Trial to Evaluate Efficacy and Safety of LIB003, Evolocumab and Alirocumab in High-risk CVD Patients (LIBerate-H2H)

• ClinicalTrials.gov Identifier: NCT04790513
• Recruitment Status: Active, not recruiting
• First Posted: March 10, 2021
• Last Update Posted: July 14, 2022
• Sponsor: LIB Therapeutics LLC
• Information provided by (Responsible Party): LIB Therapeutics LLC

Study Description

Brief Summary:

Comparison of LDL-C reductions at Week 12 of monthly (Q4W[≤ 31 days]) dosing of LIB003 300 mg administered subcutaneously (SC) to Q4W dosing of evolocumab (Repatha) 420 mg and alirocumab (Praluent) 300 mg in patients with CVD or at high risk for CVD on a stable diet and high intensity statin and other LDL-C-lowering drug therapy.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia; Cardiovascular Diseases	Biological: lerodalcibep; Biological: evolocumab; Biological: alirocumab	Phase 3

Detailed Description:

This is a randomized, open-label Phase 3 study of 12 weeks duration comparing Q4W SC doses of LIB003 300 mg, evolocumab (Repatha) 420 mg and alirocumab (Praluent) 300 mg. Approximately 220 males and females aged ≥18 years who fulfill all of the inclusion and exclusion criteria will be enrolled at up to 25 sites in the United States. Patients will be stratified by baseline LDL-C and randomized in a 2:2:1 ratio to LIB003 (88 patients), Repatha (88 patients) or Praluent (44 patients) administered SC Q4W (≤31 days). The study will consist of a Screening Period and a Treatment Period. The total study duration will be up to 21 weeks which includes up to 9-week Screening Period (depending on period required for washout of PCSK9 mAb and/or intensification of statin treatment) and 12 weeks of study drug treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized, open-label with blinded lipid levels
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: lipid levels measured and central laboratory will be blinded to participants, investigators, and sponsor, DSMB and CEC (Cardiovascular Events Committee)
• Primary Purpose: Treatment
• Official Title: Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and Safety of LIB003, Evolocumab and Alirocumab in CVD Patients, or at High Risk for CVD, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction (LIBerate-H2H)
• Actual Study Start Date: April 22, 2021
• Estimated Primary Completion Date: August 30, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: LIB003 (lerodalcibep); 300 mg SC Q4W	Biological: lerodalcibep; anti-PCSK9 small binding protein; Other Name: LIB003
Active Comparator: evolocumab; 420 mg SC Q4W	Biological: evolocumab; monoclonal antibody to PCSK9; Other Name: Repatha
Active Comparator: alirocumab; 300 mg SC Q4W	Biological: alirocumab; monoclonal antibody to PCSK9; Other Name: Praluent

Outcome Measures

Primary Outcome Measures :

1. LDL-C reduction from baseline at 12 weeks [ Time Frame: 12 weeks ]
   LS Mean percent change from baseline to week 12

Secondary Outcome Measures :

1. Achieved ESC/EAS LDL-C goals [ Time Frame: 12 weeks ]
   Percent of patients achieving ESC/EAS 2019 LDL-C target
2. tolerability and safety of each treatment: injection site reactions [ Time Frame: 12 weeks ]
   ISR (injection site reactions) after each dose

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• signed informed consent
• diagnosed with CVD or a high risk of CVD based on 2019 ESC/EAS guidelines
• Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2
• LDL-C ≥90 mg/dL and TG ≤400 mg/dL while on stable diet & lipid-lowering oral drug therapy (ie, high intensity statin with or without ezetimibe) and no PCSK9 mAb for 4 weeks if previously on Q2W dosing or 8 weeks if on Q4W dosing.
• Females of childbearing potential must be using a highly effective form of birth control if sexually active and have a negative urine pregnancy test at the last Screening Visit

Exclusion Criteria:

• at screening visit: not on high intensity statin; mipomersen or lomitapide within 6 months; gemfibrozil within 6 weeks; bempedoic acid within 4 weeks; inclisiran within 12 months; apheresis within 8 weeks
• HoFH defined clinically and/or genetically
• History of prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator
• estimated glomerular filtration rate <30 mL/min/1.73m2 at screening
• Active liver disease or hepatic dysfunction, history of liver transplant, and/or AST or ALT >2.5 × the ULN
• Uncontrolled Type 1 or Type 2 diabetes mellitus, defined as fasting glucose ≥200 mg/dL or glycated hemoglobin (HbA1c) of ≥9%
• NY Heart Association class III-IV heart failure; or patients with last documented left ventricular ejection fraction <30%; planned PCI, CABG or cardiac surgery
• Uncontrolled hypertension defined as evidenced by a reproducible (repeated 5 minutes apart) sitting blood pressure ≥160 mmHg systolic or ≥100 mmHg diastolic;
• Enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives since ending another investigational device or drug study(ies), or receiving PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months of the Screening Visit;
• Have any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study;

Contacts and Locations

Locations

United States, Ohio

Sterling Research Group

Cincinnati, Ohio, United States, 45219

The Lindner Research Center

Cincinnati, Ohio, United States, 45219

Metabolic & Atherosclerosis Research Center (MARC)

Cincinnati, Ohio, United States, 45227

Sponsors and Collaborators

LIB Therapeutics LLC

Investigators

• Study Director: Evan A Stein, MD PhD; LIB Therapeutics

More Information

• Responsible Party: LIB Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT04790513
• Other Study ID Numbers: LIB003-011
• First Posted: March 10, 2021
• Last Update Posted: July 14, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by LIB Therapeutics LLC:

lerodalcibep; evolocumab; alirocumab

Additional relevant MeSH terms:

Cardiovascular Diseases; Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Evolocumab; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents