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

Phase 3
Conditions
Cardiovascular Disease With Mention of Arteriosclerosis
Elevated Cholesterol
Familial Hypercholesterolemia
Interventions
Registration Number
NCT04798430
Lead Sponsor
LIB Therapeutics LLC
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.

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.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
2000
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LIB003 (lerodalcibep)lerodalcibep300 mg monthly (Q4W) by subcutaneous injection
Primary Outcome Measures
NameTimeMethod
Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 48 and 72 weeks72 weeks

Evaluation of Adverse Events based on MedRA based on ITT population

Secondary Outcome Measures
NameTimeMethod
Immunogenicity72 weeks

Incidence of anti-drug antibodies

LDL Cholesterol reduction72 weeks

Percent decrease in LDL-C from baseline of original study

Trial Locations

Locations (12)

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

🇮🇳

New Delhi, India

Rabin Medical Center, Beilinson Hospital,

🇮🇱

Petah Tikva, Israel

Department of Medicine, Hadassah University Hospital

🇮🇱

Jerusalem, Israel

Ege University Medical School

🇹🇷

İzmir, Bornova, Turkey

Lipid Clinic, Oslo University Hospital

🇳🇴

Oslo, Norway

Afyonkarahisar Health Sciences University

🇹🇷

Afyon, Turkey

Division of Lipidology, Department of Medicine University of Cape Town

🇿🇦

Cape Town, Western Province, South Africa

Metabolic & Atherosclerosis Research Center (MARC)

🇺🇸

Cincinnati, Ohio, United States

Carbohydrate and Lipid Metabolism Research Unit

🇿🇦

Johannesburg, Gauteng, South Africa

NorthShore University Health System

🇺🇸

Evanston, Illinois, United States

Sterling Research Group

🇺🇸

Cincinnati, Ohio, United States

The Lindner Research Center

🇺🇸

Cincinnati, Ohio, United States

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