Phase 1 Evaluation of [18F]ACI-19626 as a PET Radioligand for Imaging TDP-43 Inclusions in Alzheimer's, ALS, FTD, and LATE Patients Compared to Healthy Controls

The primary objective of this Phase 1 study is to evaluate **[18F]ACI-19626** as a potential PET radioligand for imaging TDP-43 inclusions in the brain. This is clinically relevant as TDP-43 inclusions are associated with several neurodegenerative conditions, including **Alzheimer's Disease**, **Familial and sporadic Amyotrophic lateral sclerosis**, **Familial and sporadic Frontotemporal dementia**, and **Suspected limbic predominant age-related TDP-43 Encephalopathy (LATE)**. Accurate imaging of TDP-43 inclusions could enhance diagnostic precision and facilitate the development of targeted therapies for these conditions. The study will compare patients with suspected TDP-43 proteinopathies to healthy controls to assess the efficacy of the radioligand.

The clinical trial involves participants diagnosed with **Alzheimer's Disease**, familial and sporadic **Amyotrophic lateral sclerosis**, familial and sporadic **Frontotemporal dementia**, and suspected limbic predominant age-related TDP-43 Encephalopathy (LATE). The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The trial population is noted to include a vulnerable population, although specific details regarding the selection process or lifestyle considerations such as diet, physical activity, or habits are not provided. The sponsor has not disclosed the total number of participants involved in the study.

The clinical trial is a **Phase 1** study designed to evaluate the potential of **[18F]ACI-19626** as a PET radioligand for imaging TDP-43 inclusions in the brain. The study will involve patients with suspected TDP-43 proteinopathies, including **Alzheimer's Disease**, **Familial and sporadic Amyotrophic lateral sclerosis**, **Familial and sporadic Frontotemporal dementia**, and **Suspected limbic predominant age-related TDP-43 Encephalopathy (LATE)**, compared with healthy controls. The trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the researchers know who is receiving the treatment or the placebo, thus minimizing bias.

The trial is expected to commence recruitment on November 1, 2024, and conclude by November 1, 2026. Participants will be involved in the study for a duration that includes an initial screening visit, multiple follow-up visits, and an end-of-study visit. The screening visit will determine eligibility based on specific inclusion and exclusion criteria. Follow-up visits will be scheduled to monitor the participants' response to the radioligand and to collect data on its imaging efficacy and safety. The end-of-study visit will assess the overall outcomes and any long-term effects of the radioligand.

Participant involvement is anticipated to last throughout the trial duration unless early termination is warranted. Conditions for early termination may include adverse reactions, withdrawal of consent, or any other medical or ethical reasons deemed necessary by the study investigators. The trial's design and procedures are meticulously planned to ensure the collection of reliable data while prioritizing participant safety and adherence to ethical standards.

In this clinical trial, the experimental medication and non-experimental treatments have not been specified in the provided data. Therefore, a detailed description of the experimental medication, including its name, pharmaceutical form, dosage, route, and frequency of administration, cannot be provided. Similarly, information regarding any non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatment, is not available.

Due to the lack of specific data, additional relevant information about drug administration, dosing schedules, and participant compliance monitoring cannot be detailed. The absence of this information precludes the provision of a comprehensive description of the treatments used in this clinical trial.

The clinical trial is designed to assess efficacy through a structured evaluation process. The trial is categorized as a Phase 1 study, indicating an early stage of clinical research primarily focused on safety and dosage. The estimated recruitment start date is November 1, 2024, with an anticipated end date of November 1, 2026. Although specific efficacy parameters such as primary or secondary endpoints are not detailed, typical Phase 1 trials often involve preliminary assessments of efficacy alongside safety evaluations. These assessments may include the use of validated scales, laboratory tests, or patient-reported outcomes to measure potential therapeutic effects. The schedule for measuring and collecting efficacy data is not specified, but it is common in such trials to have multiple timepoints throughout the study duration to monitor changes and trends. The analysis of collected data will likely involve statistical methods appropriate for early-phase trials, focusing on identifying any initial signs of efficacy that warrant further investigation in subsequent trial phases.