Aims

The objective of the Phase 2 portion of the ELEVAGE study was to replicate the results of the post‐hoc type 2 diabetes (T2D) subgroup from the Phase 3 STEADFAST trial through demonstration of a beneficial effect of azeliragon on cognition.

Methods

The ELEVAGE Phase 2 portion was a randomized, double‐blind, placebo‐controlled study originally targeting 100 participants with probable mild Alzheimer’s disease (AD) (Screening MMSE 21‐ 26, CDR global 0.5‐1, ADAScog14 ≥ 10) and T2D (HbA1c 6.5%‐9.5%) receiving stable acetylcholinesterase inhibitors and/or memantine, evaluating the efficacy and safety of 6 months of treatment with azeliragon 5 mg/day relative to placebo. The primary endpoint was ADAS‐cog14 change from baseline at Month 6. Secondary endpoints included change from baseline in CDR‐sb, Functional Activities Questionnaire (FAQ), and Amsterdam Instrumental Activities of Daily Living (A‐IADL) at Month 6.

Results

Forty‐three participants were randomized (21 azeliragon, 22 placebo) at 29 sites in the US and Canada. The azeliragon treated group had a 1.8 ± 0.8 (LSmean ± SE) point decline from baseline in ADAS‐cog14 compared to a placebo decline of 0.35 ± 0.69. The treatment difference (1.45 points) was not statistically significant (p=0.17). Consistent with previous studies, azeliragon was generally well‐ tolerated with similar incidences of treatment‐emergent adverse events overall and by system organ class (SOC) in both treatment groups.

Conclusions

The study failed to meet its primary objective with no statistically significant treatment differences on the ADAS‐cog14 primary endpoint. Results for primary and secondary efficacy outcome measures, as well as safety measures, will be presented.