A Study of LY3819469 in Participants With Elevated Lipoprotein(a) [Lp(a)]

Study Overview
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Brief Summary
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The main purpose of this study is to determine the efficacy and safety of LY3819469 in adults with elevated lipoprotein(a). The study will lasts about 20 months.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of LY3819469 in Adults With Elevated Lipoprotein(a)

Conditions
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Lipoprotein Disorder

Intervention / Treatment
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* Drug: LY3819469
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be at least 40 years old at the time of signing the informed consent. Participants with Lp(a) ≥175 nmol/L at screening, measured at the central laboratory Participants on the following medications according to local practice must be on a stable regimen for at least 4 weeks prior to screening and randomization and expected to remain on a stable regimen through the end of the Treatment and Assessment 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. Male and/or Female Males who agree to use highly effective/effective methods of contraception may participate in this trial. 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
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3819469 Dose 1<br>Participants will receive LY3819469 subcutaneously (SC). | Drug: LY3819469<br>* Administered SC<br>|
| Experimental: LY3819469 Dose 2<br>Participants will receive LY3819469 SC. | Drug: LY3819469<br>* Administered SC<br>|
| Experimental: LY3819469 Dose 3<br>Participants will receive LY3819469 SC. | Drug: LY3819469<br>* Administered SC<br>|
| Experimental: LY3819469 Dose 4 + Placebo<br>Participants will receive LY3819469 SC and placebo. | Drug: LY3819469<br>* Administered SC<br>Drug: Placebo<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Time Averaged Lipoprotein(a) [Lp(a)] |  | Baseline, Days 60 - 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Time Averaged Lp(a) |  | Baseline, 240 - 360 | 
| Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (nmol/L) |  | Days 60, 180, 240, 360, and 540 | 
| Percent Change from Baseline in Lp(a) |  | Baseline to Days 60, 180, 240, 360, and 540 | 
| Percent Change from Baseline in Apolipoprotein B (ApoB) |  | Baseline to Days 60, 180, 240, 360, and 540 | 
| Percent Change from Baseline in High-sensitivity C-reactive Protein (hsCRP) |  | Baseline to Days 60, 180, 240, 360, and 540 | 
| Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of LY3819469 | Population PK parameters will be assessed by AUC | Baseline to Day 540 |