Clinical trial NCT04790513: Trial to Evaluate Efficacy and Safety of LIB003, Evolocumab and Alirocumab in High-risk CVD Patients
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Cardiovascular Diseases
Keywords: lerodalcibep
evolocumab
alirocumab
Lead sponsor: LIB Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2021-03-10
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, open-label with blinded lipid levels
Primary purpose: TREATMENT

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.

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.

Eligibility 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;

Primary outcomes:
measure: LDL-C reduction from baseline at 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Achieved ESC/EAS LDL-C goals
timeFrame: 12 weeks
measure: tolerability and safety of each treatment: injection site reactions
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Cincinnati
country: United States
facility: The Lindner Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Metabolic & Atherosclerosis Research Center (MARC)
state: Ohio
Study officials:
affiliation: LIB Therapeutics
name: Evan A Stein, MD PhD
role: STUDY_DIRECTOR
References: