ClinicalTrials.gov reported primary completion on 14 April 2023 for a Phase 3 study of donanemab in participants with early Alzheimer’s disease. In the overall population, the least-squares mean change on the iADRS was -10.19 points with donanemab versus -13.11 points with placebo; the listed between-group difference was 2.92 points with a 95% confidence interval of 1.508–4.331 and p=0.001.

Background

The trial evaluated donanemab, also identified in the study record as LY3002813, in participants with early Alzheimer’s disease. Its stated purpose was to assess the study drug’s safety and effectiveness. The registered interventions were donanemab and placebo. The record also described an open-label donanemab safety cohort and a three-year follow-up addendum for participants who received donanemab in the main study; no study drug was administered during that follow-up.

Trial design

TRAILBLAZER-ALZ 2 was a Phase 3 study enrolling 1,736 participants with Alzheimer disease. The registry listed the study status as active, not recruiting. The supplied record did not include primary outcome entries, but it reported measurements for the Integrated Alzheimer’s Disease Rating Scale (iADRS), Mini Mental State Examination (MMSE), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) in the overall population and an intermediate low-medium tau population.

Key results

In the overall population, iADRS change was -10.19 points with donanemab, with a standard error of 0.53, compared with -13.11 points and a standard error of 0.50 with placebo. The mixed-model analysis listed a least-squares mean change difference of 2.92 points, a 95% confidence interval of 1.508–4.331, and p=0.001.

For MMSE in the overall population, the least-squares mean changes were -2.47 points with donanemab and -2.94 points with placebo. For ADAS-Cog13, the corresponding changes were 5.46 points and 6.79 points. The record also listed overall-population mixed-model differences of 0.47 points with a 95% confidence interval of 0.104–0.841 and p=0.012, and 0.48 points with a 95% confidence interval of 0.089–0.868 and p=0.016.

In the intermediate low-medium tau population, iADRS changes were -6.02 points with donanemab and -9.27 points with placebo. MMSE changes were -1.61 points and -2.09 points, while ADAS-Cog13 changes were 3.17 points and 4.69 points, respectively.

What this means

The reported measurements favored donanemab over placebo for the listed cognitive and integrated disease-assessment changes in both the overall and intermediate low-medium tau populations. The supplied record did not include an adverse-event summary, so it does not support a comparative safety conclusion.

Source

Source: ClinicalTrials.gov, trial-results record for NCT04437511, associated with the 14 April 2023 primary-completion event. The registry record is available at clinicaltrials.gov/study/NCT04437511.