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

NCT04797104 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: LIB003-004
• Study Type: interventional
• Target: 478
• Locations: 5 countries
• Sites: 7

Brief 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.

Conditions

Heterozygous Familial Hypercholesterolemia

Keywords

lerodalcibep; PCSK9 inhibitor

Outcome Measures

Primary Outcomes (1)

• Change from baseline compared to placebo in LDL-C level

  LS mean percent change in LDL-cholesterol compared to placebo

  24 weeks

Secondary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities

  24 weeks

• Change in serum free PCSK9 with LIB003 compared to placebo

  24 weeks

Study Arms (2)

LIB003 (lerodalcibep)

EXPERIMENTAL

300 mg (1.2 mL) SC Q4W

Drug: lerodalcibep

Placebo

PLACEBO COMPARATOR

1.2 mL SC Q4W

Drug: lerodalcibep

Interventions

lerodalcibep DRUG

300 mg Q4W

Also known as: LIB003

LIB003 (lerodalcibep); Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• LIB Therapeutics LLC: lead
• Medpace, Inc.: collaborator

Study Sites (7)

Metabolic & Atherosclerosis Research Center (MARC)

Cincinnati, Ohio, 45227, United States

Location

Department of Medicine, Hadassah University Hospital

Jerusalem, 12000, Israel

Location

Rabin Medical Center, Beilinson Hospital,

Petah Tikva, 49100, Israel

Location

Lipid Clinic, Oslo University Hospital

Oslo, 0586, Norway

Location

Carbohydrate and Lipid Metabolism Research Unit

Johannesburg, Gauteng, 2193, South Africa

Location

Division of Lipidology, Department of Medicine University of Cape Town

Cape Town, Western Province, 7925, South Africa

Location

Ege University Medical School

Izmir, Bornova, 35040, Turkey (Türkiye)

Location

Study Officials

• David Kallend, MB BCh

  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: double blind to treatment (LIB003 or placebo) and lipid data
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized double blind placebo controlled

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 15, 2021
• Study Start: April 22, 2021
• Primary Completion: July 30, 2023
• Study Completion: December 5, 2023
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (2); TU (1); NO (1); US (1); IL (2)