Study to Assess the Efficacy and Safety of LIB003 in HeFH Patients on Oral Lipid Therapy Needing Further LDL-C Reduction

Heterozygous Familial Hypercholesterolemia Clinical Trial

— LIBerate-FH  

Official title:

Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Heterozygous FH Patients on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04797104
• Other study ID #: LIB003-004
• Status: Completed
• Phase: Phase 3
• Start date: April 22, 2021
• Est. completion date: December 5, 2023

Study information

• Verified date: December 2023
• Source: LIB Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to assess LDL-C reductions at Week 24 and the mean of Weeks 22 and 24 with monthly Q4W (≤31 days) dosing of LIB003 300 mg administered subcutaneously (SC) compared to placebo in patients 18 years or older with Heterozygous FH on stable diet and oral LDL-C lowering drug therapy.

Description:

A randomized, double-blind, placebo-controlled, Phase 3 study of 24 weeks duration. Approximately 600 males and females aged ≥18 years with clinical or genetic heterozygous FH who fulfill the inclusion and exclusion criteria will be enrolled. Patients will be randomized in a 2:1 ratio to LIB003 (400 patients) or placebo (200 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 35 weeks which includes up to an 11-week Screening Period (which may include up to a 8-week washout) and 24 weeks of study drug treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 478
• Est. completion date: December 5, 2023
• Est. primary completion date: July 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provision of written and signed informed consent prior to any study-specific procedure;

• Weight of =40 kg (88 lbs) and body mass index (BMI) =17 and =42 kg/m2;

• Diagnosis of definite, probable or possible HeFH based either on clinical criteria (Simon Broome register criteria or Dutch Lipid Clinics [DLC] Network Criteria) or genotyping and at the defined eligibility visit (screening or post washout/stabilization)

• LDL-C =70 mg/dL (if very-high risk for CVD) or =100 mg/dL (if high risk for CVD) and TG =400 mg/dL while on stable lipid lowering oral drug therapy (eg, maximally tolerated statin with or without ezetimibe); Patients unable to tolerate approved doses of a statin may take lower than approved doses and less frequently than daily as long as the dose and dosing frequency is consistent.

• Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, and unable to tolerate any other allowed oral lipid lowering agent, and thus on no lipid lowering therapy must have an LDL-C =190 mg/dL (4.9 mmol/L) at the Screening Visit unless they have a documented pathogenic FH variant;

• Stable diet and other lipid lowering oral therapies besides statins and ezetimibe including bile-acid sequestrants, OM-3 compounds, fenofibrate, bezafibrate, nicotinic acid and bempedoic acid or combinations thereof for at least 4 weeks

• Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of =4 weeks after the last dose; for those on a dose of 300 mg or 420 mg Q4W (=31 days) the washout period is =8 weeks following last dose;

• Females of childbearing potential must be using a highly effective form of contraception if sexually active and have negative urine pregnancy test at the last Screening Visit

Exclusion Criteria:

• Use of prohibited oral lipid lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of the Screening Visit or LDL/plasma apheresis within 2 months prior to Day 1;

• Documented history of HoFH defined clinically or genetically

• History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator.

• Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit;

• Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2

• Active liver disease or hepatic dysfunction, history of liver transplant, and/or AST or ALT >2.5 × the ULN

• Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by TSH <LLN or >1.5 × ULN, respectively,

• Uncontrolled Type 1 or Type 2 DM (fasting glucose=200 mg/dL or HbA1c of =9%;

• Planned cardiac surgery or revascularization;

• New York Heart Association III-IV heart failure

• Previous treatment with LIB003 or any adnectin product;

• Any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study

Related Conditions & MeSH terms

• Heterozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• lerodalcibep
300 mg Q4W

Locations

Country	Name	City	State
Israel	Department of Medicine, Hadassah University Hospital	Jerusalem
Israel	Rabin Medical Center, Beilinson Hospital,	Petah Tikva
Norway	Lipid Clinic, Oslo University Hospital	Oslo
South Africa	Division of Lipidology, Department of Medicine University of Cape Town	Cape Town	Western Province
South Africa	Carbohydrate and Lipid Metabolism Research Unit	Johannesburg	Gauteng
Turkey	Ege University Medical School	Izmir	Bornova
United States	Metabolic & Atherosclerosis Research Center (MARC)	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
LIB Therapeutics LLC	Medpace, Inc.

Countries where clinical trial is conducted

United States,  Israel,  Norway,  South Africa,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline compared to placebo in LDL-C level	LS mean percent change in LDL-cholesterol compared to placebo	24 weeks
Secondary	Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities	Incidence of Treatment-Emergent Adverse Events (TEAE) as assessed by Medical Dictionary for Regulatory Activities as mild, moderate or severe compared to placebo	24 weeks
Secondary	Change in serum free PCSK9 with LIB003 compared to placebo	Change in percent LS mean between LIB003 and placebo	24 weeks