A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of ABBV-916 in Subjects with Early Alzheimer's Disease

The primary objective of this study is to evaluate the **safety**, tolerability, and amyloid reduction associated with ABBV-916 after repeated intravenous administrations in subjects with early **Alzheimer's disease**. This is clinically relevant as it aims to assess the potential of ABBV-916 in modifying disease progression by targeting amyloid pathology, which is a hallmark of Alzheimer's disease. The study is designed as a randomized, double-blind, placebo-controlled trial to ensure the reliability and validity of the results.

The clinical trial involves a total of **86 participants** diagnosed with **Alzheimer's disease (AD)**. The study population comprises both male and female adults aged between **50 to 90 years**. Participants were selected based on specific criteria, including adequate premorbid literacy and sensory acuity to complete neuropsychological testing. They must have a Mini-Mental State Examination (MMSE) score ranging from 20 to 28 and demonstrate amyloid pathology through blood-based biomarkers and amyloid PET scans. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The selection process ensures that participants have the necessary cognitive and sensory capabilities to engage in the study effectively.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of **ABBV-916** in subjects with early **Alzheimer's disease**. The trial will involve adult male and female participants aged 50 to 90 years, who meet specific inclusion criteria, such as having an MMSE score of 20 to 28 and amyloid PET scan results consistent with amyloid pathology. The study will be conducted over an estimated duration from June 2023 to March 2027, with the primary objective being to assess the safety, tolerability, and amyloid reduction associated with ABBV-916 after repeated intravenous administrations.

Participants will be involved in the study for a maximum treatment period of 32 weeks. The trial will include several key visits: an initial **screening visit** to determine eligibility, followed by regular **follow-up visits** to monitor safety and efficacy, and an **end-of-study visit** to assess the final outcomes. The primary efficacy endpoint is the change from baseline in brain amyloid plaque deposition at Week 24, as measured by amyloid PET scan. Participants may be withdrawn from the study early if they experience significant adverse effects or if they no longer meet the study criteria.

The investigational product, ABBV-916, is administered as a **solution for injection** and is compared against a placebo. The study also involves the use of **MK-6240**, a radiotracer for imaging purposes. The trial is not classified as a low-intervention study and is categorized as a Phase 2 trial. The study's design ensures that neither the participants nor the investigators know which treatment the participants are receiving, maintaining the integrity of the double-blind methodology.

The clinical trial involves the administration of **MK-6240**, an experimental medication formulated as a **solution for injection**. The active substance in MK-6240 is **florquinitau (18F)**, a chemical compound. The medication is administered via injection, with a maximum daily dose of 185 MBq and a total maximum dose of 740 MBq over a treatment period of up to 32 weeks. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen. MK-6240 is developed by AbbVie Deutschland GmbH & Co. KG.

Another experimental treatment in the study is **ABBV-916**, also formulated as a **solution for injection**. The active substance is a **humanised IgG1 monoclonal antibody against N-terminally truncated pyroglutamate-3 AB**, classified as a protein. ABBV-916 is administered intravenously, with the dosing schedule designed to evaluate its safety and efficacy in reducing amyloid levels in subjects with early Alzheimer's disease. The treatment period extends up to 32 weeks, with careful monitoring of participant compliance and response to the therapy. This investigational product is also developed by AbbVie Deutschland GmbH & Co. KG.

The study includes a **placebo** group to serve as a control for evaluating the effects of the experimental treatments. The placebo is administered in a manner consistent with the experimental medications, ensuring blinding and maintaining the integrity of the study design. The placebo does not contain any active substances and is used to assess the efficacy and safety of the investigational drugs by comparison.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the change from baseline in brain amyloid plaque deposition, specifically the **amyloid centiloid value**, at Week 24. This measurement will be conducted using an amyloid PET scan. The trial is designed as a randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ABBV-916 in subjects with early Alzheimer's disease. The primary objective is to assess the safety, tolerability, and amyloid reduction associated with ABBV-916 after repeated intravenous administrations. The study will include adult male and female participants aged 50 to 90 years, who meet specific inclusion criteria, such as having an MMSE score of 20 to 28 and amyloid PET scan results consistent with amyloid pathology. The trial is estimated to conclude by March 2027, with recruitment having started in June 2023.