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

Eli Lilly and Company320 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

320

Conditions

Lipoprotein Disorder

Interventions

LY3819469DRUG

Administered SC

PlaceboDRUG

Administered SC

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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

Locations (80)

Outcomes

Primary Outcomes

Percent Change From Baseline in Time Averaged Lipoprotein(a) [Lp(a)] Over Days 60-180

LPa levels were assessed using Immuno turbidimetric method. Percent change is calculated as: Percent Change=\[(Lp(a) at Time Point-Lp(a) at Baseline)/Lp(a) at Baseline\]×100 Least squares (LS) mean was determined using mixed model repeated measures (MMRM) model with log(Lp(a)) - log(Baseline) = log(Baseline) + Treatment + Time + Treatment\*Time (Type III sum of squares) as post-baseline measures. Result presented is after back-transformation. Variance-Covariance structure = Unstructured. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable.

Time frame: Baseline, Days 60 - 180

Secondary Outcomes

Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360

LPa levels were assessed using Immuno turbidimetric method. LS mean was determined using MMRM model with log(Lp(a)) - log(Baseline) = log(Baseline) + Treatment + Time + Treatment\*Time (Type III sum of squares) as post-baseline measures.. Result presented is after back-transformation. Variance-Covariance structure = Unstructured. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable.

Time frame: Baseline, Days 240 - 360

Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180

Percentage of Participants Achieving Lp(a) \<125 and \<75 Nanomole/Liter (nmol/L) at Days 60, 180 is reported.

Time frame: Days 60, 180

Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540

Percentage of Participants Achieving Lp(a) \<125 and \<75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540 is reported.

Time frame: Days 240, 360, and 540

Percent Change From Baseline in Lp(a)

Data from ClinicalTrials.gov

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Baltimore, Maryland, United States

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Dorchester, Massachusetts, United States

...and 70 more locations

LS mean was determined using MMRM model with log(Actual Measurement/Baseline) = log (Baseline) + High Risk CV Stratum (yes/no) + Treatment + Time + Treatment\*Time (Type III sum of squares) as post-baseline measures. Variance-Covariance structure (Change from Baseline) = Unstructured. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable.

Time frame: Baseline, Days 60, 180, 240, 360, and 540

Percent Change From Baseline in Apolipoprotein B (ApoB)

LS mean was determined using MMRM model with log (Actual Measurement/Baseline) = log(Baseline) + Baseline Lp(a) stratum (\<275 nmol/L vs. \>=275 nmol/L) + High Risk CV Stratum (yes/no) + Treatment + Time + Treatment\*Time (Type III sum of squares as post-baseline measures. Variance-Covariance structure (Change from Baseline) = Unstructured. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable.

Time frame: Baseline, Days 60, 180, 240, 360, and 540

Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation. LS mean was determined using MMRM model with log (Actual Measurement/Baseline) = log(Baseline) + Baseline Lp(a) stratum (\<275 nmol/L vs. \>=275 nmol/L) + High Risk CV Stratum (yes/no) + Treatment + Time + Treatment\*Time (Type III sum of squares as post-baseline measures. Variance-Covariance structure (Change from Baseline) = Unstructured. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable.

Time frame: Baseline, Days 60, 180, 240, 360, and 540

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3819469

AUC was computed using the population PK model. Therefore, the concentrations are simulated from time 0 to infinity to estimate AUC for each participant. The timeframe reflects the PK timepoints that were collected to develop the population PK. Although this is a multiple dose study, the plasma PK is very short, so AUC0-180days is equivalent to AUC0-infinity.

Time frame: Day 1: 0.5 hours, 4-9 hours post-dose; Day 180: 24-36 hours post-dose