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

Phase 2

Completed

Conditions: Lipoprotein Disorder

Interventions: Drug: LY3819469
Drug: Placebo

Registration Number: NCT05565742

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 320

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
16 mg LY3819469	LY3819469	Participants received 16 milligrams (mg) of LY3819469 on day 1 and day 180, administered as a subcutaneous (SC) injection.
96 mg LY3819469	LY3819469	Participants received 96 mg of LY3819469 on day 1 and day 180, administered as a SC injection.
400 mg LY3819469	LY3819469	Participants received 400 mg of LY3819469 on day 1 and day 180, administered as a SC injection.
400 mg LY3819469 + Placebo	LY3819469	Participants received 400 mg of LY3819469 on day 1 and placebo on day 180, administered as a SC injection.
400 mg LY3819469 + Placebo	Placebo	Participants received 400 mg of LY3819469 on day 1 and placebo on day 180, administered as a SC injection.
Placebo	Placebo	Participants received placebo on day 1 and day 180, administered as a SC injection.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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.
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.

Trial Locations

Locations (80): Glenny Corp. S.A.
🇦🇷
Buenos Aires, Ciudad Aut, Argentina
Hyogo Medical University Hospital
🇯🇵
Nishinomiya, Hyogo, Japan
Care Access - 801 South Power Road, Mesa
🇺🇸
Mesa, Arizona, United States
Care Access - South Pasadena
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Pasadena, California, United States
Care Access - Santa Clarita
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Santa Clarita, California, United States
Care Access - Spring Hill
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Spring Hill, Florida, United States
Care Access - Pebble Beach Boulevard, Tampa
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Sun City, Florida, United States
Care Access - Tamarac
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Tamarac, Florida, United States
Care Access - Tampa
🇺🇸
Tampa, Florida, United States
Care Access - Lake Charles
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Lake Charles, Louisiana, United States
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Glenny Corp. S.A.
🇦🇷Buenos Aires, Ciudad Aut, Argentina