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

Familial Hypercholesterolemia Clinical Trial

— LIBerate-OLE  

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04798430
• Other study ID #: LIB003-007
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: December 3, 2020
• Est. completion date: December 31, 2024

Study information

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

Clinical Trial 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.

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 information / eligibility

• Status: Enrolling by invitation
• Enrollment: 2000
• Est. completion date: December 31, 2024
• Est. primary completion date: October 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Arteriosclerosis
• Cardiovascular Disease With Mention of Arteriosclerosis
• Cardiovascular Diseases
• Elevated Cholesterol
• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• lerodalcibep
PCSK9 inhibitor

Locations

Country	Name	City	State
India	G.B. Pant Institute of Postgraduate Medical Education & Research	New Delhi
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	Afyonkarahisar Health Sciences University	Afyon
Turkey	Ege University Medical School	Izmir	Bornova
United States	Metabolic & Atherosclerosis Research Center (MARC)	Cincinnati	Ohio
United States	Sterling Research Group	Cincinnati	Ohio
United States	The Lindner Research Center	Cincinnati	Ohio
United States	NorthShore University Health System	Evanston	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
LIB Therapeutics LLC	Medpace, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Immunogenicity	Incidence of anti-drug antibodies	72 weeks
Secondary	LDL Cholesterol reduction	Percent decrease in LDL-C from baseline of original study	72 weeks