Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction (LIBerate-OLE)

Open-Label Extension Phase 3 Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Patients With HoFH and HeFH, CVD, or at High Risk for CVD, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction

The study is to assess the long-term safety, tolerability, and efficacy after 48 and 72 weeks with monthly (Q4W [<31 days]) dosing of subcutaneous (SC) LIB003 300 mg administered in patients with CVD or at high risk for CVD (including HoFH and HeFH) on stable diet and oral LDL-C lowering drug therapy who completed one of the LIB003 Phase 3 base studies.

Study Overview

• Status: Enrolling by invitation
• Conditions: Familial Hypercholesterolemia; Elevated Cholesterol; Cardiovascular Disease With Mention of Arteriosclerosis
• Intervention / Treatment: Drug: lerodalcibep

Detailed Description

The population for this open-label study includes patients who successfully complete one of the randomized, controlled (placebo or comparator) blinded Phase 3 base studies (LIB003-003, LIB003-004, LIB003-005, LIB003-006, LIB003-008, LIB003-011 and LIB003-012). Patients will continue to maintain their existing oral lipid-lowering therapy (LLT).

Following completion of a base study and providing informed consent, patients will receive doses of LIB003 300 mg Q4W (<31 days) on Day 1 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, and 68. Patients will be seen in the clinic Q4W (<31 days) for at least the initial 12 weeks and then every 12 weeks (Weeks 24, 36, 48, 60, and 72) with the interim Q4W (<31 days) doses administered at home.

Patients may begin the OLE on the final visit of their prior study after completion of all requirements for that trial. Their lipids will remain blinded (to patient, study staff and sponsor) until week 4 to avoid any unblinding of the prior trial. Thereafter lipid results will be unblinded throughout the remainder of the 72 week trial.

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • New Delhi, India, 110002
    • G.B. Pant Institute of Postgraduate Medical Education & Research
• Israel
  • Jerusalem, Israel, 12000
    • Department of Medicine, Hadassah University Hospital
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center, Beilinson Hospital,
• Norway
  • Oslo, Norway, 0586
    • Lipid Clinic, Oslo University Hospital
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Carbohydrate and Lipid Metabolism Research Unit
  • Western Province
    • Cape Town, Western Province, South Africa, 7925
      • Division of Lipidology, Department of Medicine University of Cape Town
• Turkey
  • Afyon, Turkey
    • Afyonkarahisar Health Sciences University
  • Bornova
    • İzmir, Bornova, Turkey, 35040
      • Ege University Medical School
• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group
    • Cincinnati, Ohio, United States, 45227
      • Metabolic & Atherosclerosis Research Center (MARC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Successful completion 1 of one of the Phase 3 base studies LIB003-003, LIB003-004, LIB003-005, LIB003-006, LIB003-008, LIB003-011 and LIB003-012 without SAEs related to LIB003; or
• Provision of written and signed informed consent prior to any study-specific procedure;
• Female patients of childbearing potential must be using a highly effective form of birth control if sexually active and have a negative urine pregnancy test on Day 1 prior to dosing;
• Patient is willing to maintain appropriate diet and stable dose of current lipid-lowering therapy including statins, ezetimibe, bile acid sequestrants, niacin, bempedoic acid, bezafibrate or fenofibrate, and/or OM-3 compounds; and
• Patient is considered by the Investigator to be otherwise healthy,

Exclusion Criteria:

• Failure to complete a base Phase 3 (LIB003-003, LIB003-004, LIB003-005, LIB003-006, LIB003-008, LIB003-011 and LIB003-012) study and/or had an SAE that was related to study drug during the base Phase 3 study;
• Development since the final visit in the base Phase 3 (LIB003-003, LIB003-004, LIB003-005, LIB003-006, LIB003-008, LIB003-011 or LIB003-012) study of any concomitant clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator,
• Use of prohibited oral lipid-lowering agents PCSK9 mAbs, mipomersen, lomitapide gemfibrozil (or bempedoic acid for LIB003, -011) following the base study or the use of PCSK9 short interfering ribonucleic acid (siRNA), or locked nucleic acid-reducing agents (LNA) within the last 6 months;
• Not available for protocol-required study visits or procedures, to the best of the patient's and Investigator's knowledge;
• Has any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LIB003 (lerodalcibep); 300 mg monthly (Q4W) by subcutaneous injection	Drug: lerodalcibep; PCSK9 inhibitor; Other Names: LIB003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 48 and 72 weeks	Evaluation of Adverse Events based on MedRA based on ITT population	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Incidence of anti-drug antibodies	72 weeks
LDL Cholesterol reduction	Percent decrease in LDL-C from baseline of original study	72 weeks

Collaborators and Investigators

• Sponsor: LIB Therapeutics LLC
• Collaborators: Medpace, Inc.
• Investigators: Study Director: David Kallend, MB BCh, LIB Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: lerodalcibep; PCSK9 inhibitor
• Additional Relevant MeSH Terms: Vascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Arterial Occlusive Diseases; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Cardiovascular Diseases; Hypercholesterolemia; Arteriosclerosis; Hyperlipoproteinemia Type II
• Other Study ID Numbers: LIB003-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No