GRADUATE I
Trial question
What is the role of gantenerumab in patients with early Alzheimer's disease?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
55.0% female
45.0% male
N = 984
984 patients (545 female, 439 male).
Inclusion criteria: patients, 50-90 years of age, with MCI or mild dementia due to Alzheimer's disease and evidence of amyloid plaques.
Key exclusion criteria: receipt of anticoagulants or GV-971; clinically significant findings on MRI at screening that could cause cognitive impairment.
Interventions
N=499 gantenerumab (target level of 510 mg every 2 weeks).
N=485 placebo (matching placebo).
Primary outcome
Improvement in Clinical Dementia Rating scale-Sum of Boxes score at week 116
3.35 points
3.65 points
3.6 points
2.7 points
1.8 points
0.9 points
0.0 points
Gantenerumab
Placebo
No significant
difference ↔
No significant difference in improvement in Clinical Dementia Rating scale-Sum of Boxes score at week 116 (3.35 points vs. 3.65 points; AD -0.31 points, 95% CI -0.66 to 0.05).
Secondary outcomes
No significant difference in improvement in 13-item cognitive subscale of Alzheimer's Disease Assessment Scale score at week 116 (8.57 points vs. 9.82 points; AD -1.25 points, 95% CI -2.52 to 0.02).
No significant difference in reduction in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory total score at week 116 (-11.21 points vs. -12.32 points; AD 1.11 points, 95% CI -0.48 to 2.7).
Significantly smaller improvement in Functional Activities Questionnaire score at week 116 (7.28 points vs. 8.13 points; AD -0.86 points, 95% CI -1.68 to -0.03).
Safety outcomes
No significant difference in adverse and serious adverse events.
Conclusion
In patients, 50-90 years of age, with MCI or mild dementia due to Alzheimer's disease and evidence of amyloid plaques, gantenerumab was not superior to placebo with respect to improvement in Clinical Dementia Rating scale-Sum of Boxes score at week 116.
Reference
Randall J Bateman, Janice Smith, Michael C Donohue et al. Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease. N Engl J Med. 2023 Nov 16;389(20):1862-1876.
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