drugset / Trial / NCT02008357
Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss
Phase 3
Completed
1169 enrolled
Eli Lilly and Company
Alzheimer's Therapeutic Research Institute · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The purpose of this study is to test whether an investigational drug called solanezumab can slow the progression of memory problems associated with brain amyloid (protein that forms plaques in the brains of people with Alzheimer Disease \[AD\]).
Timeline
- Start
- 2014-02-28
- Primary completion
- 2022-12-27
- Completion
- 2023-06-08
Outcome
Missed primary endpoint
registry analysis (superiority test); Solanezumab vs Placebo; p = 0.260; LS Mean difference (Final Values) -0.30 (95% CI -0.816 to 0.220); Natural Cubic Spline (NCS) method NCT02008357 ↗
paper Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks PMID 37458272 ↗
release “Results of the A4 Study clearly showed that the primary and secondary endpoints were not met.” lilly.com ↗
Publications
- Stites SD, Schumann R, Shi Y, Mechanic-Hamilton D, Wolk DA; Alzheimer's Disease Neuroimaging Initiative. Depression and anxiety modify cognitive concerns associated with amyloid and early clinical impairment. Neuropsychology. 2026 Jun 15:10.1037/neu0001086. doi: 10.1037/neu0001086. Online ahead of print.
- Digma LA, Young CB, Winer JR, Cody KA, Younes K, Sheng J, Insel PS, Rissman RA, Sperling R, Mormino EC. Continuum of Core 1 biomarkers in preclinical Alzheimer's disease. Alzheimers Res Ther. 2026 Apr 10;18(1):133. doi: 10.1186/s13195-026-02044-1.
- Beyrer J, Sheff Z, Payakachat N, Chandler JM, Chen YF, Kubisiak J, Lee A, Holdridge KC, Yaari R, Aisen P, Rafii MS, Sperling RA; A4 and LEARN Study Teams. Increase in healthcare utilization and Medicare payment with progression of preclinical Alzheimer's disease. J Prev Alzheimers Dis. 2026 Jun;13(6):100547. doi: 10.1016/j.tjpad.2026.100547. Epub 2026 Apr 1.
- Hibar DP, Bauer A, Rabe C, Borlinghaus N, Jethwa A, Kollmorgen G, Di Domenico A, Zetterberg H, Blennow K, Masters CL, Sperling RA, Bittner T. Elecsys pTau217 plasma immunoassay detection of amyloid pathology in clinical cohorts. Alzheimers Dement. 2026 Jan;22(1):e71009. doi: 10.1002/alz.71009.
- Shirzadi Z, Schultz AP, Loghmani N, Yang HS, Ford J, Yaari R, Properzi M, Yau WW, Liu L, Rafii MS, Donohue MC, Brickman AM, Jack CR Jr, Greenberg SM, Aisen P, Sperling RA, Chhatwal JP; A4 Study Team. Independent effects of white matter lesion volume and APOE varepsilon4 on ARIA-H in A4 Study. Alzheimers Dement. 2025 Oct;21(10):e70751. doi: 10.1002/alz.70751.
- Digma LA, Young CB, Winer JR, Cody KA, Younes K, Sheng J, Insel PS, Rissman RA, Sperling R, Mormino EC. Continuum of Core 1 Biomarkers in Preclinical Alzheimer's Disease. medRxiv [Preprint]. 2025 Sep 19:2025.09.17.25336007. doi: 10.1101/2025.09.17.25336007.
- Devanarayan V, Donohue MC, Sperling RA, Johnson KA, Ye Y, Charil A, Doherty T, Tian L, Raman R, Aisen PS, Kramer LD, Irizarry MC, Dhadda S. Multimodal prognostic modeling of individual cognitive trajectories to enhance trial efficiency in preclinical Alzheimer's disease. Alzheimers Dement. 2025 Sep;21(9):e70702. doi: 10.1002/alz.70702.
- Farina FR, Bennett M, Grill JD, Sperling R, Lawlor B, Griffith JW. Association of Alzheimer's disease concerns with amyloid burden and lifestyle behaviors in cognitively unimpaired older adults. Alzheimers Dement. 2025 Jun;21(6):e70225. doi: 10.1002/alz.70225.
- Dubbelman MA, Liu A, Donohue MC, Langford O, Raman R, Rentz DM, Amariglio R, Sperling RA, Aisen PS, Marshall GA; as the A4 Study team. Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. 2025 Jun 24;104(12):e213775. doi: 10.1212/WNL.0000000000213775. Epub 2025 May 29.
- Sperling RA, Donohue MC, Raman R, Rafii MS, Johnson K, Masters CL, van Dyck CH, Iwatsubo T, Marshall GA, Yaari R, Mancini M, Holdridge KC, Case M, Sims JR, Aisen PS; A4 Study Team. Trial of Solanezumab in Preclinical Alzheimer's Disease. N Engl J Med. 2023 Sep 21;389(12):1096-1107. doi: 10.1056/NEJMoa2305032. Epub 2023 Jul 17.
- Lewis CK, Bernstein OM, Grill JD, Gillen DL, Sultzer DL. Anxiety and Depressive Symptoms and Cortical Amyloid-beta Burden in Cognitively Unimpaired Older Adults. J Prev Alzheimers Dis. 2022;9(2):286-296. doi: 10.14283/jpad.2022.13.
- Grober E, Lipton RB, Sperling RA, Papp KV, Johnson KA, Rentz DM, Veroff AE, Aisen PS, Ezzati A. Associations of Stages of Objective Memory Impairment With Amyloid PET and Structural MRI: The A4 Study. Neurology. 2022 Mar 29;98(13):e1327-e1336. doi: 10.1212/WNL.0000000000200046. Epub 2022 Feb 23.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Solanezumab | Protein / enzyme biologic | 1600 mg | Intravenous |