Lerodalcibep for High Cholesterol

(LIBerate-OLE Trial)

Enrolling by invitation at 13 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: LIB Therapeutics LLC

Must be taking: Lipid-lowering therapy

Must not be taking: PCSK9 mAbs, mipomersen

Disqualifiers: Unstable disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and effectiveness of lerodalcibep for individuals with high cholesterol at risk for heart disease. Participants will receive a monthly injection to assess its management of cholesterol levels over time. Those who participated in a related study and are on stable cholesterol-lowering medications might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires you to stay on your current lipid-lowering medications, like statins or ezetimibe, as long as they are not on the prohibited list. You should not be using certain other medications like PCSK9 mAbs or mipomersen.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that lerodalcibep is generally well-tolerated. In earlier studies, patients taking lerodalcibep experienced significant reductions in LDL cholesterol levels without major safety concerns. Its safety profile was similar to other treatments in its category, indicating no unexpected increase in side effects. Long-term studies have shown that it remains effective over time, with serious side effects being rare.

For those considering joining a clinical trial for lerodalcibep, these studies suggest it is safe for most people. However, discussing any concerns with a doctor is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high cholesterol, which often include statins like atorvastatin and rosuvastatin, Lerodalcibep is administered through a subcutaneous injection of 300 mg once a month. This method can be more convenient for patients who struggle with daily pill regimens. Importantly, Lerodalcibep works by a novel mechanism that targets and inhibits the PCSK9 protein, which plays a crucial role in cholesterol regulation. Researchers are excited because this approach not only offers a new option for lowering cholesterol but could also provide benefits for patients who are resistant to or cannot tolerate traditional statin therapies.

What evidence suggests that lerodalcibep might be an effective treatment for high cholesterol?

Research has shown that lerodalcibep, the investigational treatment in this trial, effectively lowers LDL cholesterol, often called "bad" cholesterol, which can lead to heart disease. One study found that lerodalcibep reduced LDL cholesterol levels by about 58.61% compared to a placebo. In another study, about 86.2% of patients experienced at least a 50% drop in their LDL cholesterol levels. Additionally, around 69.6% of patients achieved their cholesterol goals with this treatment. These promising results suggest that lerodalcibep can significantly lower cholesterol levels in people at risk for heart disease. ^{1 2 6 7 8}

Who Is on the Research Team?

David Kallend, MB BCh

Principal Investigator

LIB Therapeutics

Are You a Good Fit for This Trial?

This trial is for patients with cardiovascular disease or at high risk, including those with genetic cholesterol disorders (HoFH and HeFH), who've completed a prior Phase 3 study without serious issues from the drug. They must be on stable cholesterol-lowering meds and diet, use effective birth control if applicable, and commit to all study visits.

Inclusion Criteria

Provision of written and signed informed consent prior to any study-specific procedure

Successful completion 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

Patient is considered by the Investigator to be otherwise healthy

Exclusion Criteria

Not available for protocol-required study visits or procedures, to the best of the patient's and Investigator's knowledge

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants receive monthly subcutaneous injections of LIB003 300 mg for long-term efficacy and safety assessment

72 weeks

Clinic visits every 4 weeks for the first 12 weeks, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lerodalcibep

Trial Overview The trial tests long-term safety and effectiveness of lerodalcibep injections every month for up to 72 weeks in lowering 'bad' cholesterol levels. Participants have already finished earlier phases of the study and are continuing their regular cholesterol treatments alongside this new therapy.

How Is the Trial Designed?

Group I: LIB003 (lerodalcibep) Experimental Treatment 1 Intervention

300 mg monthly (Q4W) by subcutaneous injection

Who Is Running the Clinical Trial?

LIB Therapeutics LLC

Lead Sponsor

Trials

11

Recruited

4,900+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

In a study of high-risk patients switched from simvastatin therapy, the combination of ezetimibe/simvastatin led to significantly greater reductions in LDL cholesterol (37 mg/dL) compared to rosuvastatin (25 mg/dL) and atorvastatin (26 mg/dL).

All treatment regimens improved other lipid parameters, such as total cholesterol and triglycerides, with no significant differences in adverse events among the different therapies, indicating a similar safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. Furman, A., Meier, JL., Malmstrom, RA., et al.[2018]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2820248

Efficacy and Safety of Lerodalcibep in Patients With or at ... Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10590131/

Long-term efficacy and safety of lerodalcibep in heterozygous ... A reduction in LDL-C of ≥50% was achieved in 275 subjects (86.2%) with lerodalcibep, and ESC LDL-C targets were achieved in 222 (69.6%) subjects (Figure 3).

3. jacc.org jacc.org/doi/full/10.1016/S0735-1097(24)03694-5

LONG-TERM EFFICACY AND SAFETY OF ... Lerodalcibep, a novel small binding protein inhibitor of circulating PCSK9, reduced placebo-adjusted LDL-cholesterol (LDL-C) by a mean(SE) of 58.61(3.25)% ...

4. tctmd.com tctmd.com/news/now-published-liberate-hr-lerodalcibep-lowers-ldl-more-sharply-placebo-over-1-year

LIBerate-HR: Lerodalcibep Lowers LDL More Sharply ... At week 52, those in the lerodalcibep group had a 56.19% greater reduction in LDL cholesterol compared with placebo (-56.33 vs -0.14%; P < 0.001) ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39870096/

Lerodalcibep and evolocumab for the treatment of ... Mean LDL cholesterol reduction by ITT analysis at week 24 was -4·9% (SE 3·5) on lerodalcibep compared with -10·3% (3·5) on evolocumab; the mean ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04806893

NCT04806893 | Study of Long-Term Efficacy and Safety ... Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial. JAMA Cardiol. 2024 Sep 1;9(9): ...

7. jacc.org jacc.org/doi/10.1016/S0735-1097%2824%2903694-5

LONG-TERM EFFICACY AND SAFETY OF ... Lerodalcibep dosed monthly significantly and persistently reduced LDL-C, apo-B and Lp(a) in HeFH subjects with no attenuation and with a safety profile similar ...

8. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(24)00973-0/fulltext

Randomized, open-label, study comparing efficacy and ... Randomized, open-label, study comparing efficacy and safety of lerodalcibep to inclisiran in patients with CVD or at high risk for CVD requiring additional LDL- ...