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)

• ClinicalTrials.gov Identifier: NCT06292013
• Recruitment Status: Recruiting
• First Posted: March 4, 2024
• Last Update Posted: May 28, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: February 27, 2024
• First Posted Date: March 4, 2024
• Last Update Posted Date: May 28, 2024
• Actual Study Start Date: March 5, 2024
• Estimated Primary Completion Date: March 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2024)

Time to First Occurrence of Any Component of the Major Adverse Cardiac Event (MACE)-4 Composite Endpoint [ Time Frame: Baseline up to End of Study (About 4.5 Years) ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 1, 2024)

• Change from Baseline in Lipoprotein(a) [Lp(a)] at Week 4 [ Time Frame: Baseline, Week 4 ]
  Change from Baseline in Lp(a)
• Time to First Occurrence of Any of the Component of MACE-3 Composite Endpoint [ Time Frame: Baseline up to End of Study (About 4.5 Years) ]
  Time to first occurrence MACE-3
• 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 first occurrence of fatal or non-fatal myocardial infarction.
• Time to Cardiovascular Death [ Time Frame: Baseline up to End of Study (About 4.5 Years) ]
  Time to cardiovascular death.
• Time to Occurrence of All-Cause Death [ Time Frame: Baseline up to End of Study (About 4.5 Years) ]
  Time to occurrence of all-cause death
• 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 Frame: Baseline up to End of Study (About 4.5 Years) ]
  Time to first occurrence of any component of the MACE-4 composite endpoint.
• Time to First Occurrence of any Component of the MACE-4 Composite Endpoint (In the Population At Risk for First CV event) [ 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.
• Time to First Occurrence of any Component of the MACE-4 Composite Endpoint (In the Population with Lp(a) ≥ 200 nmol/L) [ 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.
• 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 MACE-3 + MALE 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) ]
  Time to first Occurrence of any component of coronary MACE-3 composite endpoint.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) Who Have Established Atherosclerotic Cardiovascular Disease or Are at Risk for a First Cardiovascular Event - ACCLAIM-Lp(a)
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Atherosclerotic Cardiovascular Disease (ASCVD)
• Elevated Lp(a)

Intervention

• Drug: Lepodisiran Sodium
  Administered SC
  Other Name: LY3819469
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: Lepodisiran Sodium
  Lepodisiran sodium administered subcutaneously (SC).
  Intervention: Drug: Lepodisiran Sodium
• Placebo Comparator: Placebo
  Placebo administered SC.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 1, 2024): 12500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2029
• Estimated Primary Completion Date: March 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, < 90 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, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease, or any of these laboratory results as determined by the central laboratory at screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Romania, Slovakia, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT06292013
• Other Study ID Numbers: 18812; J3L-MC-EZEF ( Other Identifier: Eli Lilly and Company ); 2023-509190-23 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and 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.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: 1-877-CTLILLY (1-877-285-4559) or 317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 2024