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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05565742

Enrollment

320

Registered

2022-10-04

Start date

2022-10-20

Completion date

2024-10-17

Last updated

2025-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lipoprotein Disorder

Brief summary

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.

Interventions

DRUGLY3819469

Administered SC

DRUGPlacebo

Administered SC

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percent Change From Baseline in Time Averaged Lipoprotein(a) [Lp(a)] Over Days 60-180	Baseline, 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.

Secondary

Measure	Time frame	Description
Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Days 60, 180	Percentage of Participants Achieving Lp(a) \<125 and \<75 Nanomole/Liter (nmol/L) at Days 60, 180 is reported.
Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	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.
Percent Change From Baseline in Lp(a)	Baseline, Days 60, 180, 240, 360, and 540	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.
Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360	Baseline, 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.
Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Days 60, 180, 240, 360, and 540	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.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3819469	Day 1: 0.5 hours, 4-9 hours post-dose; Day 180: 24-36 hours post-dose	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.
Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Days 60, 180, 240, 360, and 540	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.

Countries

Argentina, China, Denmark, Germany, Japan, Mexico, Netherlands, Romania, Spain, United States

Participant flow

Participants by arm

Arm	Count
16 mg LY3819469 Participants received 16 mg of LY3819469 on day 1 and day 180, administered as a SC injection.	36
96 mg LY3819469 Participants received 96 mg of LY3819469 on day 1 and day 180, administered as a SC injection.	74
400 mg LY3819469 Participants received 400 mg of LY3819469 on day 1 and day 180, administered as a SC injection.	69
400 mg LY3819469 + Placebo Participants received 400 mg of LY3819469 on day 1 and placebo on day 180, administered as a SC injection.	72
Placebo Participants received placebo on day 1 and day 180, administered as a SC injection.	69
Total	320

Withdrawals & dropouts

Period	Reason	FG000	FG002	FG003	FG004
Overall Study	Death	1	0	0	0
Overall Study	Participant Travelled Abroad	0	0	0	1
Overall Study	Withdrawal by Subject	0	2	2	2

Baseline characteristics

Characteristic	96 mg LY3819469	16 mg LY3819469	Total	Placebo	400 mg LY3819469 + Placebo	400 mg LY3819469
Age, Continuous	63.8 years STANDARD_DEVIATION 9.9	62.6 years STANDARD_DEVIATION 10.55	62.7 years STANDARD_DEVIATION 9.84	63.5 years STANDARD_DEVIATION 8.42	62.2 years STANDARD_DEVIATION 9.65	61.4 years STANDARD_DEVIATION 10.93
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants	7 Participants	44 Participants	2 Participants	17 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants	28 Participants	275 Participants	67 Participants	55 Participants	59 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Lipoprotein(a) [Lp(a)] level	278.86 Nanomole/Liter (nmol/L) STANDARD_DEVIATION 79.53	267.63 Nanomole/Liter (nmol/L) STANDARD_DEVIATION 81.8	274.74 Nanomole/Liter (nmol/L) STANDARD_DEVIATION 89.98	266.62 Nanomole/Liter (nmol/L) STANDARD_DEVIATION 91.31	279.98 Nanomole/Liter (nmol/L) STANDARD_DEVIATION 93.5	276.66 Nanomole/Liter (nmol/L) STANDARD_DEVIATION 100.68
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	2 Participants	5 Participants	0 Participants	2 Participants	1 Participants
Race (NIH/OMB) Asian	13 Participants	3 Participants	47 Participants	10 Participants	8 Participants	13 Participants
Race (NIH/OMB) Black or African American	2 Participants	1 Participants	7 Participants	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	58 Participants	30 Participants	260 Participants	59 Participants	60 Participants	53 Participants
Region of Enrollment Argentina	6 Participants	5 Participants	24 Participants	2 Participants	6 Participants	5 Participants
Region of Enrollment China	3 Participants	0 Participants	10 Participants	3 Participants	3 Participants	1 Participants
Region of Enrollment Denmark	4 Participants	4 Participants	29 Participants	12 Participants	4 Participants	5 Participants
Region of Enrollment Germany	12 Participants	5 Participants	41 Participants	10 Participants	6 Participants	8 Participants
Region of Enrollment Japan	10 Participants	3 Participants	34 Participants	5 Participants	5 Participants	11 Participants
Region of Enrollment Mexico	0 Participants	2 Participants	8 Participants	0 Participants	4 Participants	2 Participants
Region of Enrollment Netherlands	11 Participants	2 Participants	36 Participants	7 Participants	7 Participants	9 Participants
Region of Enrollment Romania	3 Participants	3 Participants	13 Participants	1 Participants	4 Participants	2 Participants
Region of Enrollment Spain	8 Participants	4 Participants	38 Participants	5 Participants	14 Participants	7 Participants
Region of Enrollment United States	17 Participants	8 Participants	87 Participants	24 Participants	19 Participants	19 Participants
Sex: Female, Male Female	35 Participants	9 Participants	138 Participants	32 Participants	27 Participants	35 Participants
Sex: Female, Male Male	39 Participants	27 Participants	182 Participants	37 Participants	45 Participants	34 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	1 / 36	0 / 74	0 / 69	0 / 72	0 / 69
other Total, other adverse events	14 / 36	25 / 74	34 / 69	35 / 72	26 / 69
serious Total, serious adverse events	1 / 36	9 / 74	11 / 69	8 / 72	6 / 69

Outcome results

Primary

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

Population: Full Analysis Set. As specified in the Protocol and statistical analysis plan (SAP), for the primary analysis up to Day 180, the two LY3819469 treatment groups assigned to 400 mg (400 mg LY3819469, 400 mg LY3819469 + placebo) were pooled into one treatment group (400 mg LY3819469 pooled) because participants received the same study intervention in the first 180 days

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
16 mg LY3819469	Percent Change From Baseline in Time Averaged Lipoprotein(a) [Lp(a)] Over Days 60-180	-39.0 percent change	Standard Error 7.37
96 mg LY3819469	Percent Change From Baseline in Time Averaged Lipoprotein(a) [Lp(a)] Over Days 60-180	-74.4 percent change	Standard Error 2.16
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Time Averaged Lipoprotein(a) [Lp(a)] Over Days 60-180	-93.7 percent change	Standard Error 0.38
Placebo	Percent Change From Baseline in Time Averaged Lipoprotein(a) [Lp(a)] Over Days 60-180	3.1 percent change	Standard Error 8.99

p-value: <0.00195% CI: [-55.8, -20.6]Mixed Models Analysis

p-value: <0.00195% CI: [-80.4, -68.5]Mixed Models Analysis

p-value: <0.00195% CI: [-95.1, -92.5]Mixed Models Analysis

Secondary

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

Population: Efficacy Analysis Set. Overall Number of Participants Analyzed = number of participants in each group. Number Analyzed = participants with available data at specified time points.

Arm	Measure	Group	Value (NUMBER)
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 540	9.38 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 240	36.36 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 540	0.00 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 240	18.18 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 360	6.06 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 360	24.24 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 540	32.31 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 360	58.82 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 360	41.18 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 240	88.06 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 240	76.12 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 540	16.92 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 240	96.83 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 360	82.54 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 540	45.90 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 360	88.89 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 540	75.41 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 240	98.41 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 540	35.48 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 240	78.79 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 360	59.38 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 240	65.15 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 360	42.19 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 540	16.13 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 360	0.00 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 540	0.00 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 360	0.00 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <125 nmol/L: Day 240	1.56 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 240	1.56 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 240, 360, and 540	Lp(a) <75 nmol/L: Day 540	0.00 percentage of participants

Comparison: Lp(a) \<125 nmol/L: Day 240p-value: <0.00195% CI: [5.36, 191.58]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 240p-value: <0.00195% CI: [95.36, 3805.22]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 240p-value: <0.00195% CI: [527.56, 91646.24]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 240p-value: <0.00195% CI: [57.46, 2104.62]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 360p-value: 0.00795% CI: [2.98, 1015.84]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 360p-value: <0.00195% CI: [20.83, 6332.68]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 360p-value: <0.00195% CI: [150.95, 57790.71]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 360p-value: <0.00195% CI: [21.46, 6571.66]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 540p-value: 0.06895% CI: [0.81, 331.69]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 540p-value: 0.00295% CI: [4.99, 1447.48]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 540p-value: <0.00195% CI: [33.99, 10405.09]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 540p-value: 0.00195% CI: [6.47, 1875.77]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 240p-value: 0.0195% CI: [1.81, 74.29]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 240p-value: <0.00195% CI: [39.92, 1362.79]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 240p-value: <0.00195% CI: [331.26, 28778.1]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 240p-value: <0.00195% CI: [25.2, 829.42]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 360p-value: 0.12595% CI: [0.51, 243.85]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 360p-value: <0.00195% CI: [8.64, 2546.89]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 360p-value: <0.00195% CI: [77.76, 26349.86]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 360p-value: <0.00195% CI: [8.6, 2538.95]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 540p-value: 0.73395% CI: [0.04, 104.02]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 540p-value: 0.01595% CI: [1.98, 594.46]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 540p-value: <0.00195% CI: [9.4, 2716.42]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 540p-value: 0.01395% CI: [2.19, 659.75]Regression, Logistic

Secondary

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

Population: Efficacy Analysis Set. Overall Number of Participants Analyzed = number of participants in each group. Number Analyzed = participants with available data at specified time points.~As specified in the protocol and SAP, for the primary analysis up to Day 180, two LY3819469 treatment groups assigned to 400 mg (400 mg LY3819469,400 mg LY3819469 + placebo) were pooled into one treatment group (400 mg LY3819469 pooled) because participants are receiving same study intervention in the first 180 days.

Arm	Measure	Group	Value (NUMBER)
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 60	37.14 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 180	14.29 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 60	14.29 percentage of participants
16 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 180	8.57 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 180	58.33 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 60	64.38 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 180	33.33 percentage of participants
96 mg LY3819469	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 60	86.30 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 60	96.35 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 180	90.15 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 180	81.06 percentage of participants
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 60	97.81 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 180	0.00 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 180	0.00 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <125 nmol/L: Day 60	0.00 percentage of participants
Placebo	Percentage of Participants Achieving Lp(a) <125 and <75 Nanomole/Liter (Nmol/L) at Days 60, 180	Lp(a) <75 nmol/L: Day 60	0.00 percentage of participants

Comparison: Lp(a) \<125 nmol/L: Day 60p-value: 0.00195% CI: [6.35, 1975.13]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 60p-value: <0.00195% CI: [142.74, 53463.34]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 60p-value: <0.00195% CI: [1700.95, 1523398.1]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 180p-value: 0.02695% CI: [1.48, 527.74]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 180p-value: <0.00195% CI: [17.99, 5320.81]Regression, Logistic

Comparison: Lp(a) \<125 nmol/L: Day 180p-value: <0.00195% CI: [166.84, 56127.55]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 60p-value: 0.02195% CI: [1.7, 635.94]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 60p-value: <0.00195% CI: [31.48, 10673.41]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 60p-value: <0.00195% CI: [646.35, 332498.98]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 180p-value: 0.07195% CI: [0.79, 321.21]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 180p-value: 0.00295% CI: [5.07, 1468.36]Regression, Logistic

Comparison: Lp(a) \<75 nmol/L: Day 180p-value: <0.00195% CI: [55.75, 16422.76]Regression, Logistic

Secondary

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

Population: Efficacy Analysis Set. Overall Number of Participants Analyzed = number of participants in each group. Number Analyzed = participants with available data at specified time points.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
16 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 540	1.4 percent change	Standard Error 3.55
16 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 60	-10.2 percent change	Standard Error 3.07
16 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 180	-7.0 percent change	Standard Error 3.49
16 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 240	-7.6 percent change	Standard Error 3.24
16 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 360	-2.9 percent change	Standard Error 3.56
96 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 60	-11.8 percent change	Standard Error 2.1
96 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 240	-13.8 percent change	Standard Error 2.11
96 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 360	-8.1 percent change	Standard Error 2.35
96 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 180	-9.6 percent change	Standard Error 2.37
96 mg LY3819469	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 540	-0.6 percent change	Standard Error 2.42
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 240	-14.0 percent change	Standard Error 1.98
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 360	-10.4 percent change	Standard Error 2.2
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 180	-12.6 percent change	Standard Error 1.68
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 60	-13.9 percent change	Standard Error 1.49
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 540	-9.1 percent change	Standard Error 2.13
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 540	-0.9 percent change	Standard Error 2.31
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 180	-12.6 percent change	Standard Error 1.68
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 60	-13.9 percent change	Standard Error 1.49
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 240	-9.0 percent change	Standard Error 2.05
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 360	-4.6 percent change	Standard Error 2.33
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 540	4.3 percent change	Standard Error 2.64
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 60	0.2 percent change	Standard Error 2.47
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 240	1.8 percent change	Standard Error 2.58
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 360	4.3 percent change	Standard Error 2.77
Placebo	Percent Change From Baseline in Apolipoprotein B (ApoB)	Baseline, Day 180	1.3 percent change	Standard Error 2.78

Comparison: Baseline to Day 60p-value: 0.0195% CI: [-17.5, -2.6]Mixed Models Analysis

Comparison: Baseline to Day 60p-value: <0.00195% CI: [-17.7, -5.8]Mixed Models Analysis

Comparison: Baseline to Day 60p-value: <0.00195% CI: [-19, -8.8]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: 0.06895% CI: [-16.2, 0.6]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: 0.00395% CI: [-17.1, -3.8]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: <0.00195% CI: [-19.3, -7.9]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: 0.02695% CI: [-16.7, -1.2]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-21.1, -9.3]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-21, -9.6]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-16.3, -4.4]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: 0.11195% CI: [-14.9, 1.7]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: <0.00195% CI: [-18.1, -5.3]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: <0.00195% CI: [-20, -7.8]Mixed Models Analysis

Comparison: 400 mg LY3819469, Placebop-value: 0.01395% CI: [-14.9, -1.9]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.5195% CI: [-10.7, 5.8]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.17395% CI: [-11.1, 2.1]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: <0.00195% CI: [-18.6, -6.8]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.13995% CI: [-11.2, 1.7]Mixed Models Analysis

Secondary

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

Population: Efficacy Analysis Set. Overall Number of Participants Analyzed = number of participants in each group. Number Analyzed = participants with available data at specified time points.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
16 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 60	-15.4 percent change	Standard Error 13.94
16 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 180	10.6 percent change	Standard Error 18.22
16 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 360	43.6 percent change	Standard Error 25.21
16 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 540	-7.7 percent change	Standard Error 14.93
16 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 240	-3.4 percent change	Standard Error 13.02
96 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 60	0.1 percent change	Standard Error 11.22
96 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 180	-6.5 percent change	Standard Error 10.59
96 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 540	-1.2 percent change	Standard Error 11.19
96 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 360	13.5 percent change	Standard Error 13.89
96 mg LY3819469	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 240	-8.4 percent change	Standard Error 8.6
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 540	0.9 percent change	Standard Error 11.12
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 60	-1.9 percent change	Standard Error 8
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 240	7.3 percent change	Standard Error 9.5
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 180	16.2 percent change	Standard Error 9.72
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 360	10.4 percent change	Standard Error 12.9
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 360	32.3 percent change	Standard Error 15.36
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 180	16.2 percent change	Standard Error 9.72
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 240	-1.2 percent change	Standard Error 8.67
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 60	-1.9 percent change	Standard Error 8
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 540	14.1 percent change	Standard Error 12.65
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 60	2.1 percent change	Standard Error 11.87
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 240	9.1 percent change	Standard Error 10.52
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 180	10.3 percent change	Standard Error 13.17
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 360	10.8 percent change	Standard Error 14.04
Placebo	Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Baseline, Day 540	0.1 percent change	Standard Error 11.89

Comparison: Baseline to Day 60p-value: 0.35395% CI: [-44.3, 23.3]Mixed Models Analysis

Comparison: Baseline to Day 60p-value: 0.90295% CI: [-28.7, 34.7]Mixed Models Analysis

Comparison: Baseline to Day 60p-value: 0.77995% CI: [-27.4, 27.1]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: 0.98795% CI: [-32.8, 49.7]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: 0.31695% CI: [-38.7, 17.2]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: 0.7295% CI: [-20.9, 40.4]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: 0.46195% CI: [-36.1, 22.6]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: 0.19495% CI: [-35.6, 9.4]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: 0.89895% CI: [-24, 27.2]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: 0.44895% CI: [-29.9, 17]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: 0.23395% CI: [-15.4, 98.4]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: 0.89195% CI: [-27.6, 44.9]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: 0.98495% CI: [-29, 39.9]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: 0.30295% CI: [-14.8, 67.5]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.68495% CI: [-37.9, 36.8]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.93395% CI: [-28.6, 36.3]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.96295% CI: [-26.7, 38.6]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.42295% CI: [-17.2, 56.9]Mixed Models Analysis

Secondary

Percent Change From Baseline in Lp(a)

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

Population: Efficacy Analysis Set. Overall Number of Participants Analyzed = number of participants in each group. Number Analyzed = participants with available data at specified time points.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
16 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 60	-46.2 percent change	Standard Error 6.04
16 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 540	-18.7 percent change	Standard Error 8.56
16 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 360	-30.8 percent change	Standard Error 9.19
16 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 180	-30.5 percent change	Standard Error 9.17
16 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 240	-47.7 percent change	Standard Error 6.63
96 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 540	-45.1 percent change	Standard Error 4.04
96 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 60	-80.4 percent change	Standard Error 1.53
96 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 240	-84.8 percent change	Standard Error 1.35
96 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 360	-67.7 percent change	Standard Error 2.99
96 mg LY3819469	Percent Change From Baseline in Lp(a)	Baseline, Day 180	-65.3 percent change	Standard Error 3.2
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Lp(a)	Baseline, Day 360	-91.1 percent change	Standard Error 0.69
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Lp(a)	Baseline, Day 540	-73.8 percent change	Standard Error 1.69
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Lp(a)	Baseline, Day 60	-95.4 percent change	Standard Error 0.26
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Lp(a)	Baseline, Day 180	-90.5 percent change	Standard Error 0.64
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Lp(a)	Baseline, Day 240	-96.8 percent change	Standard Error 0.23
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 60	-95.4 percent change	Standard Error 0.26
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 180	-90.5 percent change	Standard Error 0.64
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 240	-84.9 percent change	Standard Error 1.09
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 360	-68.1 percent change	Standard Error 2.46
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 540	-52.8 percent change	Standard Error 3.04
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 60	2.2 percent change	Standard Error 8.29
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 540	1.3 percent change	Standard Error 7.76
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 360	-0.9 percent change	Standard Error 9.53
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 240	-0.8 percent change	Standard Error 9.1
Placebo	Percent Change From Baseline in Lp(a)	Baseline, Day 180	2.2 percent change	Standard Error 9.78

Comparison: Baseline to Day 60p-value: <0.00195% CI: [-59.9, -30.9]Mixed Models Analysis

Comparison: Baseline to Day 60p-value: <0.00195% CI: [-84.7, -76.1]Mixed Models Analysis

Comparison: Baseline to Day 60p-value: <0.00195% CI: [-96.3, -94.5]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: 0.01995% CI: [-50.6, -6.2]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: <0.00195% CI: [-73.8, -55.9]Mixed Models Analysis

Comparison: Baseline to Day 180p-value: <0.00195% CI: [-92.6, -88.3]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-61.3, -28.3]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-88.1, -80.3]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-97.4, -95.9]Mixed Models Analysis

Comparison: Baseline to Day 240p-value: <0.00195% CI: [-87.9, -80.8]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: 0.02995% CI: [-49.4, -3.6]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: <0.00195% CI: [-74.9, -57.6]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: <0.00195% CI: [-92.9, -88.5]Mixed Models Analysis

Comparison: Baseline to Day 360p-value: <0.00195% CI: [-74.8, -59]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: 0.09395% CI: [-37.8, 3.7]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: <0.00195% CI: [-56, -33.2]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: <0.00195% CI: [-78.8, -68.5]Mixed Models Analysis

Comparison: Baseline to Day 540p-value: <0.00195% CI: [-61.7, -43.3]Mixed Models Analysis

Secondary

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

Population: Efficacy Analysis Set.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
16 mg LY3819469	Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360	-38.7 percent change	Standard Error 7.66
96 mg LY3819469	Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360	-77.4 percent change	Standard Error 1.97
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360	-95.0 percent change	Standard Error 0.45
Placebo	Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360	-76.7 percent change	Standard Error 2.06
Placebo	Percent Change From Baseline in Time Averaged Lp(a) Over Days 240-360	0.3 percent change	Standard Error 9.07

p-value: 0.00295% CI: [-54.9, -17.2]Mixed Models Analysis

p-value: <0.00195% CI: [-82.4, -71.1]Mixed Models Analysis

p-value: <0.00195% CI: [-96.1, -93.6]Mixed Models Analysis

p-value: <0.00195% CI: [-81.9, -70.2]Mixed Models Analysis

Secondary

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

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
16 mg LY3819469	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3819469	1853 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 36
96 mg LY3819469	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3819469	10110 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 26
400 mg LY3819469 and 400 mg LY3819469 + Placebo (400 mg LY3819469 Pooled)	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3819469	55242 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 42
Placebo	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3819469	46633 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 13

Source: ClinicalTrials.gov · Data processed: Sep 2, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

Percent Change From Baseline in Apolipoprotein B (ApoB)

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

Percent Change From Baseline in Lp(a)

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

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