# Combination anti-amyloid therapy for preclinical Alzheimer's disease

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $8,732,454

## Abstract

PROJECT SUMMARY
This is a multi-PI application for an R01 award under PAR-18-513. The proposed project titled
“Combination Anti-Amyloid Therapy in Preclinical Alzheimer's Disease” is a multicenter randomized
placebo-controlled two arm clinical trial of a combination anti-amyloid therapy: an anti-fibrillar amyloid
antibody for the initial 18 months combined with BACE inhibition therapy for 4 years, in preclinical AD,
defined as asymptomatic individuals with elevated brain amyloid as determined by florbetapir PET
scanning. The primary outcome will be a cognitive composite (a modified version of the Preclinical
Alzheimer's Cognitive Composite, PACC5), with functional and clinical assessments along with
volumetric MR and tau PET as secondary outcomes (and, in a subset, CSF biomarkers). The specific
Aims of the proposed study are; 1. to evaluate the impact of a combination anti-amyloid regimen on
fibrillar amyloid in brain as indicated by amyloid PET SUVr, 2. to evaluate the efficacy and safety of a
combination anti-amyloid regimen in individuals with preclinical AD, and 3. to evaluate the impact of the
combination anti-amyloid regimen on AD biomarkers. Drs. Sperling and Aisen will share responsibility
for scientific oversight of the clinical design and execution of the study and Imaging oversight will be
provided by Dr. Johnson. The ACTC will provide the administrative and operational support, data
capture and data management, clinical monitoring and site management, safety oversight, biostatistical
support, and biomarker sample processing storage and support. Final selection of therapeutic agents
for this trial will be made by a compound selection committee composed of field experts. Committee
membership will include external experts in AD drug development and AD neurobiology, appointed in
concert with NIA. The study team will work collaboratively with the pharmaceutical company
researchers who have clinical experience with these therapeutics in development.
This will be the first study of its kind: a potentially synergistic combination approach to dramatically
reducing amyloid from asymptomatic individuals on the AD spectrum. Combination therapy trials are
increasingly proposed by investigators and regulators to improve the likelihood of success in trials
aiming for disease-modification. This approach could ultimately prevent the onset of AD symptoms

## Key facts

- **NIH application ID:** 9786200
- **Project number:** 5R01AG061848-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Paul S. Aisen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,732,454
- **Award type:** 5
- **Project period:** 2018-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9786200

## Citation

> US National Institutes of Health, RePORTER application 9786200, Combination anti-amyloid therapy for preclinical Alzheimer's disease (5R01AG061848-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9786200. Licensed CC0.

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