Efficacy and Safety Evaluation of MK-1167 as Adjunctive Therapy in Mild to Moderate Alzheimer's Disease Dementia: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to assess the **efficacy** of MK-1167 as an adjunctive therapy to acetylcholinesterase inhibitors on the ADAS-Cog11 Total Score compared with placebo at Week 24. This is clinically relevant as it aims to determine the potential cognitive benefits of MK-1167 in patients with mild to moderate Alzheimer's disease dementia, potentially offering a new therapeutic option to improve cognitive function in this population. Additionally, the study aims to evaluate the safety and tolerability of MK-1167 when used in conjunction with acetylcholinesterase inhibitors.

Secondary objectives include:

• Assessing the efficacy of MK-1167 as adjunctive therapy to acetylcholinesterase inhibitors on the ADCS-CGIC Overall Score compared with placebo at Week 24.
• Evaluating the efficacy of MK-1167 on the ADCS-ADL Total Score as compared with placebo at Week 24.
• Assessing the efficacy of MK-1167 as adjunctive therapy on the ADAS-Cog11 Total Score compared with placebo at Week 12.
• Evaluating the efficacy of MK-1167 on the ADCS-CGIC Overall Score compared with placebo at Week 12.
• Assessing the efficacy of MK-1167 on the ADCS-ADL Total Score as compared with placebo at Week 12.

The clinical trial involves a total of **271 participants** diagnosed with **Alzheimer’s disease dementia**, specifically those in mild to moderate stages (Stage 4 or Stage 5) as per the Alzheimer’s Association Revised Criteria. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. Participants are required to have a Mini-Mental State Examination (MMSE) score between 12 and 24, indicating mild to moderate cognitive impairment. All participants are currently undergoing therapy with acetylcholinesterase inhibitors for the management of their condition. The trial does not include a vulnerable population. Each participant must have a designated study partner capable of providing comprehensive information regarding the participant's daily functioning, cognitive performance, and general health status. The selection process ensures that participants meet these criteria to assess the efficacy and safety of MK-1167 as an adjunctive therapy. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **placebo-controlled**, **double-blind**, parallel-group study to evaluate the efficacy and safety of MK-1167 as an adjunctive therapy in participants with mild to moderate **Alzheimer's disease dementia**. The trial aims to assess the efficacy of MK-1167 in conjunction with acetylcholinesterase inhibitors on the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) Total Score compared with placebo at Week 24. Additionally, the safety and tolerability of MK-1167 will be evaluated. The trial is expected to commence recruitment on April 1, 2025, and conclude by July 20, 2027, with an estimated duration of 24 weeks for each participant's involvement.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having mild to moderate Alzheimer's disease dementia, a Mini-Mental State Examination (MMSE) score of 12 to 24, and current use of acetylcholinesterase inhibitors. A designated study partner is also required to provide information about the participant's overall function and behavior. Following the screening, participants will be randomized to receive either MK-1167 or a placebo, administered orally in capsule form. The study includes follow-up visits at regular intervals to monitor changes in cognitive function and assess any adverse events. The primary endpoint is the change from baseline in the ADAS-Cog11 Total Score at Week 24, while secondary endpoints include the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall Score and changes in the ADCS-ADL Total Score at Weeks 12 and 24.

The end-of-study visit will occur at the conclusion of the 24-week treatment period, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events or if they discontinue the study intervention due to such events. The trial is not classified as low intervention and is categorized as a Phase II study focusing on safety, efficacy, and dosing regimen in the target population. The investigational product, MK-1167, is a chemical compound provided in capsule form by Merck & Co. Inc., and the study will utilize a placebo comparator to ensure the integrity of the double-blind design.

The clinical trial involves the administration of **MK-1167**, an experimental medication developed by Merck & Co. Inc. **MK-1167** is provided in a **capsule** form and is intended for **oral** administration. The active substance, also named **MK-1167**, is of chemical origin. The trial does not specify a maximum daily dose or total dose amount, and the treatment period is limited to one week. The medication is not formulated for pediatric use, and it is not classified as an orphan drug. The primary objective of the trial is to evaluate the efficacy and safety of **MK-1167** as an adjunctive therapy in participants with mild to moderate Alzheimer's disease dementia.

In addition to the experimental medication, a **placebo** is utilized in the study to serve as a comparator. The placebo is designed to mimic the appearance of the **MK-1167** capsule but does not contain any active substance. The use of a placebo allows for a double-blind, randomized, and controlled assessment of the experimental drug's efficacy and safety. The placebo is administered in the same manner as the experimental medication, ensuring consistency in the trial's methodology.

The efficacy of the investigational product **MK-1167** in the clinical trial will be assessed primarily through the change from baseline in the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) Total Score at Week 24. This endpoint is designed to evaluate the cognitive function of participants with mild to moderate Alzheimer's Disease dementia. Secondary efficacy endpoints include the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall Score and the change from baseline in the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total Score, both assessed at Weeks 12 and 24.

The ADAS-Cog11 is a widely used and validated tool for measuring cognitive performance in Alzheimer's Disease, while the ADCS-CGIC and ADCS-ADL scales provide insights into the overall clinical impression of change and daily living activities, respectively. These assessments will be conducted at specified timepoints to ensure a comprehensive evaluation of the treatment's impact over the course of the study. The data collected will be analyzed to determine the efficacy of MK-1167 as an adjunctive therapy to acetylcholinesterase inhibitors compared to placebo.