A Study of LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to evaluate the efficacy and safety of LY3473329 in adult participants with elevated Lp(a) at high risk for cardiovascular events.

Official Title
-----------------
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

Conditions
-----------------
Lipoprotein Disorder

Intervention / Treatment
-----------------
* Drug: LY3473329
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be at least 40 years old Participants with Lp(a) ≥175 nmol/L at randomization, measured at the central laboratory. High risk for cardiovascular events defined as documented coronary artery disease (CAD), stroke, or peripheral artery disease or atherosclerotic cardiovascular disease (ASCVD) risk equivalents (familial hypercholesterolemia or type 2 diabetes). Participants on the following medications according to local practice must be on a stable regimen for at least 4 weeks prior to randomization and expected to remain on a stable regimen through the end of the post-treatment follow-up period. lipid-lowering drugs testosterone, estrogens, anti-estrogens, progestins, selective estrogen receptor modulators, or growth hormone Have a body mass index within the range 18.5 to 40 kilogram/square meter (kg/m²), inclusive. Males who agree to use highly effective or effective methods of contraception may participate in this trial. Women of childbearing potential (WOCBP) who agree to use highly effective or effective methods of contraception and women not of childbearing potential (WNOCBP) may participate in this trial. Exclusion Criteria: Have a history or presence of an underlying disease, or surgical, physical, medical, or psychiatric condition that, in the opinion of the investigator, would potentially affect participant safety within the study or interfere with participating in or completing the study or with the interpretation of data. Any of the following, or other events indicating unstable medical condition in the opinion of the investigator, within 3 months of randomization: major surgery coronary, carotid, or peripheral arterial revascularization stroke or transient ischemic attack myocardial infarction or unstable angina acute limb ischemia Have, in the 6 months prior to day 1, uncontrolled Type 1 or Type 2 diabetes Have uncontrolled hypertension

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3473329 Dose 1<br>Participants will receive LY3473329 orally. | Drug: LY3473329<br>* Administered orally<br>|
| Experimental: LY3473329 Dose 2<br>Participants will receive LY3473329 orally. | Drug: LY3473329<br>* Administered orally<br>|
| Experimental: LY3473329 Dose 3<br>Participants will receive LY3473329 orally. | Drug: LY3473329<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo orally. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Lipoprotein (a) Lp(a) |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Lp(a) <125 Nanomole/Liter (nmol/L) |  | Week 12 | 
| Percent Change from Baseline for Apolipoprotein B (ApoB) |  | Baseline, Week 12 | 
| Percent Change from Baseline for High Sensitivity C-reactive (hsCRP) |  | Baseline, Week 12 | 
| Pharmacokinetics (PK): Trough Concentrations (Ctrough) of LY3473329 | PK Ctrough of LY34723329 will be measured | Baseline to Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cholesterol, Atherosclerotic cardiovascular disease, ASCVD, Dyslipidemia, Lipoprotein(a), Lp(a), Cardiovascular, Cardiovascular disease, Hyperlipidemia