A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)
Summary
The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease. Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab. Trial participants who were dosed with donanemab in the main study will be enrolled to a 3-year follow up addendum. No study drug will be administered during this follow up.
Timeline
- Start
- 2020-06-19
- Primary completion
- 2023-04-14
- Completion
- 2028-11
Outcome
Met primary endpoint
registry analysis (superiority test); Donanemab vs Placebo; p <0.001; LS Mean change difference (Final Values) 2.92 (95% CI 1.508 to 4.331); Mixed Models Analysis NCT04437511 ↗
registry analysis (superiority test); Donanemab vs Placebo; p <0.001; LS Mean change difference (Final Values) 3.25 (95% CI 1.883 to 4.618); Mixed Models Analysis NCT04437511 ↗
paper donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population. PMID 37459141 ↗
release “positive results of the TRAILBLAZER-ALZ 2 Phase 3 study showing that donanemab significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer's disease.” lilly.com ↗
Publications
- Raket LL, Lu M, Evans CD, Zimmer JA, Sparks J, Collins EC, Shcherbinin S, Wang H, Nery ESM, Epelbaum S, Dell'Agnello G, Brooks DA, Sims JR, Mintun MA. Donanemab treatment effect by baseline tau burden and disease severity: Observations from the TRAILBLAZER-ALZ 2 trial. Alzheimers Dement. 2026 Jun;22(6):e71577. doi: 10.1002/alz.71577.
- Atri A, Apostolova LG, Iwata A, Wessels AM, Atkins A, Lu M, Ye W, Ryan S, Doty EG. Clinical Meaningfulness of Donanemab in Early Symptomatic Alzheimer Disease: Data From the Randomized Phase 3 TRAILBLAZER-ALZ 2 Trial. Neurol Clin Pract. 2026 Jun;16(3):e200621. doi: 10.1212/CPJ.0000000000200621. Epub 2026 May 13.
- Ardayfio P, Mullins GR, Khanna R, Zimmer JA, Wang H, Nery ESM, Evans CD, Piela P, Battioui C, Lauzon S, Anglin G, Ng HW, Jayaraman AR, Agada N, Natalie CR, Brooks DA, Sims JR. Infusion-related reactions in donanemab-treated participants with early symptomatic Alzheimer's disease. Alzheimers Dement (N Y). 2026 Mar 8;12(1):e70229. doi: 10.1002/trc2.70229. eCollection 2026 Jan-Mar.
- Zimmer JA, Sims JR, Evans CD, Nery ESM, Wang H, Wessels AM, Tronchin G, Sato S, Raket LL, Andersen SW, Sapin C, Paget MA, Gueorguieva I, Ardayfio P, Khanna R, Brooks DA, Matthews BR, Mintun MA; Alzheimer's Disease Neuroimaging Initiative. Donanemab in early symptomatic Alzheimer's disease: results from the TRAILBLAZER-ALZ 2 long-term extension. J Prev Alzheimers Dis. 2026 Feb;13(2):100446. doi: 10.1016/j.tjpad.2025.100446. Epub 2025 Dec 1.
- Lu M, Kim MJ, Collins EC, Shcherbinin S, Ellinwood AK, Yokoi Y, Brooks DA, Hansson O, Knopman DS, Sims JR, Mintun MA. Posttreatment Amyloid Levels and Clinical Outcomes Following Donanemab for Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA Neurol. 2025 Dec 1;82(12):1251-1256. doi: 10.1001/jamaneurol.2025.3869.
- Gueorguieva I, Chow K, Chua L, Shcherbinin S, Zimmer JA, Evans CD, Wang H, Nery ESM, Brooks DA, Sims JR. Donanemab exposure-response in early symptomatic Alzheimer's disease. Alzheimers Dement. 2025 Jul;21(7):e70491. doi: 10.1002/alz.70491.
- 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.
- Zimmer JA, Ardayfio P, Wang H, Khanna R, Evans CD, Lu M, Sparks J, Andersen S, Lauzon S, Nery ESM, Battioui C, Engle SE, Biffi A, Svaldi D, Salloway S, Greenberg SM, Sperling RA, Mintun M, Brooks DA, Sims JR. Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials. JAMA Neurol. 2025 May 1;82(5):461-469. doi: 10.1001/jamaneurol.2025.0065.
- Boustani M, Doty EG, Garrison LP Jr, Smolen LJ, Klein TM, Murphy DR, Spargo AW, Belger M, Johnston JA. Estimating the Economically Justifiable Price of Limited-Duration Treatment with Donanemab for Early Symptomatic Alzheimer's Disease in the United States. Neurol Ther. 2024 Dec;13(6):1641-1659. doi: 10.1007/s40120-024-00649-y. Epub 2024 Sep 18.
- Sato S, Hatakeyama N, Fujikoshi S, Katayama S, Katagiri H, Sims JR. Donanemab in Japanese Patients with Early Alzheimer's Disease: Subpopulation Analysis of the TRAILBLAZER-ALZ 2 Randomized Trial. Neurol Ther. 2024 Jun;13(3):677-695. doi: 10.1007/s40120-024-00604-x. Epub 2024 Apr 6.
- Klein EG, Schroeder K, Wessels AM, Phipps A, Japha M, Schilling T, Zimmer JA. How donanemab data address the coverage with evidence development questions. Alzheimers Dement. 2024 Apr;20(4):3127-3140. doi: 10.1002/alz.13700. Epub 2024 Feb 7.
- Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, Collins EC, Solomon P, Salloway S, Apostolova LG, Hansson O, Ritchie C, Brooks DA, Mintun M, Skovronsky DM; TRAILBLAZER-ALZ 2 Investigators. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023 Aug 8;330(6):512-527. doi: 10.1001/jama.2023.13239.
- Brodtmann A, Darby D, Oboudiyat C, Mahoney CJ, Le Heron C, Panegyres PK, Brew B. Assessing preparedness for Alzheimer disease-modifying therapies in Australasian health care systems. Med J Aust. 2023 Apr 3;218(6):247-249. doi: 10.5694/mja2.51880. Epub 2023 Mar 19. No abstract available.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Donanemab | Monoclonal antibody | 1400 mg | Intravenous |