET, MRI, plasma biomarkers | Q4 2022 |
Open ROAD A long-term, open-label rollover safety and tolerability study of gantenerumab (study start date: 2020) (NCT04339413) | N = 116 Participants who completed Scarlet RoAD OLE (NCT01224106) or Marguerite RoAD OLE (NCT02051608) | Gantenerumab 1200 mg SC Q4W with universal titration (Fig. 3) | Objective: to define the long-term safety and tolerability of gantenerumab in patients with AD Primary endpoint: AEs, treatment discontinuation, ISR, ARIA-E, ARIA-H, ADAs | May 2025 | |
GRADUATION Multicenter, phase 2, open-label, single-arm, pharmacodynamic study (study start date: 2020) (NCT04592341) | N = 192 Probable mild dementiaa, 50–90 years, AD pathology confirmed by amyloid PET scan | Gantenerumab 255 mg SC Q1W with an option for administration by study partner or non-professional) caregivers (Fig. 3) Placebo | Objective: to evaluate the effect of a once-weekly gantenerumab dosing regimen on the change in deposited amyloid Primary endpoint: change from baseline in deposited amyloid as measured by brain amyloid PET centiloid levels | Responses to home administration questionnaire (the home administration questionnaire will capture confidence, ease of use, convenience, and overall satisfaction) Safety | November 2023 |
DIAN-TU-001 OLE (study start date: 2020) (NCT01760005) | Patients who complete DIAN-TU-001 (NCT01760005) | Gantenerumab SC uptitrated to 1500 mg Q2W Individuals in the solanezumab arm of the DIAN-TU-001 may switch to gantenerumab | Objective: to assess the effects of early and larger magnitude reduction of amyloid plaques on downstream AD processes, the clinical benefits associated with the continued removal of amyloid plaques in DIAD mutation carriers across asymptomatic and symptomatic stages of AD, and the validity of strategies to slow clinical onset of AD and its progression using gantenerumab Primary endpoint: change from baseline in: each component of DIAN-MCE; CDR-SB; Functional Assessment Scale; PiB-PET Aβ; CSF total Aβ; CSF t-tau; p-tau181 CSF NfL; precuneus thickness and hippocampal volume Safety | 2023 | |
POSTGRADUATE Open-label, multicenter, phase 3 rollover study (study start date: 2021) (NCT04374253) | Planned N = 2032 Participants who completed either GRADUATE I (NCT03444870) or II (NCT03443973) double-blind part or OLE trial | Gantenerumab 9-month universal dose-titration regardless of APOE ε4 allele status to 510 mg SC every 2 weeks (see Fig. 3) | Objective: to define the long-term safety and tolerability of gantenerumab in patients with AD Primary endpoint: AEs, SAEs, C-SSRS Score, ARIA-E, ARIA-H, ISRs | CDR, MMSE, ADAS-Cog13, Verbal fluency, Coding, FAQ, ADCS-ADL | December 2024 |
PCEx Non-interventional, patient- and caregiver-centered qualitative study (study start date: 2021) | Planned N = 100 pairs of patients and their caregivers from the GRADUATE I, GRADUATE II, and POSTGRADUATE studies | Non-interventional | Objective: to evaluate the treatment burden associated with gantenerumab for patients and their care partners to optimize the gantenerumab treatment experience in the real world Primary endpoint: survey responses of patients’ and caregivers’ experiences with gantenerumab SC administration | October 2022 | |
SKYLINE Phase 3, randomized, double-blind, placebo-controlled secondary prevention trial (estimated study start date: 2022) (NCT05256134) | Planned N = 1200 Cognitively unimpaired, 60–80 years, evidence of cerebral amyloid accumulation, CSF p-Tau181/Aβ42 ratio > 0.04 or amyloid PET visual read positive; screening includes an optional exploratory BBBM prescreening to predict Aβ positivity | Participant-centric flexible dosing Target gantenerumab dose 1200 mg SC Q1W or Q2W (Fig. 3) | Objective: to evaluate the efficacy and safety of gantenerumab in amyloid-positive, cognitively unimpaired patients who are amyloid positive and at risk for AD Primary endpoint: PACC-5 Composite endpoint to assess cognition in asymptomatic AD; logical memory from the WMS; FCSRT; coding from the WAIS-IV; MMSE; Category fluency test | CFIa, A-IADL-Q-SV, CDR-SB Safety: MRI, AEs, C-SSRS, ADAs BBBM, vMRI, amyloid and tau PET, CSF biomarkers, pharmacokinetics | October 2028 |