Lipoprotein DisorderPhase 2KRAKENNCT05563246
A Study of LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events
A Phase 2 study testing LY3473329 in people with Lipoprotein Disorder, run by Eli Lilly and Company at 42 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Lipoprotein Disorder
- What is being tested?
- LY3473329
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 233 participants
- Where
- 42 sitesin 8 countries
- Study dates
- 24 Nov 2022to 14 Mar 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- acute limb ischemia
- Have, in the 6 months prior to day 1, uncontrolled Type 1 or Type 2 diabetes
- Have uncontrolled hypertension
Trial locations and contacts
42 sites in 8 countries.
42 sites in 8 countries
Brazil8 sites
Centro de Pesquisa Clinica do Coracao
Acaraju, Sergipe, 49055-530
Pesquisa Clínica em Diabetes - Dra Rosângela Réa
Curitiba, Paraná, 80040-110
IBPClin - Instituto Brasil de Pesquisa Clínica
Rio de Janeiro, 22241-180
Incor - Instituto do Coracao
São Paulo, São Paulo, 05403-900
CPCLIN
São Paulo, 01228-200
Instituto Dante Pazzanese de Cardiology
São Paulo, 04012-909
CEPIC - Centro Paulista de Investigação Clínica
São Paulo, 04266-010
CEDOES
Vitória, Espírito Santo, 29055450
China8 sites
China-Japan Union Hospital
Changchun, Jilin, 130033
Changzhou Second People's Hospital
Changzhou, Jiangsu, 213000
The First Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
The Fourth Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
The Third Hospital of Nanchang
Nanchang, Jiangxi, 330009
The Second Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210011
Third People's Hospital of Hainan Province
Sanya, Hainan, 572000
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061
Japan7 sites
Funabashi Municipal Medical Center
Funabashi, Chiba, 273-0853
Minamino Cardiovascular Hospital
Hachiōji, Tokyo, 192-0918
Hiroshima City Hospital
Hiroshima, 730-8518
Kokura Memorial Hospital
Kitakyushu, Fukuoka, 802-8555
Miyazaki Medical Association Hospital
Miyazaki, 880-2102
Iwate Prefectural Central Hospital
Morioka, Iwate, 020-0066
Medical Corporation Heishinkai OCROM Clinic
Suita-shi, Osaka, 565-0853
Hungary6 sites
Dél-Pesti Centrumkórház
Budapest, 1097
Semmelweis University
Budapest, 1122
Flor Ferenc Hospital of Pest County
Kistarcsa, Pest County, 2143
Medifarma 98 Kft
Nyíregyháza, Nyíregyháza, 4400
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
Szeged, Csongrád megye, 6720
Belvárosi Egészségház
Zalaegerszeg, Zala County, 8900
Australia4 sites
Nightingale Research
Adelaide, South Australia, 5000
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Core Research Group
Brisbane, Queensland, 4064
Victorian Heart Hospital
Clayton, Victoria, 3168
Germany4 sites
Private Practice - Dr. Frank Menzel
Dessau, 06846
Kath. St.-Johannes-Gesellschaft Dortmund
Dortmund, North Rhine-Westphalia, 44137
ClinPhenomics GmbH & Co KG
Frankfurt am Main, Hesse, 60596
Gemeinschaftpraxis Dr. med. Martin Prohaska und Dr. med. Felix Schulte
Mühldorf, Bavaria, 84453
United States3 sites
Care Access - Baltimore
Baltimore, Maryland, 21213
Care Access - Dorchester
Dorchester, Massachusetts, 02124
Care Access - Lima
Lima, Ohio, 45805
Netherlands2 sites
Meander Medisch Centrum
Amersfoort, Utrecht, 3813 TZ
VieCuri Medisch Centrum, locatie Venlo
Venlo, Limburg, 5912 BL
About this study
Official title: 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.
- Conditions
- Lipoprotein Disorder
- Being tested
- LY3473329, Placebo
- Keywords
- Atherosclerotic cardiovascular disease, ASCVD, Dyslipidemia, Lipoprotein(a), Lp(a), Cardiovascular, Cardiovascular disease, Cholesterol, Hyperlipidemia
- Medical subject headings
- Atherosclerosis, Dyslipidemias, Cardiovascular Diseases, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3473329Drug
Administered orally
PlaceboDrug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| 10 mg LY3473329 | Experimental | Participants received 10 milligrams (mg) of LY3473329 administered orally once daily (QD) over a 12-week treatment period. Receives: Drug: LY3473329 |
| 60 mg LY3473329 | Experimental | Participants received 60 mg of LY3473329 administered orally QD over a 12-week treatment period. Receives: Drug: LY3473329 |
| 240 mg LY3473329 | Experimental | Participants received 240 mg of LY3473329 administered orally QD over a 12-week treatment period. Receives: Drug: LY3473329 |
| Placebo | Placebo comparator | Participants received a matching dose of placebo administered orally QD over a 12-week treatment period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, Week 12
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week from randomization 1, 2, 8, 12: Pre-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study start24 Nov 2022
- Primary completion14 Mar 2024
- Study completion14 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lipoprotein DisorderStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05563246
- Sponsor's protocol ID
- 18495
- Other IDs
- J2O-MC-EKBC, 2022-501466-21-00
- Acronym
- KRAKEN
- Status last verified
- Mar 2025
- First submitted
- 28 Sep 2022
- Last updated
- 25 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39556768Nicholls 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.
PubMed 39329200Karp 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.
PubMed 38415744