Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium and postopErative Cognitive Dysfunction

Phase 2 Completed 203 enrolled Miles Berger, MD PhD

RandomizedParallel-groupQuadruple-blindPrevention

Summary

This research study will evaluate the effectiveness and estimate the feasibility of administering an investigational drug called 'CN-105' (the study drug), to prevent postoperative cognitive decline, delirium (serious confusion) and underlying brain inflammatory and brain activity changes in adults 60 years and older undergoing surgery.

Timeline

Start: 2018-07-15
Primary completion: 2022-12-28
Completion: 2022-12-28

Outcome

Results reported · no primary-endpoint met/missed verdict (typical of a dose-finding / safety study)

registry analysis (other test); CN-105 vs Placebo; p = 0.025; Wilcoxon (Mann-Whitney) NCT03802396 ↗

Publications

Timko NJ, Cooter Wright M, Smith MR, Boykin PC, Emerson JM, Woldorff MG, Eleswarpu S, Herbert JT, Moretti EW, Devinney MJ, Ayoub CM, Rockhold FW, Ryu D, Syed A, VanDusen KW, Bunning T, Hsia BJ, Bolognesi MP, Jiranek WA, Zetterberg H, Blennow K, Huebner JL, Li Z, Reekes TH, Browndyke JN, Laskowitz DT, Berger M; MARBLE Study Investigators. Apolipoprotein E Mimetic Peptide CN-105 and Postoperative Delirium in Older Patients: The Phase 2 MARBLE Randomized Clinical Trial. JAMA Netw Open. 2026 Apr 1;9(4):e262289. doi: 10.1001/jamanetworkopen.2026.2289.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	CN-105	Peptide	0.1 mg/kg	Intravenous
Subject	CN-105	Peptide	0.5 mg/kg	Intravenous
Subject	CN-105	Peptide	1 mg/kg	Intravenous