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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

Official Title
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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

Conditions
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Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: lerodalcibep
* Drug: evolocumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: open label, randomized, cross-over
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIB003 (lerodalcibep)<br>300 mg SC Q4W | Drug: lerodalcibep<br>* PCSK9 inhibitor<br>* Other names: LIB003;|
| Active Comparator: evolocumab<br>420 mg SC Q4W | Drug: evolocumab<br>* PCSK9 inhibitor<br>* Other names: Repatha;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL cholesterol, PCSK9 inhibition