EXPEDITION3

(2018)

Objective

Solanezumab – To assess whether solanezumab slows cognitive decline in patients with mild Alzheimer's disease and biomarker-confirmed amyloid pathology.

Study Summary

• Solanezumab did not significantly slow cognitive decline compared to placebo.
• The primary outcome (ADAS-cog14) was not met.
• No meaningful differences in secondary cognitive or functional outcomes.
• Low incidence of ARIA and other serious adverse events.

Intervention

Phase 3, randomized, double-blind, placebo-controlled trial. Patients with mild Alzheimer’s disease received 400 mg of intravenous solanezumab or placebo every 4 weeks for 76 weeks. Participants had confirmed amyloid positivity via PET or CSF. Primary outcome: change in ADAS-cog14 from baseline to 80 weeks. Secondary measures included MMSE, ADCS-ADL, ADCS-iADL, FAQ, CDR-SB, and iADRS.

Inclusion Criteria

Ages 55–90 with mild Alzheimer's disease (MMSE 20–26) and biomarker-confirmed amyloid pathology (PET or CSF). Stable use of acetylcholinesterase inhibitors and/or memantine permitted.

Study Design

Arms: Solanezumab vs. Placebo

Patients per Arm: Solanezumab: 1057; Placebo: 1072

Outcome

• ADAS-cog14: 6.65 (Solanezumab) vs. 7.44 (Placebo); difference –0.80 (95% CI, –1.73 to 0.14; P=0.10)
• MMSE: –3.17 vs. –3.66
• ADCS-iADL: –6.17 vs. –7.17
• ADCS-ADL: –7.42 vs. –8.77
• FAQ: 5.17 vs. 5.57
• CDR-SB: 1.87 vs. 2.21
• iADRS: –12.92 vs. –14.59
• Serious AEs: 16.6% (Solanezumab) vs. 18.9% (Placebo)
• Deaths: 9 (0.9%) vs. 17 (1.6%)
• ARIA-E: 1 case in Solanezumab group; 2 in placebo; all asymptomatic

Trial not found