A Study of LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events

NCT05563246 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 18495J2O-MC-EKBC2022-501466-21-00
• Study Type: interventional
• Target: 233
• Locations: 8 countries
• Sites: 42

Brief Summary

The main purpose of this study is to evaluate the efficacy and safety of LY3473329 in adult participants with elevated Lp(a) at high risk for cardiovascular events.

Conditions

Lipoprotein Disorder

Keywords

Atherosclerotic cardiovascular disease; ASCVD; Dyslipidemia; Lipoprotein(a); Lp(a); Cardiovascular; Cardiovascular disease; Cholesterol; Hyperlipidemia

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Lp(a) - Assessed Via Intact Lp(a) Assay

  Least Squares Mean (LS Mean) was calculated using a Mixed Model for Repeated Measures (MMRM): Log (Actual Measurement/Baseline) = Log (Baseline) + Country + Treatment + Time + Treatment\*Time.

  Baseline, Week 12

• Percent Change From Baseline in Lp(a) - Assessed Via Apo(a) Assay

  LS Mean was calculated using a MMRM: Log (Actual Measurement/Baseline) = Log (Baseline) + Country + Treatment + Time + Treatment\*Time.

  Baseline, Week 12

Secondary Outcomes (5)

• Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Intact Lp(a) Assay

  Week 12

• Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Apo(a) Assay

  Week 12

• Percent Change From Baseline in Apolipoprotein B (ApoB)

  Baseline, Week 12

• Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)

  Baseline, Week 12

• Pharmacokinetics (PK): Trough Concentrations (C-trough) of LY3473329

  Week from randomization 1, 2, 8, 12: Pre-dose

Study Arms (4)

10 mg LY3473329

EXPERIMENTAL

Participants received 10 milligrams (mg) of LY3473329 administered orally once daily (QD) over a 12-week treatment period.

Drug: LY3473329

60 mg LY3473329

EXPERIMENTAL

Participants received 60 mg of LY3473329 administered orally QD over a 12-week treatment period.

Drug: LY3473329

240 mg LY3473329

EXPERIMENTAL

Participants received 240 mg of LY3473329 administered orally QD over a 12-week treatment period.

Drug: LY3473329

Placebo

PLACEBO COMPARATOR

Participants received a matching dose of placebo administered orally QD over a 12-week treatment period.

Drug: Placebo

Interventions

LY3473329 DRUG

Administered orally

10 mg LY3473329; 240 mg LY3473329; 60 mg LY3473329

Placebo DRUG

Administered orally

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
• Participants with Lp(a) ≥175 nmol/L at randomization, measured at the central laboratory.
• High risk for cardiovascular events defined as documented coronary artery disease (CAD), stroke, or peripheral artery disease or atherosclerotic cardiovascular disease (ASCVD) risk equivalents (familial hypercholesterolemia or type 2 diabetes).
• Participants on the following medications according to local practice must be on a stable regimen for at least 4 weeks prior to randomization and expected to remain on a stable regimen through the end of the post-treatment follow-up 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.
• Males who agree to use highly effective or effective methods of contraception may participate in this trial.
• Women of childbearing potential (WOCBP) who agree to use highly effective or effective methods of contraception and 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 (42)

Care Access - Baltimore

Baltimore, Maryland, 21213, United States

Location

Care Access - Dorchester

Dorchester, Massachusetts, 02124, United States

Location

Care Access - Lima

Lima, Ohio, 45805, United States

Location

Core Research Group

Brisbane, Queensland, 4064, Australia

Location

Nightingale Research

Adelaide, South Australia, 5000, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Victorian Heart Hospital

Clayton, Victoria, 3168, Australia

Location

CEDOES

Vitória, Espírito Santo, 29055450, Brazil

Location

Pesquisa Clínica em Diabetes - Dra Rosângela Réa

Curitiba, Paraná, 80040-110, Brazil

Location

Centro de Pesquisa Clinica do Coracao

Acaraju, Sergipe, 49055-530, Brazil

Location

Incor - Instituto do Coracao

São Paulo, São Paulo, 05403-900, Brazil

Location

IBPClin - Instituto Brasil de Pesquisa Clínica

Rio de Janeiro, 22241-180, Brazil

Location

CPCLIN

São Paulo, 01228-200, Brazil

Location

Instituto Dante Pazzanese de Cardiology

São Paulo, 04012-909, Brazil

Location

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, 04266-010, Brazil

Location

Third People's Hospital of Hainan Province

Sanya, Hainan, 572000, China

Location

The First Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

The Fourth Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Changzhou Second People's Hospital

Changzhou, Jiangsu, 213000, 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

China-Japan Union Hospital

Changchun, Jilin, 130033, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Gemeinschaftpraxis Dr. med. Martin Prohaska und Dr. med. Felix Schulte

Mühldorf, Bavaria, 84453, Germany

Location

ClinPhenomics GmbH & Co KG

Frankfurt am Main, Hesse, 60596, Germany

Location

Kath. St.-Johannes-Gesellschaft Dortmund

Dortmund, North Rhine-Westphalia, 44137, Germany

Location

Private Practice - Dr. Frank Menzel

Dessau, 06846, Germany

Location

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, Csongrád megye, 6720, Hungary

Location

Medifarma 98 Kft

Nyíregyháza, Nyíregyháza, 4400, Hungary

Location

Flor Ferenc Hospital of Pest County

Kistarcsa, Pest County, 2143, Hungary

Location

Belvárosi Egészségház

Zalaegerszeg, Zala County, 8900, Hungary

Location

Dél-Pesti Centrumkórház

Budapest, 1097, Hungary

Location

Semmelweis University

Budapest, 1122, Hungary

Location

Funabashi Municipal Medical Center

Funabashi, Chiba, 273-0853, Japan

Location

Kokura Memorial Hospital

Kitakyushu, Fukuoka, 802-8555, Japan

Location

Iwate Prefectural Central Hospital

Morioka, Iwate, 020-0066, Japan

Location

Medical Corporation Heishinkai OCROM Clinic

Suita-shi, Osaka, 565-0853, Japan

Location

Minamino Cardiovascular Hospital

Hachiōji, Tokyo, 192-0918, Japan

Location

Hiroshima City Hospital

Hiroshima, 730-8518, Japan

Location

Miyazaki Medical Association Hospital

Miyazaki, 880-2102, Japan

Location

VieCuri Medisch Centrum, locatie Venlo

Venlo, Limburg, 5912 BL, Netherlands

Location

Meander Medisch Centrum

Amersfoort, Utrecht, 3813 TZ, Netherlands

Location

Related Publications (3)

• Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, Haupt A, Krege JH. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2025 Jan 21;333(3):222-231. doi: 10.1001/jama.2024.24017.

  PMID: 39556768 DERIVED

• Nicholls SJ, Nelson AJ, Michael LF. Oral agents for lowering lipoprotein(a). Curr Opin Lipidol. 2024 Dec 1;35(6):275-280. doi: 10.1097/MOL.0000000000000953. Epub 2024 Sep 25.

  PMID: 39329200 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 LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events (KRAKEN)

MeSH Terms

Conditions

Atherosclerosis; Dyslipidemias; Cardiovascular Diseases; Hyperlipidemias

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Due to country-specific restrictions on sample storage, measurements for the primary endpoint and key secondary endpoints involving Lp(a), as assessed by the intact Lp(a) assay, could not be obtained from participants at the Chinese sites. As a result, intact Lp(a) assay outcome data from these sites were not reported.

Results Point of Contact

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

ClinicalTrials.gov@lilly.com

800-545-5979

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: September 28, 2022
• First Posted: October 3, 2022
• Study Start: November 24, 2022
• Primary Completion: March 14, 2024
• Study Completion: March 14, 2024
• Last Updated: March 25, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-03

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

DE (4); HU (6); CN (8); JP (7); NL (2); AU (4); BR (8); US (3)