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

Tracking Information

• First Submitted Date: March 9, 2021
• First Posted Date: March 15, 2021
• Last Update Posted Date: March 29, 2023
• Actual Study Start Date: December 3, 2020
• Estimated Primary Completion Date: October 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 11, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

Condition

• Cardiovascular Disease With Mention of Arteriosclerosis
• Elevated Cholesterol
• Familial Hypercholesterolemia

Intervention

Drug: lerodalcibep

PCSK9 inhibitor

Other Name: LIB003

Study Arms

Experimental: LIB003 (lerodalcibep)

300 mg monthly (Q4W) by subcutaneous injection

Intervention: Drug: lerodalcibep

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: March 11, 2021): 2000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: October 30, 2024 (Final data collection date for primary outcome measure)

Eligibility 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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India, Israel, Norway, South Africa, Turkey, United States

Administrative Information

• NCT Number: NCT04798430
• Other Study ID Numbers: LIB003-007
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: LIB Therapeutics LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: LIB Therapeutics LLC
• Original Study Sponsor: Same as current
• Collaborators: Medpace, Inc.

Investigators

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

• PRS Account: LIB Therapeutics LLC
• Verification Date: March 2023