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

Sponsor

LIB Therapeutics LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04790513

Collaborator

(none)

204

Enrollment

Locations

Arms

18.3

Anticipated Duration (Months)

Patients Per Site

3.7

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

204 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, open-label with blinded lipid levelsrandomized, 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 :

Apr 22, 2021

Anticipated Primary Completion Date :

Aug 30, 2022

Anticipated Study Completion Date :

Oct 31, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: LIB003 (lerodalcibep)

300 mg SC Q4W

Biological: lerodalcibep

anti-PCSK9 small binding protein

Other Names:

LIB003

Active Comparator: evolocumab

420 mg SC Q4W

Biological: evolocumab

monoclonal antibody to PCSK9

Other Names:

Repatha

Active Comparator: alirocumab

300 mg SC Q4W

Biological: alirocumab

monoclonal antibody to PCSK9

Other Names:

Praluent

Outcome Measures

Primary Outcome Measures

LDL-C reduction from baseline at 12 weeks [12 weeks]
LS Mean percent change from baseline to week 12

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Sterling Research Group	Cincinnati	Ohio	United States	45219
2	The Lindner Research Center	Cincinnati	Ohio	United States	45219
3	Metabolic & Atherosclerosis Research Center (MARC)	Cincinnati	Ohio	United States	45227