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

• ClinicalTrials.gov Identifier: NCT04798430
• Recruitment Status: Enrolling by invitation
• First Posted: March 15, 2021
• Last Update Posted: March 29, 2023
• Sponsor: LIB Therapeutics LLC
• Collaborator: Medpace, Inc.
• Information provided by (Responsible Party): LIB Therapeutics LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Disease With Mention of Arteriosclerosis; Elevated Cholesterol; Familial Hypercholesterolemia	Drug: lerodalcibep	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2000 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: open label extension trial
• Masking: None (Open Label)
• Masking Description: lipids blinded to participant, investigator and sponsor at Day 1 only
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 3, 2020
• Estimated Primary Completion Date: October 30, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: LIB003 (lerodalcibep); 300 mg monthly (Q4W) by subcutaneous injection	Drug: lerodalcibep; PCSK9 inhibitor; Other Name: LIB003

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Immunogenicity [ Time Frame: 72 weeks ]
   Incidence of anti-drug antibodies
2. LDL Cholesterol reduction [ Time Frame: 72 weeks ]
   Percent decrease in LDL-C from baseline of original study

Eligibility Criteria

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

Criteria

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;

Contacts and Locations

Locations

United States, Illinois

NorthShore University Health System

Evanston, Illinois, United States, 60201

United States, Ohio

Sterling Research Group

Cincinnati, Ohio, United States, 45219

The Lindner Research Center

Cincinnati, Ohio, United States, 45219

Metabolic & Atherosclerosis Research Center (MARC)

Cincinnati, Ohio, United States, 45227

India

G.B. Pant Institute of Postgraduate Medical Education & Research

New Delhi, India, 110002

Israel

Department of Medicine, Hadassah University Hospital

Jerusalem, Israel, 12000

Rabin Medical Center, Beilinson Hospital,

Petah Tikva, Israel, 49100

Norway

Lipid Clinic, Oslo University Hospital

Oslo, Norway, 0586

South Africa

Carbohydrate and Lipid Metabolism Research Unit

Johannesburg, Gauteng, South Africa, 2193

Division of Lipidology, Department of Medicine University of Cape Town

Cape Town, Western Province, South Africa, 7925

Turkey

Ege University Medical School

İzmir, Bornova, Turkey, 35040

Afyonkarahisar Health Sciences University

Afyon, Turkey

Sponsors and Collaborators

LIB Therapeutics LLC

Medpace, Inc.

Investigators

• Study Director: David Kallend, MB BCh; LIB Therapeutics

More Information

• Responsible Party: LIB Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT04798430
• Other Study ID Numbers: LIB003-007
• First Posted: March 15, 2021
• Last Update Posted: March 29, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by LIB Therapeutics LLC:

lerodalcibep; PCSK9 inhibitor

Additional relevant MeSH terms:

Cardiovascular Diseases; Arteriosclerosis; Hyperlipoproteinemia Type II; Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hyperlipoproteinemias; Arterial Occlusive Diseases; Vascular Diseases