Evaluation of Flortaucipir (18F) PET Imaging for Diagnostic Enhancement in Patients with Mild Cognitive Impairment and Dementia

The primary objective of this study is to assess the value of **tau PET** as a diagnostic tool in clinical practice to improve diagnostic accuracy, patient management, and patient wellbeing in individuals with mild cognitive impairment and dementia. This is clinically relevant as enhancing diagnostic precision can lead to better-targeted treatments and improved outcomes for patients experiencing cognitive decline.

Secondary objectives include comparing the diagnostic performance of **tau PET** against combinations of less expensive and more accessible diagnostic tools. This comparison aims to evaluate the cost-effectiveness and practicality of **tau PET** in routine clinical settings.

The clinical trial involves participants diagnosed with **mild cognitive impairment** and dementia, focusing on individuals aged 50 years or older. Both male and female subjects are included, and the study does not target a vulnerable population. The total number of participants is not provided by the sponsor. Participants were selected based on specific criteria, including being in the prodromal stage with subjective and/or objective cognitive impairment and a Clinical Dementia Rating (CDR) score of 0.5, or in the mild dementia stage with a CDR score of 1. All participants must have completed a routine work-up, including basic cognitive screening tests and MRI scanning with a 3DT1 sequence. The study population is characterized by substantial diagnostic uncertainty after routine dementia screening, with Alzheimer's disease being part of the differential diagnosis. Participants must be deemed capable of tolerating study procedures and competent to make informed decisions regarding their participation, as assessed by the attending neurologist. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed to evaluate the diagnostic utility of **tau PET** imaging in patients with **mild cognitive impairment** and **dementia**. This study employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. The trial is expected to commence on December 1, 2023, and conclude by December 1, 2026, with the primary objective of assessing the impact of tau PET on diagnostic accuracy, patient management, and wellbeing.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (50 years or older), cognitive impairment stage, and diagnostic uncertainty. Following the screening, eligible participants will be randomized to receive either the investigational product, **Flortaucipir**, administered as a **solution for injection** via **intravenous bolus injection/IV infusion**, or a control intervention. The maximum daily dose is set at 370 MBq/µg, with a treatment period limited to one day.

Subsequent follow-up visits will be scheduled to monitor changes in diagnosis, clinician confidence, patient management, and wellbeing, comparing pre- and post-tau PET assessments. These visits will also evaluate the performance of tau PET against novel blood-based biomarkers and AI-based classifiers. The end-of-study visit will mark the completion of the trial, where final assessments will be conducted to gather comprehensive data on the primary and secondary endpoints.

Participant involvement is anticipated to last for the duration of the trial, with conditions for early termination including the inability to tolerate study procedures or withdrawal of consent. The trial aims to provide valuable insights into the role of tau PET in clinical practice, potentially influencing future diagnostic and therapeutic strategies for cognitive disorders.

The clinical trial involves the use of **Flortaucipir (18F)**, a radiopharmaceutical agent, as the experimental medication. **Flortaucipir (18F)** is provided in the form of a **solution for injection**. The pharmaceutical form is specifically designed for administration via **intravenous bolus injection or IV infusion**. The maximum daily dose and total dose for the treatment period is 370 megabecquerels (MBq) per microgram. The treatment period is limited to a single day. The active substance, **Flortaucipir (18F)**, is of chemical origin and is manufactured by Eli Lilly and Company Limited. The product is not formulated for pediatric use and is not classified as an orphan drug.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on assessing the diagnostic value of tau PET imaging using **Flortaucipir (18F)**. Participant compliance with the dosing schedule is monitored to ensure accurate administration and to maintain the integrity of the trial data. The trial aims to evaluate the efficacy of tau PET as a diagnostic tool in clinical practice, with the objective of enhancing diagnostic accuracy, patient management, and overall patient wellbeing.

Efficacy in the clinical trial titled "The clinical value of tau PET in the memory clinic (TAP-TAU)" will be assessed using several primary endpoints. These include the change in diagnosis before and after the tau PET scan, specifically in diagnostic categories such as Alzheimer's Disease (AD), non-AD with specified underlying pathology, and mixed AD/non-AD pathology. Additionally, the trial will evaluate the change in clinician confidence regarding the etiological diagnosis, measured on a continuous scale from 0-100%, with a baseline requirement of less than 85%. Changes in patient management, such as adjustments in ancillary investigations, medication, and care, will also be assessed, along with the potential influence on hypothetical prescriptions of disease-modifying treatments for AD. Furthermore, the trial will measure changes in patient wellbeing, focusing on anxiety, uncertainty, and behavioral intentions, as well as post-tau PET perceptions and understanding.

Secondary endpoints will involve comparing the performance of tau PET with novel blood-based biomarkers and artificial intelligence (AI) based classifiers. The efficacy parameters will be collected and analyzed by comparing pre- and post-tau PET data, with a control group comparison conducted after one year. The trial aims to improve diagnostic accuracy, patient management, and wellbeing through the use of tau PET as a diagnostic tool in clinical practice.