Trial to Evaluate Efficacy and Safety of LIB003 and Inclisiran in High-risk CVD Patients (LIBerate-VI)

Randomized Open Label, Phase 3 Study to Compare the Efficacy and Safety of Lerodalcibep (LIB003) to Inclisiran in Patients at Very High or High Risk for CVD, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction

Comparison of LDL-C reductions of lerodalcibep (LIB003) 300 mg to inclisiran (Leqvio®) 284 in patients at very-high risk or high-risk for CVD on stable diet and oral LDL-C-lowering drug therapy

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia; Atherosclerotic Ischemic Disease
• Intervention / Treatment: Biological: lerodalcibep; Drug: Inclisiran

Detailed Description

Randomized, Open Label (lipids blinded), Phase 3 Study to Evaluate the Efficacy and Safety of Lerodalcibep (LIB003) at Day 270 of subcutaneous (SC) monthly (QM [≤31 days]) lerodalcibep (LIB003) 300 mg administered to SC inclisiran (Leqvio®) 284 mg at Days 1 and 90 in patients with very-high risk or high-risk CVD or at high risk for CVD with LDL-C ≥85 mg/dL on a stable diet and oral LDL-C-lowering drug therapy

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Cedex 01
    • Nantes, Cedex 01, France, 44093
      • CHU de Nantes - Hopital Nord Laennec
  • Cedex 05
    • Marseille, Cedex 05, France, 13385
      • Hôpitaux de Marseille
• Germany
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg - Medizinische Klinik
• Norway
  • Nydalen
    • Oslo, Nydalen, Norway, 424
      • The Lipid Clinic (Oslo University Hospital)
• Spain
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• United Kingdom
  • Cornwall
    • Liskeard, Cornwall, United Kingdom, PL14 3XA
      • Oak Tree Surgery and Pensilva Health Centre
  • Lancashire
    • Ashton-Under-Lyne, Lancashire, United Kingdom, OL6 6EW
      • Ashton Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed informed consent prior to any study-specific procedure;
• Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥16 and ≤42 kg/m2;
• Very- high or high risk for CVD as defined in 2019 ESC/EAS Guidelines
• High-intensity statin (daily atorvastatin 40/80 or rosuvastatin 20/40) without other acceptable oral lipid lowering treatment plus diet; stable >4 weeks with LDL-C ≥85 mg/dL and triglycerides ≤400 mg/dL
• Women of childbearing potential (WOCBP) must continue using a highly effective form of birth control if sexually active
• Males whose partners are of CBP and not using a highly effective form of birth control will either be surgically sterile or agree to use the following forms of contraception, male or female condom with spermicide

Exclusion Criteria:

• Prior or active clinical condition or acute and/or unstable systemic disease, including cancer, compromising patient inclusion or preclude completion of the study, at the discretion of the Investigator
• Homozygous FH
• non-high intensity statins, mipomersen, lomitapide, gemfibrozil, and bempedoic acid
• PCSK9 mAb within 4 weeks of screening or siRNA within 1 year
• Severe renal dysfunction, defined eGFR <30 ml/min
• Recent, within 3 months of screening, atherosclerotic event or intervention
• planned cardiac procedure
• NYHA class III or IV heart failure
• active liver disease
• uncontrolled diabetes defined as fasting glucose >200 mg/dL and HbA1c > 9%
• uncontrolled BP ≥180 mmHg systolic or ≥110 mmHg diastolic;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lerodalcibep; 300 mg SC dosed monthly	Biological: lerodalcibep; 300 mg; Other Names: LIB003
Active Comparator: inclisiran; 284 mg SC dosed Day 1 and Day 90	Drug: Inclisiran; 284 mg; Other Names: Leqvio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-C change	Percent LDL-C change from baseline	Day 270

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	frequency and severity of injection site reactions (ISRs)	270 days
Serum free PCSK9 levels	Percent change in free PCSK9 from baseline	Day 270
Apolipoproteins	Percent change in Apo B and Lp(a) from baseline	Day 270
Treatment goal achievement	Percent of patients reaching ESC/EAS treatment goals	Day 270

Collaborators and Investigators

• Sponsor: LIB Therapeutics LLC
• Collaborators: Medpace, Inc.
• Investigators: Study Director: Evan A Stein, MD PhD, LIB Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Actual): May 30, 2024
• Study Completion (Actual): October 15, 2024

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: lerodalcibep; PCSK9 inhibitor; inclisiran
• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Hypercholesterolemia
• Other Study ID Numbers: LIB003-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No