Clinical trial NCT04798430: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Cardiovascular Disease With Mention of Arteriosclerosis
Elevated Cholesterol
Familial Hypercholesterolemia
Keywords: lerodalcibep
PCSK9 inhibitor
Lead sponsor: LIB Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2021-03-15
Enrollment: 2000
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label extension trial
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events as assessed by Medical Dictionary for Regulatory Activities as severe, moderate or mild after 48 and 72 weeks
timeFrame: 72 weeks
Secondary outcomes:
measure: Immunogenicity
timeFrame: 72 weeks
measure: LDL Cholesterol reduction
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Cincinnati
country: United States
facility: The Lindner Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Metabolic & Atherosclerosis Research Center (MARC)
state: Ohio
city: New Delhi
country: India
facility: G.B. Pant Institute of Postgraduate Medical Education & Research
city: Jerusalem
country: Israel
facility: Department of Medicine, Hadassah University Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital,
city: Oslo
country: Norway
facility: Lipid Clinic, Oslo University Hospital
city: Johannesburg
country: South Africa
facility: Carbohydrate and Lipid Metabolism Research Unit
state: Gauteng
city: Cape Town
country: South Africa
facility: Division of Lipidology, Department of Medicine University of Cape Town
state: Western Province
city: İzmir
country: Turkey
facility: Ege University Medical School
state: Bornova
city: Afyon
country: Turkey
facility: Afyonkarahisar Health Sciences University
Study officials:
affiliation: LIB Therapeutics
name: David Kallend, MB BCh
role: STUDY_DIRECTOR
References: