Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
Summary
This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 116. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.
Timeline
- Start
- 2018-08-22
- Primary completion
- 2022-09-23
- Completion
- 2022-11-28
Outcome
Missed primary endpoint
Stopped: “Decision to terminate development of Gantenerumab for treatment of prodromal/mild/early stage Alzheimer's disease following results of a pre-planned analysis of the safety and efficacy of Gant in Graduate I\&II (WN29922/WN39658).”
registry analysis (superiority test); Placebo: DBT vs Gantenerumab: DBT; p = 0.2998; Difference in Adjusted mean -0.19 (95% CI -0.55 to 0.17); ANCOVA NCT03443973 ↗
paper Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. PMID 37966285 ↗
Publications
- Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.
- Asada T, Thanasopoulou A, Delmar P, Wojtowicz J, Smith J, Yoshiyama Y, Yokoi K, Watanabe C, Isozaki M, Ozaki R, Ishida T, Tatsuda H, Tamaoka A. Japanese participant data from three gantenerumab trials in early Alzheimer's disease. Alzheimers Dement. 2025 Apr;21(4):e70192. doi: 10.1002/alz.70192.
- Bittner T, Tonietto M, Klein G, Belusov A, Illiano V, Voyle N, Delmar P, Scelsi MA, Gobbi S, Silvestri E, Barakovic M, Napolitano A, Galli C, Abaei M, Blennow K, Barkhof F. Biomarker treatment effects in two phase 3 trials of gantenerumab. Alzheimers Dement. 2025 Feb;21(2):e14414. doi: 10.1002/alz.14414. Epub 2025 Jan 30.
- Salloway S, Wojtowicz J, Voyle N, Lane CA, Klein G, Lyons M, Rossomanno S, Mazzo F, Bullain S, Barkhof F, Bittner T, Schneider A, Grundman M, Aldea R, Boada M, Smith J, Doody R. Amyloid-Related Imaging Abnormalities (ARIA) in Clinical Trials of Gantenerumab in Early Alzheimer Disease. JAMA Neurol. 2025 Jan 1;82(1):19-29. doi: 10.1001/jamaneurol.2024.3937.
- Bateman RJ, Smith J, Donohue MC, Delmar P, Abbas R, Salloway S, Wojtowicz J, Blennow K, Bittner T, Black SE, Klein G, Boada M, Grimmer T, Tamaoka A, Perry RJ, Turner RS, Watson D, Woodward M, Thanasopoulou A, Lane C, Baudler M, Fox NC, Cummings JL, Fontoura P, Doody RS; GRADUATE I and II Investigators and the Gantenerumab Study Group. Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease. N Engl J Med. 2023 Nov 16;389(20):1862-1876. doi: 10.1056/NEJMoa2304430.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Gantenerumab | Monoclonal antibody | — | Subcutaneous |