Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in HoFH

Randomized, Open-Label, Cross-Over, Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in Homozygous Familial Hypercholesterolemia Patients on Stable Lipid-Lowering Therapy

To compare the safety, tolerability and LDL-C response after 24 Weeks of monthly (every 4 weeks [Q4W]) subcutaneous (SC) dosing of LIB003 300 mg with monthly (Q4W) SC dosing of 420 mg evolocumab (Repatha®) in patients with HoFH on stable diet and oral LDL-C-lowering drug therapy

Study Overview

• Status: Completed
• Conditions: Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: lerodalcibep; Drug: evolocumab

Detailed Description

Patients with verified HoFH on stable and continuing doses of oral lipid lowering therapy will be randomized to either evolocumab 420 mg Q4W or LIB003 300 mg Q4W for 24 weeks (Period A). At Week 24, subjects will be crossed over to LIB003 if they were on evolocumab and vice versa for the next 24 weeks (Period B).

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Ahmedabad, India
    • CIMS Hospital Pvt. Ltd
  • New Delhi, India, 110002
    • G.B. Pant Institute of Postgraduate Medical Education & Research
  • NCT
    • Delhi, NCT, India
      • VMMC & Safdarjung Hospital
• 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, 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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HoFH diagnosed clinically and confirmed by genotyping
• Weight of >30 kg and body mass index (BMI) >17 and <40 kg/m2
• stable diet and lipid-lowering oral therapies for at least 4 weeks

Exclusion Criteria:

• mipomersen within 6 months of screening;
• LDL or plasma apheresis <2 months prior to randomization
• history of non-response to PCSK9 mAb or presence of receptor negative/null LDLR activity expected to result in non-response to PCSK9 inhibition
• prior or active clinical condition or acute and/or unstable systemic disease compromising subject inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LIB003 (lerodalcibep); 300 mg SC Q4W	Drug: lerodalcibep; PCSK9 inhibitor; Other Names: LIB003
Active Comparator: evolocumab; 420 mg SC Q4W	Drug: evolocumab; PCSK9 inhibitor; Other Names: Repatha

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent reduction in Low Density Lipoprotein Cholesterol (LDL-C) at week 24	Change in serum LDL-C from baseline after 24 weeks	baseline to 24 weeks on each treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence and severity of treatment emergent adverse events (TEAEs)	safety and tolerability will be based on the incidence and severity of treatment emergent adverse events	baseline to 24 weeks on each treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent reduction in lipoprotein (a) [Lp(a)] at week 24	Change in serum Lp(a) from baseline after 24 weeks	baseline to 24 weeks on each treatment
Percent reduction in apolipoprotein B (Apo B) at week 24	Change in serum Apo B from baseline after 24 weeks	baseline to 24 weeks on each treatment
Presence of anti LIB003 antibodies (ADAs)	Measurement of ADAs at baseline and various intervals	baseline to 24 weeks

Collaborators and Investigators

• Sponsor: LIB Therapeutics LLC
• Investigators: Study Director: Evan A Stein, MD PhD, LIB Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2019
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: LDL cholesterol; PCSK9 inhibition
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: LIB003-003

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