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)

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 Overview

• Status: Completed
• Conditions: Lipoprotein Disorder
• Intervention / Treatment: Drug: Placebo; Drug: LY3819469

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1407
    • CEMEDIC
  • Córdoba, Argentina, 5000
    • Hospital San Roque
  • Salta, Argentina, 4406
    • Centro Cardiovascular Salta
  • Santa Fe, Argentina, 3000
    • Centro de Investigaciones Clinicas del Litoral
  • Buenos Air
    • Ciudad Autónoma de Buenos Aire, Buenos Air, Argentina, C1027AAP
      • Centro de Investigaciones Metabólicas (CINME)
  • Ciudad Aut
    • Buenos Aires, Ciudad Aut, Argentina, C1430CKE
      • Glenny Corp. S.A.
  • Ciudad Autónoma De Buenos Aire
    • Balvanera, Ciudad Autónoma De Buenos Aire, Argentina, C1056ABH
      • Investigaciones Medicas IMOBA SRL
    • Buenos Aires, Ciudad Autónoma De Buenos Aire, Argentina, C1061AAS
      • CIPREC
  • Ciudad Autónoma De Buenos Aires
    • Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina, C1128AAF
      • Mautalen Salud e Investigacion
  • Tucumán
    • San Miguel de Tucuman, Tucumán, Argentina, 4000
      • Investigaciones Clinicas Tucuman
    • San Miguel de Tucuman, Tucumán, Argentina, 4000
      • Centro Modelo de Cardiología
• China
  • Hainan
    • Sanya, Hainan, China, 572000
      • Third People's Hospital of Hainan Province
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330009
      • The Third Hospital of Nanchang
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
• Denmark
  • Hovedstaden
    • Herlev, Hovedstaden, Denmark, 2730
      • Sanos Clinic
  • Nordjylland
    • Gandrup, Nordjylland, Denmark, 9362
      • Sanos Clinic - Nordjylland
  • Syddanmark
    • Vejle, Syddanmark, Denmark, 7100
      • Sanos Clinic - Syddanmark
• Germany
  • Berlin, Germany, 10559
    • Kardiologische Praxen im Spreebogen
  • Hamburg, Germany, 22607
    • Diabeteszentrum Hamburg West
  • Hamburg, Germany, 22041
    • Cardiologicum Hamburg
  • Berlin
    • Spandau, Berlin, Germany, 13597
      • Medizinisches Versorgungszentrum am Bahnhof Spandau
  • Hessen
    • Bad Homburg, Hessen, Germany, 61348
      • Kardiologische Praxis Dr. med. univ. Wolfgang Jungmair
    • Frankfurt, Hessen, Germany, 60389
      • Cardioangiologisches Centrum Bethanien
  • Nordrhein-Westfalen
    • Bielefeld, Nordrhein-Westfalen, Germany, 33604
      • Klinikum Bielefeld Mitte
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
      • SMO.MD GmbH
• Japan
  • Miyazaki, Japan, 880-2102
    • Miyazaki Medical Association Hospital
  • Osaka, Japan, 530-0001
    • AMC Nishiumeda Clinic
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8543
      • Sapporo Medical University Hospital
  • Hyogo
    • Nishinomiya, Hyogo, Japan, 663-8501
      • Hyogo Medical University Hospital
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0375
      • Kitasato University Hospital
  • Osaka
    • Izumisano, Osaka, Japan, 598-8577
      • Rinku General Medical Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 103-0027
      • Tokyo-Eki Center-building Clinic
    • Shinjuku-ku, Tokyo, Japan, 160-0008
      • Heishinkai Medical Group ToCROM Clinic
    • Shinjuku-ku, Tokyo, Japan, 160-0004
      • Clinical Research Hospital Tokyo
• Mexico
  • Aguascalientes, Mexico, 20230
    • Fundación Cardiovascular de Aguascalientes A.C.
  • Querétaro, Mexico, 76000
    • Centro de Estudios Clínicos de Querétaro (CECLIQ)
  • Baja California
    • Tijuana, Baja California, Mexico, 22500
      • Centro de Investigacion Cardiovascular y Metabolica
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Virgen Cardiovascular Research SC
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80230
      • Centro para el Desarrollo de la Medicina y de Asistencia Médica Especializada S.C.
• Netherlands
  • Sneek, Netherlands, 8601 ZR
    • Antonius Ziekenhuis, locatie D&A Research and Genetics
  • Noord-Brabant
    • Breda, Noord-Brabant, Netherlands, 4818 CK
      • Amphia Ziekenhuis, locatie Breda Molengracht
  • Overijssel
    • Enschede, Overijssel, Netherlands, 7512 KZ
      • Medisch Spectrum Twente
    • Hardenberg, Overijssel, Netherlands, 7772 SE
      • Saxenburgh Medisch Centrum
  • Zuid-Holla
    • Delft, Zuid-Holla, Netherlands, 2625 AD
      • Reinier de Graaf Ziekenhuis, locatie Delft
  • Zuid-Holland
    • Gouda, Zuid-Holland, Netherlands, 2803HH
      • Groene Hart Ziekenhuis
• Romania
  • Iași, Romania, 700687
    • Cardiomed Iași
  • Argeș
    • Pitești, Argeș, Romania, 110437
      • Sal Med Srl
  • Brașov
    • Brasov, Brașov, Romania, 500283
      • C.M.D.T.A. Neomed
  • București
    • Bucharest, București, Romania, 011053
      • Hightech Medical Services SRL-Centrul pentru Studiul Metabolismului
    • Bucharest, București, Romania, 50538
      • Centrul Medical Endocrinologie si Diabet Dr. Paveliu
  • Maramureș
    • Baia Mare, Maramureș, Romania, 430123
      • Private Practice - Dr. Mercea Corina Delia
  • Mureș
    • Târgu Mureș, Mureș, Romania, 540124
      • Cardiomed
    • Târgu-Mureș, Mureș, Romania, 540143
      • Private Practice - Dr. Cristian Podoleanu
  • Timiș
    • Timisoara, Timiș, Romania, 300462
      • Centrul Medical Medicalis
• Spain
  • Granada, Spain, 18014
    • Hospital Unviersitario Virgen Nieves
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Andalucía
    • Cordoba, Andalucía, Spain, 14004
      • Hospital Universitario Reina Sofia
  • Barcelona [Barcelona]
    • Badalona, Barcelona [Barcelona], Spain, 08916
      • Hospital Germans Trias i Pujol
  • Catalunya [Cataluña]
    • L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain, 08907
      • Hospital Universitari de Bellvitge
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Care Access - 801 South Power Road, Mesa
  • California
    • Pasadena, California, United States, 91105
      • Care Access - South Pasadena
    • Santa Clarita, California, United States, 91321
      • Care Access - Santa Clarita
  • Florida
    • Spring Hill, Florida, United States, 34609
      • Care Access - Spring Hill
    • Sun City, Florida, United States, 33573
      • Care Access - Pebble Beach Boulevard, Tampa
    • Tamarac, Florida, United States, 33321
      • Care Access - Tamarac
    • Tampa, Florida, United States, 33625
      • Care Access - Tampa
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Care Access - Lake Charles
  • Maryland
    • Baltimore, Maryland, United States, 21213
      • Care Access - Baltimore
  • Massachusetts
    • Dorchester, Massachusetts, United States, 02124
      • Care Access - Dorchester
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
    • Lima, Ohio, United States, 45805
      • Care Access - Lima
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Research, LLC
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Yardley, Pennsylvania, United States, 19067
      • Cardiology Consultants of Philadelphia Yardley
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Care Access - Rapid City
  • Texas
    • Georgetown, Texas, United States, 78633
      • Care Access - Georgetown
    • Katy, Texas, United States, 77450
      • Care Access - Katy
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Virginia Heart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 16 mg LY3819469; Participants received 16 milligrams (mg) of LY3819469 on day 1 and day 180, administered as a subcutaneous (SC) injection.	Drug: LY3819469; Administered SC
Experimental: 96 mg LY3819469; Participants received 96 mg of LY3819469 on day 1 and day 180, administered as a SC injection.	Drug: LY3819469; Administered SC
Experimental: 400 mg LY3819469; Participants received 400 mg of LY3819469 on day 1 and day 180, administered as a SC injection.	Drug: LY3819469; Administered SC
Experimental: 400 mg LY3819469 + Placebo; Participants received 400 mg of LY3819469 on day 1 and placebo on day 180, administered as a SC injection.	Drug: Placebo; Administered SC; Drug: LY3819469; Administered SC
Placebo Comparator: Placebo; Participants received placebo on day 1 and day 180, administered as a SC injection.	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Days 60 - 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Days 240, 360, and 540
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.	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.	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.	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.	Day 1: 0.5 hours, 4-9 hours post-dose; Day 180: 24-36 hours post-dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Actual): October 23, 2023
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 18547; J3L-MC-EZEB (Other Identifier: Eli Lilly and Company); 2022-501426-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No