A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) - ACCLAIM-Lp(a)

Phase 3Active Not RecruitingNCT06292013

Eli Lilly and Company17,300 enrolled

Overview

The purpose of this study is to evaluate the efficacy of lepodisiran in reducing cardiovascular risk in participants with high lipoprotein(a) who have cardiovascular disease or are at risk of a heart attack or stroke. The study drug will be administered subcutaneously (SC) (under the skin). Approximately 1700 additional participants will be enrolled in an addendum to explore Lp(a) lowering with an alternative dosing schema.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

17,300

Conditions

Atherosclerotic Cardiovascular Disease (ASCVD)Elevated Lp(a)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have Lipoprotein(a) \[Lp(a)\] ≥175 nanomoles per liter (nmol/L). * Meet criteria of either 2a or 2b: 2a: Individuals 18 years of age or older with established atherosclerotic cardiovascular disease (ASCVD) with an event or revascularization. 2b: Individuals 55 years of age or older who are at risk for a first cardiovascular (CV) event and either: Documented coronary artery disease (CAD), carotid stenosis, or peripheral artery disease (PAD) without history of event or revascularization; known familial hypercholesteremia; or a combination of high-risk factors. Exclusion Criteria: * Have had a major cardiovascular event or surgery, such as myocardial infarction (MI), stroke or coronary or peripheral revascularization, \< 60 days before screening * Have uncontrolled hypertension * Have New York Heart Association class IV heart failure. * Have lipoprotein apheresis within 90 days of screening, or planned lipoprotein apheresis during the study. * Have severe renal failure, defined as * Estimated glomerular rate (eGFR) \<15 milliliters per minute per 1.73 meters squared (mL/min/1.73m2) at screening Visit 1, or ongoing dialysis. * Have a diagnosis of active nephrotic syndrome, or urine albumin-creatinine ratio (UACR) of ≥5000 mg/g at screening Visit 1. * Have acute or chronic hepatitis, known cirrhosis, signs and symptoms of any other liver disease other than metabolic-associated steatotic liver disease, or exclusionary laboratory results as determined by the central laboratory during screening.

Locations (932)

Birmingham Clinical Research

Birmingham, Alabama, United States

Alliance for Multispecialty Research, LLC

Daphne, Alabama, United States

SEC Clinical Research

Dothan, Alabama, United States

Alliance for Multispecialty Research, LLC

Mobile, Alabama, United States

Mobile Heart Specialists

Mobile, Alabama, United States

Outcomes

Primary Outcomes

Time to First Occurrence of Any Component of the Major Adverse Cardiac Event (MACE)-4 Composite Endpoint

Time to first event in a MACE-4 composite endpoint, comprised of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent coronary revascularization.

Time frame: Baseline up to End of Study (About 4.5 Years)

Secondary Outcomes

Change from Baseline in Lipoprotein(a) [Lp(a)] at Week 4

Change from Baseline in Lp(a)

Time frame: Baseline, Week 4

Time to First Occurrence of Any of the Component of MACE-3 Composite Endpoint

Time to first occurrence MACE-3

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to First Occurrence of Fatal or Non-Fatal Myocardial Infarction

Time to first occurrence of fatal or non-fatal myocardial infarction.

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to Cardiovascular Death

Time to cardiovascular death.

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to Occurrence of All-Cause Death

Time to occurrence of all-cause death

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to First Occurrence of Any Component of the MACE-4 Composite Endpoint (In the Population with Established ASCVD and CV Event, or Revascularization)

Time to first occurrence of any component of the MACE-4 composite endpoint.

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to First Occurrence of any Component of the MACE-4 Composite Endpoint (In the Population At Risk for First CV event)

Time to first occurrence of any component of the MACE-4 composite endpoint.

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to First Occurrence of any Component of the MACE-4 Composite Endpoint (In the Population with Lp(a) ≥ 200 nmol/L)

Time to first occurrence of any component of the MACE-4 composite endpoint.

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to First Occurrence of Any Component of MACE-3 + MALE Composite Endpoint

Time to first occurrence of any component of MACE-3 + MALE composite endpoint.

Time frame: Baseline up to End of Study (About 4.5 Years)

Time to First Occurrence of Any Component of Coronary MACE-3 Composite Endpoint

Time to first Occurrence of any component of coronary MACE-3 composite endpoint.

Time frame: Baseline up to End of Study (About 4.5 Years)