J2O-MC-EKBC: KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Once-Daily LY3473329 in Adults with Elevated Lipoprotein(a) at High Risk for Cardiovascular Events

The primary objective of this study is to evaluate the **efficacy** and **safety** of the investigational drug LY3473329 in adult participants with elevated **Lipoprotein(a)**, who are at high risk for cardiovascular events. This is clinically relevant as elevated Lipoprotein(a) is a known risk factor for cardiovascular diseases, and effective management could potentially reduce the incidence of such events, improving patient outcomes.

The clinical trial involves a total of **133 participants** diagnosed with **lipoprotein disorder**. The study population comprises both male and female adults, aged 40 years and older, who are at high risk for cardiovascular events due to elevated lipoprotein(a) levels. Participants were selected based on specific health conditions, including coronary artery disease, stroke, peripheral artery disease, familial hypercholesterolemia, or type 2 diabetes. The trial includes individuals with a body mass index ranging from 18.5 to 40 kg/m². Participants are required to maintain a stable regimen of certain medications, such as lipid-lowering drugs and hormonal treatments, throughout the study. Both genders are included, with females of childbearing potential agreeing to use highly effective contraception methods. The trial also considers vulnerable populations, ensuring comprehensive representation within the study cohort.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of the investigational drug **LY3473329** in adult participants with elevated **lipoprotein(a)** levels who are at high risk for cardiovascular events. The trial will involve the administration of LY3473329 in the form of a **film-coated tablet** taken orally, with a maximum daily dose of 240 mg and a total treatment period of 12 weeks. The study will also include a placebo group to match LY3473329, ensuring the integrity of the double-blind design.

Participants will be involved in the study for approximately 12 weeks, with the trial expected to conclude by August 2024. The sequence of study visits will begin with an inclusion (screening) visit, where eligibility criteria will be assessed. Key inclusion criteria include being at least 40 years old, having a lipoprotein(a) level of ≥175 nmol/L, and having a history of coronary artery disease, stroke, peripheral artery disease, familial hypercholesterolemia, or type 2 diabetes. Participants must also maintain a stable regimen of certain medications, such as lipid-lowering drugs, throughout the study period. The screening visit will be followed by regular follow-up visits to monitor the participants' health and response to the treatment. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted.

Participants may be withdrawn from the study if they experience adverse events that compromise their safety, fail to comply with the study protocol, or if the investigator deems it necessary for any other reason. The primary endpoint of the study is the percent change from baseline in lipoprotein(a) levels from baseline to week 12. The trial is categorized as a Phase II study, focusing on a non-authorized investigational medicinal product to assess its safety and efficacy in the target population.

The clinical trial involves the administration of the experimental medication **LY3473329**, a synthetic small molecule developed by Eli Lilly and Company Limited. This investigational drug is provided in the form of a **film-coated tablet**. The active substance, LY3473329, is of chemical origin. Participants in the study will receive the medication orally, with a maximum daily dose of 240 mg. The total dose over the course of the treatment period, which spans up to 12 weeks, should not exceed 20,160 mg. The dosing schedule is once daily, and participant compliance will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the appearance of the LY3473329 film-coated tablet, ensuring that neither the participants nor the investigators can distinguish between the active treatment and the placebo. The placebo is administered orally with the same frequency and dosing schedule as the experimental medication, maintaining the integrity of the study's blinding process.

The efficacy of the investigational medicinal product **LY3473329** will be assessed in a Phase 2, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the percent change from baseline in **Lipoprotein(a)** [Lp(a)] levels, measured from baseline to Week 12. This endpoint is selected to determine the impact of LY3473329 on Lp(a) levels in adults with elevated Lp(a) who are at high risk for cardiovascular events.

Measurements of Lp(a) levels will be conducted at specified time points, including baseline and Week 12, to capture the changes over the treatment period. The data collection will involve laboratory tests to ensure accurate and reliable measurement of Lp(a) levels. The analysis will focus on comparing the percent change in Lp(a) levels between the treatment group receiving LY3473329 and the placebo group, providing insights into the efficacy of the investigational product in reducing Lp(a) levels.