Study of Long-Term Efficacy and Safety of LIB003 in CVD or High Risk for CVD Patients Needing Further LDL-C Reduction (LIBerate-HR)
Primary Purpose
Cardiovascular Risk Factor, Cardiovascular Diseases, Cardiovascular Stroke
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
lerodalcibep
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cardiovascular Risk Factor focused on measuring lerodalcibep, PCSK9 inhibitor
Eligibility Criteria
Inclusion Criteria:
- Provision of written and signed informed consent prior to any study-specific procedure;
- Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2;
- History of CVD, (including cerebrovascular or peripheral arterial disease) or very-high risk for CVD as defined in the 2019 ESC/EAS Guidelines or
- High risk for CVD as defined in the 2019 ESC/EAS Guidelines
- At Screening or post Washout/Stabilization, LDL-C ≥70 mg/dL and TG ≤400 mg/dL while on stable lipid-lowering oral drug therapy (i.e., maximally tolerated statin with or without ezetimibe); Patients unable to tolerate approved doses of a statin may take lower than approved doses and dose less frequently than daily as long as the dose and dosing frequency is consistent; Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, may also participate;
- Stable diet and lipid-lowering oral therapies (such as statins, ezetimibe, bile-acid sequestrants, OM-3 compounds, fenofibrate, bezafibrate, nicotinic acid, and bempedoic acid) or combinations thereof for at least 4 weeks
- Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥4 weeks after the last dose; for those on 300 mg or 420 mg Q4W (≤31 days) the washout period is ≥8 weeks following last dose;
- Females of childbearing potential must be using a highly effective form of birth control if sexually active and have a negative urine pregnancy test at the last Screening Visit;
Exclusion Criteria:
- Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of screening, apheresis within 2 months prior to randomization; received other investigational agent(s) such as PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months of the Screening Visit;
- Documented history of HoFH defined clinically or genetically
- History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator
- Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit;
- Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2
- Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × the ULN as determined by central laboratory analysis at screening
- Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism
- Uncontrolled Type 1 or Type 2 DM, defined as FBS ≥200 mg/dL or HbA1C ≥9%;
- Uncontrolled serious cardiac arrhythmia, MI, unstable angina, PCI, CABG, placement of implantable cardioverter defibrillator or biventricular pacemaker, aortic valve surgery, or stroke within 3 months prior to the Screening Visit;
- Planned cardiac surgery or revascularization;
- New York Heart Association class III-IV heart failure
Sites / Locations
- Sterling Research Group
- The Lindner Research Center
- Metabolic & Atherosclerosis Research Center (MARC)
- G.B. Pant Institute of Postgraduate Medical Education & Research
- Department of Medicine, Hadassah University Hospital
- Rabin Medical Center, Beilinson Hospital,
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LIB003 (lerodalcibep)
Placebo
Arm Description
300 mg subcutaneously monthly (Q4W)
matching placebo subcutaneously monthly (Q4W)
Outcomes
Primary Outcome Measures
LDL-C change compared to placebo
Percent change in LS mean from baseline compared to placebo in LDL-C level
mean LDL-C change at week 50 and 52
Percent change in LS mean from baseline compared to placebo in LDL-C level at Weeks 50 and 52
Secondary Outcome Measures
Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 52 weeks
Evaluation of Adverse Events based on MedRA based on ITT population
Change in Free PCSK9
Percent change in LS mean from baseline compared to placebo in free PCSK9
Percentage of patients achieving 2019 ESC/EAS LDL-C goals
To assess the effects of LIB003 on the percentage of patients achieving an LDL-C <40 mg/dL, 55 mg/dL, <70 mg/dL, and 100 mg/dL
Full Information
NCT ID
NCT04806893
First Posted
March 16, 2021
Last Updated
November 3, 2022
Sponsor
LIB Therapeutics LLC
Collaborators
Medpace, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04806893
Brief Title
Study of Long-Term Efficacy and Safety of LIB003 in CVD or High Risk for CVD Patients Needing Further LDL-C Reduction
Acronym
LIBerate-HR
Official Title
Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Patients With Cardiovascular Disease, or at High Risk for Cardiovascular Disease, on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 22, 2021 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LIB Therapeutics LLC
Collaborators
Medpace, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to assess LDL-C reductions at Week 52 with monthly (Q4W [≤31 days]) dosing of LIB003 (lerodalcibep) 300 mg administered subcutaneously (SC) compared to placebo in patients with CVD, or at high risk for CVD, on a stable diet and oral LDL-C lowering drug therapy
Detailed Description
Randomized, double-blind, placebo-controlled, Phase 3 study of 52 weeks duration.
Patients who fulfill the inclusion and exclusion criteria will be enrolled at up to 65 sites in the United States, Canada, Europe, South Africa, Asia, Australasia, and the Middle East. Patients will be randomized in a 2:1 ratio to LIB003 or placebo. The total study duration will be up to 63 weeks which includes up to a Screening Period and 52 weeks of study drug treatment. Following randomization patients will be dosed and seen in the clinic Q4W (≤31 days).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Risk Factor, Cardiovascular Diseases, Cardiovascular Stroke, Hypercholesterolemia
Keywords
lerodalcibep, PCSK9 inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Placebo-controlled, randomized 2:1 to Active or placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
participants, study staff, investigator and sponsor blinded to treatment and lipid levels
Allocation
Randomized
Enrollment
900 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LIB003 (lerodalcibep)
Arm Type
Experimental
Arm Description
300 mg subcutaneously monthly (Q4W)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
matching placebo subcutaneously monthly (Q4W)
Intervention Type
Drug
Intervention Name(s)
lerodalcibep
Other Intervention Name(s)
LIB003
Intervention Description
300 mg subcutaneous injection every month (Q4W)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
matching subcutaneous injection every month (Q4W)
Primary Outcome Measure Information:
Title
LDL-C change compared to placebo
Description
Percent change in LS mean from baseline compared to placebo in LDL-C level
Time Frame
52 weeks
Title
mean LDL-C change at week 50 and 52
Description
Percent change in LS mean from baseline compared to placebo in LDL-C level at Weeks 50 and 52
Time Frame
50 and 52 weeks
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 52 weeks
Description
Evaluation of Adverse Events based on MedRA based on ITT population
Time Frame
52 weeks
Title
Change in Free PCSK9
Description
Percent change in LS mean from baseline compared to placebo in free PCSK9
Time Frame
52 weeks
Title
Percentage of patients achieving 2019 ESC/EAS LDL-C goals
Description
To assess the effects of LIB003 on the percentage of patients achieving an LDL-C <40 mg/dL, 55 mg/dL, <70 mg/dL, and 100 mg/dL
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of written and signed informed consent prior to any study-specific procedure;
Weight of ≥40 kg (88 lb) and body mass index (BMI) ≥17 and ≤42 kg/m2;
History of CVD, (including cerebrovascular or peripheral arterial disease) or very-high risk for CVD as defined in the 2019 ESC/EAS Guidelines or
High risk for CVD as defined in the 2019 ESC/EAS Guidelines
At Screening or post Washout/Stabilization, LDL-C ≥70 mg/dL and TG ≤400 mg/dL while on stable lipid-lowering oral drug therapy (i.e., maximally tolerated statin with or without ezetimibe); Patients unable to tolerate approved doses of a statin may take lower than approved doses and dose less frequently than daily as long as the dose and dosing frequency is consistent; Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, may also participate;
Stable diet and lipid-lowering oral therapies (such as statins, ezetimibe, bile-acid sequestrants, OM-3 compounds, fenofibrate, bezafibrate, nicotinic acid, and bempedoic acid) or combinations thereof for at least 4 weeks
Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥4 weeks after the last dose; for those on 300 mg or 420 mg Q4W (≤31 days) the washout period is ≥8 weeks following last dose;
Females of childbearing potential must be using a highly effective form of birth control if sexually active and have a negative urine pregnancy test at the last Screening Visit;
Exclusion Criteria:
Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of screening, apheresis within 2 months prior to randomization; received other investigational agent(s) such as PCSK9 or Lp(a) siRNA or locked nucleic acid-reducing agents within 12 months of the Screening Visit;
Documented history of HoFH defined clinically or genetically
History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator
Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit;
Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2
Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × the ULN as determined by central laboratory analysis at screening
Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism
Uncontrolled Type 1 or Type 2 DM, defined as FBS ≥200 mg/dL or HbA1C ≥9%;
Uncontrolled serious cardiac arrhythmia, MI, unstable angina, PCI, CABG, placement of implantable cardioverter defibrillator or biventricular pacemaker, aortic valve surgery, or stroke within 3 months prior to the Screening Visit;
Planned cardiac surgery or revascularization;
New York Heart Association class III-IV heart failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evan A Stein, MD PhD
Organizational Affiliation
LIB Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Sterling Research Group
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
The Lindner Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Metabolic & Atherosclerosis Research Center (MARC)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45227
Country
United States
Facility Name
G.B. Pant Institute of Postgraduate Medical Education & Research
City
New Delhi
ZIP/Postal Code
110002
Country
India
Facility Name
Department of Medicine, Hadassah University Hospital
City
Jerusalem
ZIP/Postal Code
12000
Country
Israel
Facility Name
Rabin Medical Center, Beilinson Hospital,
City
Petah Tikva
ZIP/Postal Code
49100
Country
Israel
12. IPD Sharing Statement
Learn more about this trial
Study of Long-Term Efficacy and Safety of LIB003 in CVD or High Risk for CVD Patients Needing Further LDL-C Reduction
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