Trial results for a follow-on study of donanemab (TRAILBLAZER-EXT, NCT04640077) in participants with Alzheimer's disease were posted on ClinicalTrials.gov on 2025-06-13. The study primarily aimed to validate remote neuropsychological assessments, showing high intraclass correlation coefficients (ICCs) ranging from 0.8172 to 0.8819 between on-site and video teleconference assessments. Safety data indicated that 90.9% of participants experienced one or more treatment-emergent adverse events.
Background
The TRAILBLAZER-EXT study, officially titled "A Follow-On Study of Donanemab (LY3002813) With Video Assessments in Participants With Alzheimer's Disease," aimed to further assess the safety and efficacy of donanemab in individuals with Alzheimer's disease. A key objective was also to validate the administration of neuropsychological assessments via videoconferencing.
Trial design
The TRAILBLAZER-EXT study (NCT04640077) was a Phase 2 follow-on study that enrolled 95 participants. The study investigated donanemab in individuals diagnosed with Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, and Cognitive Impairment. The trial had two main parts: Part A focused on the validation of remote scale assessments, and Part B explored the safety and effectiveness of donanemab.
Key results
The trial reported several key measurements across its two parts. For Part A, which focused on the validation of remote scale assessments, the intraclass correlation coefficients (ICCs) between on-site and video teleconference (VTC) assessments were reported as 0.8172, 0.8819, 0.8251, and 0.8254. These values indicate a strong correlation between the two assessment methods.
For Part B, which involved participants receiving donanemab, safety and cognitive outcomes were measured:
- The percentage of participants with one or more treatment-emergent adverse events (TEAEs) was 90.9%.
- The percentage of participants with one or more serious adverse events (SAEs) was 29.1%.
- Regarding suicidality based on the Columbia-Suicide Severity Rating Scale (C-SSRS), 3 participants were reported for one outcome, and 1 participant for another.
Changes from baseline on cognitive and functional scales for participants on donanemab included:
- Mini Mental State Examination (MMSE) score: a least squares mean change of -0.87 (Standard Error: 0.557).
- Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) score: a least squares mean change of 4.63 (Standard Error: 1.195).
- Integrated Alzheimer's Disease Rating Scale (iADRS): a least squares mean change of -10.14 (Standard Error: 1.850).
- Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL): a least squares mean change of -6.21 (Standard Error: 1.149).
What this means
The results from the TRAILBLAZER-EXT study provide important data on the feasibility of remote neuropsychological assessments for Alzheimer's disease, with the high intraclass correlation coefficients suggesting that video teleconferencing can be a reliable method. This could have implications for future clinical trials and patient monitoring, potentially increasing accessibility and reducing burden. The safety profile for donanemab in this follow-on study shows a high incidence of treatment-emergent adverse events, which is consistent with the known safety considerations for amyloid-beta targeting therapies. The reported changes in cognitive and functional scales offer further insights into the drug's effects, though without a comparator arm, these changes are descriptive.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04640077, titled "A Follow-On Study of Donanemab (LY3002813) With Video Assessments in Participants With Alzheimer's Disease (TRAILBLAZER-EXT)," were posted on 2025-06-13 on clinicaltrials.gov.