Evaluation of Donanemab, Florbetapir (18F), and Flortaucipir (18F) in Early Symptomatic Alzheimer's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to assess the effect of **donanemab** versus placebo on clinical progression in participants with early symptomatic **Alzheimer's Disease**. This objective is clinically relevant as it aims to evaluate the potential of donanemab to alter the course of Alzheimer's Disease, which could lead to improved management and outcomes for patients in the early stages of this neurodegenerative condition.

The clinical trial involves a total of **1533 participants** diagnosed with **Alzheimer Disease**. The study population includes both male and female subjects, with an age range that encompasses middle-aged to older adults. Participants were selected based on specific criteria, including a gradual and progressive change in memory function reported for at least six months, and a Mini-Mental State Examination (MMSE) score between 20 and 28 at baseline. Additionally, participants were required to meet certain PET scan criteria and have a study partner willing to provide informed consent. The trial population includes individuals from a vulnerable population, reflecting the nature of the disease under investigation. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed to evaluate the **safety**, tolerability, and efficacy of **donanemab** in participants with early symptomatic **Alzheimer's disease**. This is a Phase IV, randomized, double-blind, placebo-controlled study. The trial will involve the administration of **donanemab** and a placebo, both in the form of a **solution for injection** via **infusion**. The study is expected to run from June 2020 to August 2025, with a total duration of approximately five years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as a gradual and progressive change in memory function over at least six months, an MMSE score between 20 and 28, and specific PET scan criteria. Following the screening, eligible participants will be randomized to receive either **donanemab** or a placebo. The trial includes regular follow-up visits to monitor the participants' health and the effects of the treatment. The primary endpoint is the change from baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS).

The expected length of participant involvement is up to 150 days, with the maximum treatment period for **donanemab** being 150 days. Conditions that may lead to early termination from the study include adverse reactions to the treatment or failure to adhere to the study protocol. The end-of-study visit will conclude the trial for each participant, during which final assessments will be conducted to evaluate the overall impact of the treatment. The study aims to provide valuable insights into the potential benefits of **donanemab** in slowing the clinical progression of early symptomatic **Alzheimer's disease**.

**Florbetapir (18F)** is an experimental medication used in this clinical trial. It is provided as a **solution for injection** and is administered via **infusion**. The maximum daily dose is 7.43 mCi, with a total maximum dose of 52.01 mCi over a treatment period of up to 154 days. Florbetapir (18F) is a chemical substance developed by Eli Lilly and Company Limited, and it is not formulated for pediatric use.

The **placebo** used in this study is designed to match the experimental treatments in appearance but contains no active substance. It serves as a comparator to evaluate the efficacy and safety of the experimental medications. The placebo is not associated with any specific pharmaceutical form or route of administration, as it is intended to mimic the experimental treatments.

**Flortaucipir (18F)** is another experimental medication included in the trial. It is also a **solution for injection** administered via **infusion**. The maximum daily dose is 9.1 mCi, with a total maximum dose of 27.3 mCi over a treatment period of up to 154 days. Flortaucipir (18F) is a chemical substance, and like Florbetapir, it is developed by Eli Lilly and Company Limited and is not intended for pediatric use.

**Donanemab** is the primary investigational drug in this trial, provided as a **solution for injection** and administered through **infusion**. The maximum daily dose is 1400 mg, with a total maximum dose of 51100 mg over a treatment period of up to 150 days. Donanemab is a protein-based substance, specifically an antibody directed at amyloid beta, developed by Eli Lilly and Company Limited. It is not formulated for pediatric use.

The efficacy of **Donanemab** in the treatment of early symptomatic Alzheimer's disease will be assessed through a primary endpoint, which is the change from baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) in the overall population. This scale is a validated tool used to measure cognitive and functional performance in individuals with Alzheimer's disease. The assessment will involve comparing the effects of Donanemab to a placebo, with the aim of evaluating the clinical progression in participants. The trial will utilize 18F flortaucipir and 18F florbetapir PET scans as part of the inclusion criteria to ensure appropriate participant selection. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial duration, which is estimated to conclude by August 2025.