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

KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Once-Daily LY3473329 in Adults With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events

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.

Study Overview

• Status: Completed
• Conditions: Lipoprotein Disorder
• Intervention / Treatment: Drug: Placebo; Drug: LY3473329

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4064
      • Core Research Group
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Adelaide, South Australia, Australia, 5000
      • Nightingale Research
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Victorian Heart Hospital
• Brazil
  • Rio de Janeiro, Brazil, 22241-180
    • IBPClin - Instituto Brasil de Pesquisa Clínica
  • Sao Paulo, Brazil, 01228-200
    • CPCLIN
  • São Paulo, Brazil, 04266-010
    • CEPIC - Centro Paulista de Investigacao Clinica
  • São Paulo, Brazil, 04012-909
    • Instituto Dante Pazzanese de Cardiology
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055450
      • CEDOES
  • Paraná
    • Curitiba, Paraná, Brazil, 80040-110
      • Pesquisa Clínica em Diabetes - Dra Rosângela Réa
  • Sergipe
    • Acaraju, Sergipe, Brazil, 49055-530
      • Centro de Pesquisa Clinica do Coracao
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 05403-900
      • Incor - Instituto do Coracao
• China
  • Hainan
    • Sanya, Hainan, China, 572000
      • Third People's Hospital of Hainan Province
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The First Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Hospital of Harbin Medical University
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Second People's Hospital
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330009
      • The Third Hospital of Nanchang
  • Jilin
    • Changchun, Jilin, China, 130033
      • China-Japan Union Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital Of Xi'an Jiaotong University
• Germany
  • Dessau, Germany, 06846
    • Private Practice - Dr. Frank Menzel
  • Bayern
    • Mühldorf, Bayern, Germany, 84453
      • Gemeinschaftpraxis Dr. med. Martin Prohaska und Dr. med. Felix Schulte
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • ClinPhenomics GmbH & Co KG
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44137
      • Kath. St.-Johannes-Gesellschaft Dortmund
• Hungary
  • Budapest, Hungary, 1122
    • Semmelweis University
  • Budapest, Hungary, 1097
    • Dél-Pesti Centrumkórház
  • Csongrád
    • Szeged, Csongrád, Hungary, 6720
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Nyíregyháza
    • Nyiregyhaza, Nyíregyháza, Hungary, 4400
      • Medifarma 98 Kft
  • Pest
    • Kistarcsa, Pest, Hungary, 2143
      • Flor Ferenc Hospital of Pest County
  • Zala
    • Zalaegerszeg, Zala, Hungary, 8900
      • Belvárosi Egészségház
• Japan
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hospital
  • Miyazaki, Japan, 880-2102
    • Miyazaki Medical Association Hospital
  • Chiba
    • Funabashi, Chiba, Japan, 273-0853
      • Funabashi Municipal Medical Center
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-0066
      • Iwate Prefectural Central Hospital
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0853
      • Medical Corporation Heishinkai OCROM Clinic
  • Tokyo
    • Hachioji, Tokyo, Japan, 192-0918
      • Minamino Cardiovascular Hospital
• Netherlands
  • Limburg
    • Venlo, Limburg, Netherlands, 5912 BL
      • VieCuri Medisch Centrum, locatie Venlo
  • Utrecht
    • Amersfoort, Utrecht, Netherlands, 3813 TZ
      • Meander Medisch Centrum
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21213
      • Care Access - Baltimore
  • Massachusetts
    • Dorchester, Massachusetts, United States, 02124
      • Care Access - Dorchester
  • Ohio
    • Lima, Ohio, United States, 45805
      • Care Access - Lima

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
• 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.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg LY3473329; Participants received 10 milligrams (mg) of LY3473329 administered orally once daily (QD) over a 12-week treatment period.	Drug: LY3473329; Administered orally
Experimental: 60 mg LY3473329; Participants received 60 mg of LY3473329 administered orally QD over a 12-week treatment period.	Drug: LY3473329; Administered orally
Experimental: 240 mg LY3473329; Participants received 240 mg of LY3473329 administered orally QD over a 12-week treatment period.	Drug: LY3473329; Administered orally
Placebo Comparator: Placebo; Participants received a matching dose of placebo administered orally QD over a 12-week treatment period.	Drug: Placebo; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Intact Lp(a) Assay	The percentage of participants who achieved Lp(a) less than (<) 125 nmol/L, as measured using the intact Lp(a) assay, with data analysis performed through a logistic regression model that included imputed missing values, was reported.	Week 12
Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Apo(a) Assay	The percentage of participants who achieved Lp(a) < 125 nmol/L, as measured using the apo(a) assay, with data analysis performed through a logistic regression model that included imputed missing values, was reported.	Week 12
Percent Change From Baseline in Apolipoprotein B (ApoB)	LS Mean was calculated using a MMRM: Log (Actual Measurement/Baseline) = Log (Baseline) + Country + Baseline Lp(a) Stratum + Treatment + Time + Treatment*Time.	Baseline, Week 12
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)	LS Mean was calculated using a MMRM: Log (Actual Measurement/Baseline) = Log (Baseline) + Country + Baseline Lp(a) Stratum + Treatment + Time + Treatment*Time.	Baseline, Week 12
Pharmacokinetics (PK): Trough Concentrations (C-trough) of LY3473329	C-trough were measured at specified time points to assess the minimum concentration of LY3473329 in the blood before the next dose was administered.	Week from randomization 1, 2, 8, 12: Pre-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 LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events (KRAKEN)

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2022
• Primary Completion (Actual): March 14, 2024
• Study Completion (Actual): March 14, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Cholesterol; Dyslipidemia; Lipoprotein(a); Cardiovascular; Hyperlipidemia; Atherosclerotic cardiovascular disease; ASCVD; Lp(a)
• Other Study ID Numbers: 18495; J2O-MC-EKBC (Other Identifier: Eli Lilly and Company); 2022-501466-21-00 (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