Dataset Information

Trial of Solanezumab in Preclinical Alzheimer's Disease.

ABSTRACT:

Background

Trials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results.

Methods

We tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini-Mental State Examination of 25 or more (range, 0 to 30, with lower scores indicating poorer cognition), and elevated brain amyloid levels on ¹⁸F-florbetapir positron-emission tomography (PET) were enrolled. Participants were randomly assigned in a 1:1 ratio to receive solanezumab at a dose of up to 1600 mg intravenously every 4 weeks or placebo. The primary end point was the change in the Preclinical Alzheimer Cognitive Composite (PACC) score (calculated as the sum of four z scores, with higher scores indicating better cognitive performance) over a period of 240 weeks.

Results

A total of 1169 persons underwent randomization: 578 were assigned to the solanezumab group and 591 to the placebo group. The mean age of the participants was 72 years, approximately 60% were women, and 75% had a family history of dementia. At 240 weeks, the mean change in PACC score was -1.43 in the solanezumab group and -1.13 in the placebo group (difference, -0.30; 95% confidence interval, -0.82 to 0.22; P = 0.26). Amyloid levels on brain PET increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group. Amyloid-related imaging abnormalities (ARIA) with edema occurred in less than 1% of the participants in each group. ARIA with microhemorrhage or hemosiderosis occurred in 29.2% of the participants in the solanezumab group and 32.8% of those in the placebo group.

Conclusions

Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease. (Funded by the National Institute on Aging and others; A4 ClinicalTrials.gov number, NCT02008357.).

SUBMITTER: Sperling RA

PROVIDER: S-EPMC10559996 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Trial of Solanezumab in Preclinical Alzheimer's Disease.

Sperling Reisa A RA Donohue Michael C MC Raman Rema R Rafii Michael S MS Johnson Keith K Masters Colin L CL van Dyck Christopher H CH Iwatsubo Takeshi T Marshall Gad A GA Yaari Roy R Mancini Michele M Holdridge Karen C KC Case Michael M Sims John R JR Aisen Paul S PS

The New England journal of medicine 20230717 12

<h4>Background</h4>Trials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results.<h4>Methods</h4>We tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini-Mental State Exam ...[more]

PMID: 37458272

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Dataset Information

Trial of Solanezumab in Preclinical Alzheimer's Disease.

Background

Methods

Results

Conclusions

Publications

Trial of Solanezumab in Preclinical Alzheimer's Disease.

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