TRAILBLAZER-ALZ 2
Trial question
What is the role of donanemab in patients with early symptomatic Alzheimer's disease with amyloid and tau pathology?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
57.0% female
43.0% male
N = 1736
1736 patients (996 female, 740 male).
Inclusion criteria: patients with early symptomatic Alzheimer's disease with amyloid and low/medium or high tau pathology based on PET.
Key exclusion criteria: presence of amyloid-related imaging abnormalities of edema/effusion; > 4 cerebral microhemorrhages; > 1 area of superficial siderosis; any intracerebral hemorrhage > 1 cm or severe white matter disease on MRI.
Interventions
N=860 donanemab (intravenous administration of 1,400 mg every 4 weeks for up to 72 weeks).
N=876 placebo (matching placebo intravenous administration every 4 weeks for up to 72 weeks).
Primary outcome
Decline in least-squares mean integrated Alzheimer Disease Rating Scale score at week 76
10.19 points
13.11 points
13.1 points
9.8 points
6.6 points
3.3 points
0.0 points
Donanemab
Placebo
Significant
decrease ▼
Significant decrease in decline in least-squares mean integrated Alzheimer Disease Rating Scale score at week 76 (10.19 points vs. 13.11 points; AD -2.92 points, 95% CI -1.51 to -4.33).
Secondary outcomes
Significantly lower reduction in Clinical Dementia Rating Scale score at week 76 (1.72 points vs. 2.42 points; AD -0.7 points, 95% CI -0.95 to -0.45).
Significantly lower reduction in 13-item cognitive subscale of Alzheimer Disease Assessment Scale score at week 76 (5.46 points vs. 6.79 points; AD -1.33 points, 95% CI -2.09 to -0.57).
Significant increase in decline in Alzheimer Disease Cooperative Study-Instrument Activities of Daily Living score at week 76 (-4.42 points vs. -6.13 points; AD 1.7 points, 95% CI 0.84 to 2.57).
Safety outcomes
No significant differences in death, serious adverse events.
Conclusion
In patients with early symptomatic Alzheimer's disease with amyloid and low/medium or high tau pathology based on PET, donanemab was superior to placebo with respect to decline in least-squares mean integrated Alzheimer Disease Rating Scale score at week 76.
Reference
John R Sims, Jennifer A Zimmer, Cynthia D Evans et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023 Aug 8;330(6):512-527.
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