Evaluation of Cerebral Tau Aggregates Using [18F]RO6958948 PET Imaging in Alzheimer's Disease Patients

The primary objective of this study is to **characterize tau tracer retention** using the radioligand [18F]RO6958948 in relation to amyloid levels, both transversally and longitudinally, in individuals at preclinical stages of **Alzheimer's Disease**. This is clinically relevant as it may enhance the understanding of tau pathology progression in the early stages of Alzheimer's Disease, potentially informing early diagnostic and therapeutic strategies.

The clinical trial focuses on individuals diagnosed with **Alzheimer's Disease**. The study population comprises both male and female participants, aged between 45 and 80 years, who have previously participated in BBRC-sponsored studies. The trial does not include a vulnerable population. Participants are required to have a known cognitive status and AB and tau status, as determined by prior BBRC-sponsored studies. Additionally, they must have undergone a cerebral MRI within the last 12 months, which should not indicate any radiological incidental findings that would exclude them from the study. Female participants are required to be post-menopausal or have a negative pregnancy test at the time of PET acquisition. The sponsor has not provided information regarding the total number of participants in the trial. Participants are expected to have a good knowledge of the language and be literate. The selection criteria ensure that the study population is well-defined and relevant to the trial's objectives.

The clinical trial is designed to evaluate the **retention** of a tau tracer, **[18F]RO6958948**, in participants with varying levels of amyloid, both transversally and longitudinally. This study is a Phase IV, randomized, double-blind, controlled trial focusing on individuals with **Alzheimer's Disease**. The trial is expected to run from January 2021 to March 2029, with participant involvement lasting up to one year. The investigational product, a **solution for injection**, is administered via **intravenous bolus injection/IV infusion**. The maximum daily dose is 370 MBq, with a total dose not exceeding 10 micrograms.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, cognitive status, and previous participation in specific studies. The inclusion criteria require participants to have a recent cerebral MRI and known amyloid and tau status. Female participants must be post-menopausal or have a negative pregnancy test at the time of PET acquisition. Follow-up visits will be scheduled to monitor the primary endpoint, which is the global and regional retention rate of the tracer. The end-of-study visit will conclude the participant's involvement, assessing the overall retention and any adverse effects.

Participants may be terminated early from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial aims to provide valuable insights into the relationship between tau tracer retention and amyloid levels, contributing to the understanding of Alzheimer's Disease progression.

The clinical trial involves the administration of the experimental medication **[18F]RO6958948**, a radiolabeled compound used for positron emission tomography (PET) imaging. The active substance in this investigational product is **2-(6-[18F]FLUORO-PYRIDIN-3-YL)-9H-DIPYRIDO[2,3-B:3',4'-D]PYRROLE**. This compound is provided in the pharmaceutical form of a **solution for injection**. The administration route is via **intravenous bolus injection or IV infusion**. The maximum daily dose is set at 370 MBq (megabecquerels), with a total dose not exceeding 10 µg (micrograms) over the course of the treatment period, which is limited to one day. The investigational product is not formulated for pediatric use and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the characterization of cerebral tau aggregates using the investigational tracer. Participant compliance with the dosing schedule is monitored through standard clinical trial procedures, ensuring adherence to the specified administration protocol. The trial aims to characterize tau tracer retention in relation to amyloid levels, both transversally and longitudinally, within the study population.

Efficacy in this clinical trial will be assessed by evaluating the **global and regional retention rate** of the investigational product, [18F]RO6958948, a tau tracer used in PET imaging. The primary endpoint focuses on the characterization of tau tracer retention as a function of amyloid levels, both transversally and longitudinally. This assessment will provide insights into the cerebral tau aggregates in the study population. The trial is designed to measure these parameters using PET imaging techniques, which will allow for precise quantification of tracer retention in the brain. The data collection will occur at specified intervals throughout the trial, ensuring a comprehensive analysis of the tracer's retention patterns over time. The results will be analyzed to determine the efficacy of [18F]RO6958948 in characterizing tau aggregates, contributing to the understanding of its potential role in the context of amyloid levels.