A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo in Participants With Prodromal to Mild Alzheimer's Disease (AD).

Summary

This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of crenezumab versus placebo in participants with prodromal to mild AD. Participants will be randomized 1:1 to receive either intravenous (IV) infusion of crenezumab or placebo every 4 weeks (Q4W) for 100 weeks. The final efficacy and safety assessment will be performed 52 weeks after the last crenezumab dose. Participants will then have the option to enter the Open Label Extension (OLE) study if eligible. Participants who do not enter the OLE study will have additional follow-up visits at 16 and 52 weeks after the last dose, primarily for safety and also for limited efficacy assessments.

Timeline

Start

2016-03-22

Primary completion

2019-05-31

Completion

2019-05-31

Outcome

Missed primary endpoint

Stopped: “This study was discontinued due to an interim analysis in this study, which indicated that Crenezumab was unlikely to meet its primary endpoint.”

registry analysis (superiority test); Placebo vs Crenezumab; Least Squares Mean Difference -0.17 (95% CI -0.86 to 0.53) NCT02670083 ↗

paper The between-group difference in mean change from baseline in CDR-SB score (placebo minus crenezumab) was -0.17 (95% CI, -0.86 to 0.53; P = .63) at week 105 PMID 36121669 ↗

Publications

• 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.
• 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.
• Teng E, Manser PT, Shah M, Pickthorn K, Hu N, Djakovic S, Swendsen H, Blendstrup M, Faccin G, Ostrowitzki S, Sink KM. The Use of Episodic Memory Tests for Screening in Clinical Trials for Early Alzheimer's Disease: A Comparison of the Free and Cued Selective Reminding Test (FCSRT) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). J Prev Alzheimers Dis. 2023;10(1):41-49. doi: 10.14283/jpad.2022.101.
• Ostrowitzki S, Bittner T, Sink KM, Mackey H, Rabe C, Honig LS, Cassetta E, Woodward M, Boada M, van Dyck CH, Grimmer T, Selkoe DJ, Schneider A, Blondeau K, Hu N, Quartino A, Clayton D, Dolton M, Dang Y, Ostaszewski B, Sanabria-Bohorquez SM, Rabbia M, Toth B, Eichenlaub U, Smith J, Honigberg LA, Doody RS. Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials. JAMA Neurol. 2022 Nov 1;79(11):1113-1121. doi: 10.1001/jamaneurol.2022.2909.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Crenezumab	Monoclonal antibody	60 mg/kg	Intravenous

Indications