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

NCT04790513 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: LIB003-011
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 3

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.

Conditions

Hypercholesterolemia; Cardiovascular Diseases

Keywords

lerodalcibep; evolocumab; alirocumab

Outcome Measures

Primary Outcomes (1)

• LDL-C reduction from baseline at 12 weeks

  LS Mean percent change from baseline to week 12

  12 weeks

Secondary Outcomes (2)

• Achieved ESC/EAS LDL-C goals

  12 weeks

• tolerability and safety of each treatment: injection site reactions

  12 weeks

Study Arms (3)

LIB003 (lerodalcibep)

EXPERIMENTAL

300 mg SC Q4W

Biological: lerodalcibep

evolocumab

ACTIVE COMPARATOR

420 mg SC Q4W

Biological: evolocumab

alirocumab

ACTIVE COMPARATOR

300 mg SC Q4W

Biological: alirocumab

Interventions

lerodalcibep BIOLOGICAL

anti-PCSK9 small binding protein

Also known as: LIB003

LIB003 (lerodalcibep)

evolocumab BIOLOGICAL

monoclonal antibody to PCSK9

Also known as: Repatha

evolocumab

alirocumab BIOLOGICAL

monoclonal antibody to PCSK9

Also known as: Praluent

alirocumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• LIB Therapeutics LLC: lead

Study Sites (3)

Sterling Research Group

Cincinnati, Ohio, 45219, United States

Location

The Lindner Research Center

Cincinnati, Ohio, 45219, United States

Location

Metabolic & Atherosclerosis Research Center (MARC)

Cincinnati, Ohio, 45227, United States

Location

MeSH Terms

Conditions

Hypercholesterolemia; Cardiovascular Diseases

Interventions

evolocumab; alirocumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Evan A Stein, MD PhD

  LIB Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: lipid levels measured and central laboratory will be blinded to participants, investigators, and sponsor, DSMB and CEC (Cardiovascular Events Committee)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, open-label with blinded lipid levels

Study Record Dates

• First Submitted: March 6, 2021
• First Posted: March 10, 2021
• Study Start: April 22, 2021
• Primary Completion: September 30, 2022
• Study Completion: December 31, 2022
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)