Clinical trial NCT05563246: A Study of LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lipoprotein Disorder
Keywords: Atherosclerotic cardiovascular disease
ASCVD
Dyslipidemia
Lipoprotein(a)
Lp(a)
Cardiovascular
Cardiovascular disease
Cholesterol
Hyperlipidemia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-10-03
Enrollment: 233
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Lp(a) - Assessed Via Intact Lp(a) Assay
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Lp(a) - Assessed Via Apo(a) Assay
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Intact Lp(a) Assay
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Apo(a) Assay
timeFrame: Week 12
measure: Percent Change From Baseline in Apolipoprotein B (ApoB)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
timeFrame: Baseline, Week 12
measure: Pharmacokinetics (PK): Trough Concentrations (C-trough) of LY3473329
timeFrame: Week from randomization 1, 2, 8, 12: Pre-dose
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Care Access - Baltimore
state: Maryland
city: Dorchester
country: United States
facility: Care Access - Dorchester
state: Massachusetts
city: Lima
country: United States
facility: Care Access - Lima
state: Ohio
city: Brisbane
country: Australia
facility: Core Research Group
state: Queensland
city: Adelaide
country: Australia
facility: Nightingale Research
state: South Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Victorian Heart Hospital
state: Victoria
city: Vitória
country: Brazil
facility: CEDOES
state: Espírito Santo
city: Curitiba
country: Brazil
facility: Pesquisa Clínica em Diabetes - Dra Rosângela Réa
state: Paraná
city: Acaraju
country: Brazil
facility: Centro de Pesquisa Clinica do Coracao
state: Sergipe
city: Sao Paulo
country: Brazil
facility: Incor - Instituto do Coracao
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: IBPClin - Instituto Brasil de Pesquisa Clínica
city: Sao Paulo
country: Brazil
facility: CPCLIN
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiology
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica
city: Sanya
country: China
facility: Third People's Hospital of Hainan Province
state: Hainan
city: Harbin
country: China
facility: The First Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The Fourth Hospital of Harbin Medical University
state: Heilongjiang
city: Changzhou
country: China
facility: Changzhou Second People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Mühldorf
country: Germany
facility: Gemeinschaftpraxis Dr. med. Martin Prohaska und Dr. med. Felix Schulte
state: Bayern
city: Frankfurt
country: Germany
facility: ClinPhenomics GmbH & Co KG
state: Hessen
city: Dortmund
country: Germany
facility: Kath. St.-Johannes-Gesellschaft Dortmund
state: Nordrhein-Westfalen
city: Dessau
country: Germany
facility: Private Practice - Dr. Frank Menzel
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
state: Csongrád
city: Nyiregyhaza
country: Hungary
facility: Medifarma 98 Kft
state: Nyíregyháza
city: Kistarcsa
country: Hungary
facility: Flor Ferenc Hospital of Pest County
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Belvárosi Egészségház
state: Zala
city: Budapest
country: Hungary
facility: Dél-Pesti Centrumkórház
city: Budapest
country: Hungary
facility: Semmelweis University
city: Funabashi
country: Japan
facility: Funabashi Municipal Medical Center
state: Chiba
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Morioka
country: Japan
facility: Iwate Prefectural Central Hospital
state: Iwate
city: Suita-shi
country: Japan
facility: Medical Corporation Heishinkai OCROM Clinic
state: Osaka
city: Hachioji
country: Japan
facility: Minamino Cardiovascular Hospital
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima City Hospital
city: Miyazaki
country: Japan
facility: Miyazaki Medical Association Hospital
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum, locatie Venlo
state: Limburg
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
state: Utrecht
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: