A Study of Lepodisiran (LY3819469) in Adults With Elevated Lipoprotein(a) - ACCLAIM-Lp(a)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eli Lilly & Co.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Sep 2024 → ongoing

Decision date (initial)

2024-05-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509190-23-00

WHO UTN

U1111-1301-4368

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Pharmacogenomic, Efficacy, Pharmacodynamic, Safety, Pharmacoeconomic

Demonstrate whether lepodisiran is superior to placebo in
reducing the risk of the composite endpoint of MACE-4,
defined as
CV death
Non-fatal myocardial infarction
Non-fatal ischemic stroke, and
Urgent coronary revascularization.

Conditions and MedDRA coding

Atherosclerotic Cardiovascular Disease Elevated lp(a)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Have Lipoprotein(a) [Lp(a)] ≥175 nanomoles per liter (nmol/L) at pre-screening visit or screening visit as measured by the central laboratory.
2. Have disease characteristics of either 2a or 2b: 2a: Individuals 18 years of age or older with established atherosclerotic cardiovascular disease (ASCVD) with an event or revascularization ≥ 60 days before screening visit. Established ASCVD with history of an event or revascularization is defined as meeting at least one of the following: coronary artery disease; cerebral vascular disease, or peripheral arterial disease. 2b: Individuals 55 years of age or older who are at risk for a first cardiovascular (CV) events (i.e., have not had a prior CV event or revascularization) with the following required number of risk factors for first CV event at screening visit.
3. Must be 55 years or older and have 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 three or more high-risk factors.

Exclusion criteria 8

1. Have had a major cardiovascular event, such as myocardial infarction (MI), stroke or coronary or peripheral revascularization, or major surgery < 60 days before screening Visit 1 or between the screening Visit 1 and the randomization Visit 2.
2. Have uncontrolled hypertension at screening Visit 1 of • Systolic Blood Pressure (SBP) ≥180 millimeter of mercury (mm Hg) or • Diastolic Blood Pressure (DBP) ≥110 mm Hg.
3. Have New York Heart Association class IV heart failure.
4. Within 5 years of screening Visit 1, have a known coronary artery calcium score of 0, (this criterion applies only if participant has no evidence of ASCVD, specifically no history of ASCVD event or revascularization and has not had documented CAD or PAD).
5. Have lipoprotein apheresis within 90 days of screening, or planned lipoprotein apheresis during the study.
6. 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
7. Have a diagnosis of active nephrotic syndrome, or urine albumin-creatinine ratio (UCAR) of ≥5000 mg/g at screening Visit 1.
8. Have acute or chronic hepatitis, known cirrhosis, signs and symptoms of any liver disease other than metabolic-associated steatotic liver disease, formerly nonalcoholic fatty liver disease, or any of these laboratory results as determined by the central laboratory at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Time to First Occurrence Any Component of Major Adverse Cardiac Event (MACE)-4

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eli Lilly & Co.

Sponsor organisation

Eli Lilly & Co.

Address

1 Lilly Corporate Center

City

Indianapolis

Postcode

46285-0001

Country

United States

Scientific contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Public contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Third parties 14

Locations

14 EU/EEA countries · 303 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 375 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

25 submissions — initial application plus substantial / non-substantial modifications