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

NCT05565742 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 18547J3L-MC-EZEB2022-501426-38-00
• Study Type: interventional
• Target: 320
• Locations: 10 countries
• Sites: 80

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.

Conditions

Lipoprotein Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

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

  Baseline, Days 240 - 360

• 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 240, 360, and 540

  Days 240, 360, and 540

• Percent Change From Baseline in Lp(a)

  Baseline, Days 60, 180, 240, 360, and 540

• Percent Change From Baseline in Apolipoprotein B (ApoB)

  Baseline, Days 60, 180, 240, 360, and 540

Study Arms (5)

16 mg LY3819469

EXPERIMENTAL

Participants received 16 milligrams (mg) of LY3819469 on day 1 and day 180, administered as a subcutaneous (SC) injection.

Drug: LY3819469

96 mg LY3819469

EXPERIMENTAL

Participants received 96 mg of LY3819469 on day 1 and day 180, administered as a SC injection.

Drug: LY3819469

400 mg LY3819469

EXPERIMENTAL

Participants received 400 mg of LY3819469 on day 1 and day 180, administered as a SC injection.

Drug: LY3819469

400 mg LY3819469 + Placebo

EXPERIMENTAL

Participants received 400 mg of LY3819469 on day 1 and placebo on day 180, administered as a SC injection.

Drug: LY3819469; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants received placebo on day 1 and day 180, administered as a SC injection.

Drug: Placebo

Interventions

LY3819469 DRUG

Administered SC

16 mg LY3819469; 400 mg LY3819469; 400 mg LY3819469 + Placebo; 96 mg LY3819469

Placebo DRUG

Administered SC

400 mg LY3819469 + Placebo; Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (80)

Care Access - 801 South Power Road, Mesa

Mesa, Arizona, 85206, United States

Location

Care Access - South Pasadena

Pasadena, California, 91105, United States

Location

Care Access - Santa Clarita

Santa Clarita, California, 91321, United States

Location

Care Access - Spring Hill

Spring Hill, Florida, 34609, United States

Location

Care Access - Pebble Beach Boulevard, Tampa

Sun City, Florida, 33573, United States

Location

Care Access - Tamarac

Tamarac, Florida, 33321, United States

Location

Care Access - Tampa

Tampa, Florida, 33625, United States

Location

Care Access - Lake Charles

Lake Charles, Louisiana, 70601, United States

Location

Care Access - Baltimore

Baltimore, Maryland, 21213, United States

Location

Care Access - Dorchester

Dorchester, Massachusetts, 02124, United States

Location

Aventiv Research Inc

Columbus, Ohio, 43213, United States

Location

Care Access - Lima

Lima, Ohio, 45805, United States

Location

Capital Area Research, LLC

Camp Hill, Pennsylvania, 17011, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17602, United States

Location

Cardiology Consultants of Philadelphia Yardley

Yardley, Pennsylvania, 19067, United States

Location

Care Access - Rapid City

Rapid City, South Dakota, 57701, United States

Location

Care Access - Georgetown

Georgetown, Texas, 78633, United States

Location

Care Access - Katy

Katy, Texas, 77450, United States

Location

Virginia Heart

Falls Church, Virginia, 22042, United States

Location

Mautalen Salud e Investigación

Buenos Aires, Buenos Aires F.D., C1128AAF, Argentina

Location

Centro de Investigaciones Metabólicas (CINME)

Ciudad Autónoma de Buenos Aire, Buenos Air, C1027AAP, Argentina

Location

Glenny Corp. S.A.

Buenos Aires, Ciudad Aut, C1430CKE, Argentina

Location

Investigaciones Medicas Imoba Srl

Balvanera, Ciudad Autónoma de Buenos Aire, C1056ABH, Argentina

Location

CIPREC

Buenos Aires, Ciudad Autónoma de Buenos Aire, C1061AAS, Argentina

Location

Centro Modelo de Cardiología

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Investigaciones Clínicas Tucumán

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

CEMEDIC

Buenos Aires, 1407, Argentina

Location

Hospital San Roque

Córdoba, 5000, Argentina

Location

Centro Cardiovascular Salta

Salta, 4406, Argentina

Location

Centro de Investigaciones Clinicas del Litoral

Santa Fe, 3000, Argentina

Location

Third People's Hospital of Hainan Province

Sanya, Hainan, 572000, China

Location

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

Location

The Third Hospital of Nanchang

Nanchang, Jiangxi, 330009, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Sanos Clinic

Herlev, Capital Region, 2730, Denmark

Location

Sanos Clinic - Nordjylland

Gandrup, North Denmark, 9362, Denmark

Location

Sanos Clinic - Syddanmark

Vejle, Region Syddanmark, 7100, Denmark

Location

Kardiologische Praxis Dr. med. univ. Wolfgang Jungmair

Bad Homburg, Hesse, 61348, Germany

Location

Cardioangiologisches Centrum Bethanien

Frankfurt am Main, Hesse, 60389, Germany

Location

Klinikum Bielefeld Mitte

Bielefeld, North Rhine-Westphalia, 33604, Germany

Location

SMO.MD GmbH

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Medizinisches Versorgungszentrum am Bahnhof Spandau

Spandau, State of Berlin, 13597, Germany

Location

Kardiologische Praxen im Spreebogen

Berlin, 10559, Germany

Location

Cardiologicum Hamburg

Hamburg, 22041, Germany

Location

Diabeteszentrum Hamburg West

Hamburg, 22607, Germany

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Hyogo Medical University Hospital

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Kitasato University Hospital

Sagamihara, Kanagawa, 252-0375, Japan

Location

Rinku General Medical Center

Izumisano, Osaka, 598-8577, Japan

Location

Tokyo-Eki Center-building Clinic

Chuo-ku, Tokyo, 103-0027, Japan

Location

Clinical Research Hospital Tokyo

Shinjuku-ku, Tokyo, 160-0004, Japan

Location

Heishinkai Medical Group ToCROM Clinic

Shinjuku-ku, Tokyo, 160-0008, Japan

Location

Miyazaki Medical Association Hospital

Miyazaki, 880-2102, Japan

Location

AMC Nishiumeda Clinic

Osaka, 530-0001, Japan

Location

Centro de Investigacion Cardiovascular y Metabólica

Tijuana, Estado de Baja California, 22500, Mexico

Location

Virgen Cardiovascular Research SC

Guadalajara, Jalisco, 44670, Mexico

Location

Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.

Culiacán, Sinaloa, 80230, Mexico

Location

Fundación Cardiovascular de Aguascalientes A.C.

Aguascalientes, 20230, Mexico

Location

Centro de Estudios Clínicos de Querétaro (CECLIQ)

Querétaro, 76000, Mexico

Location

Amphia Ziekenhuis, locatie Breda Molengracht

Breda, North Brabant, 4818 CK, Netherlands

Location

Medisch Spectrum Twente

Enschede, Overijssel, 7512 KZ, Netherlands

Location

Saxenburgh Medisch Centrum

Hardenberg, Overijssel, 7772 SE, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, South Holland, 2803HH, Netherlands

Location

Reinier de Graaf Ziekenhuis, locatie Delft

Delft, Zuid-Holla, 2625 AD, Netherlands

Location

Antonius Ziekenhuis, locatie D&A Research and Genetics

Sneek, 8601 ZR, Netherlands

Location

Sal Med Srl

Piteşti, Argeş, 110437, Romania

Location

C.M.D.T.A. Neomed

Brasov, Brașov County, 500283, Romania

Location

Hightech Medical Services SRL-Centrul pentru Studiul Metabolismului

Bucharest, București, 011053, Romania

Location

Centrul Medical Endocrinologie si Diabet Dr. Paveliu

Bucharest, București, 50538, Romania

Location

Private Practice - Dr. Mercea Corina Delia

Baia Mare, Maramureş, 430123, Romania

Location

Cardiomed

Târgu Mureş, Mureș County, 540124, Romania

Location

Private Practice - Dr. Cristian Podoleanu

Târgu Mureş, Mureș County, 540143, Romania

Location

Centrul Medical Medicalis

Timișoara, Timiș County, 300462, Romania

Location

Cardiomed Iași

Iași, 700687, Romania

Location

Hospital Universitario Reina Sofia

Córdoba, Andalusia, 14004, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona [Barcelona], 08916, Spain

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Catalunya [Cataluña], 08907, Spain

Location

Hospital Unviersitario Virgen Nieves

Granada, 18014, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (3)

• Nissen SE, Ni W, Shen X, Wang Q, Navar AM, Nicholls SJ, Wolski K, Michael L, Haupt A, Krege JH; ALPACA Trial Investigators. Lepodisiran - A Long-Duration Small Interfering RNA Targeting Lipoprotein(a). N Engl J Med. 2025 May 1;392(17):1673-1683. doi: 10.1056/NEJMoa2415818. Epub 2025 Mar 30.

  PMID: 40162643 DERIVED

• Makhmudova U, Steinhagen-Thiessen E, Volpe M, Landmesser U. Advances in nucleic acid-targeted therapies for cardiovascular disease prevention. Cardiovasc Res. 2024 Sep 2;120(10):1107-1125. doi: 10.1093/cvr/cvae136.

  PMID: 38970537 DERIVED

• Karp A, Jacobs M, Barris B, Labkowsky A, Frishman WH. Lipoprotein(a): A Review of Risk Factors, Measurements, and Novel Treatment Modalities. Cardiol Rev. 2025 Jul-Aug 01;33(4):352-358. doi: 10.1097/CRD.0000000000000667. Epub 2024 Feb 28.

  PMID: 38415744 DERIVED

Related Links

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

08005455979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 4, 2022
• Study Start: October 20, 2022
• Primary Completion: October 23, 2023
• Study Completion: October 17, 2024
• Last Updated: May 28, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

NL (6); DE (8); RO (9); JP (9); ES (6); AR (11); ME (5); CN (4); US (19); DK (3)