Cross-Over Study to Compare the Pharmacokinetics and Pharmacodynamics of LIB003 Process 1 and Process 2 Drug Product

Study Overview
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Brief Summary
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To compare the pharmacokinetics (PK), and pharmacodynamics (PD) of single subcutaneous (SC) doses of 300 mg LIB003 Process 1 (P1) and Process 2 (P2) drug product in subjects with or without statin therapy

Detailed Description
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Comparison of the pharmacokinetics (PK), and pharmacodynamics (free PCSK9 and LDL-C) of single subcutaneous (SC) doses of 300 mg of both LIB003 drug product manufactured by Process 1 (P1) and Process 2 (P2) in subjects with or without statin therapy

Official Title
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Cross-Over Study to Compare the Pharmacokinetics and Pharmacodynamics of LIB003 Process 1 and Process 2 Drug Product in Subjects With or Without Statin Therapy

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: lerodalcibep


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written and signed informed consent prior to any study-specific procedure LDL-C 70 mg/dL or above on stable diet alone or diet plus statin Weight of 40 kg (88 lb) and body mass index (BMI) between 17 and 42 kg/m2 Females of childbearing potential must be using a highly effective form of birth control Male subjects will either be surgically sterile or agree, or partner agrees, to use highly effective form of birth control Exclusion Criteria: Fasting triglyceride >400 mg/dL excluded lipid lowering medication severe renal impairment (eGFR <30 ml/min) fasting glucose >200 mg/dL plus HbA1c >9% hepatic transaminases >2.5 x ULN for laboratory History of any prior or active clinical condition or acute and/or unstable systemic disease compromising subject inclusion, at the discretion of the Investigator, NYHA class III-IV heart failure or last documented left ventricular EF <30% Any severe or clinically significant advert event, laboratory abnormality, intercurrent illness, or other medical condition which indicates to the Investigator that continued participation is not in the best interest of the subject

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: assignment to initial treatment group with cross over to alternate treatment group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIB003 (lerodalcibep) Process 1<br>300 mg LIB003 Process 1 drug product administered SC | Drug: lerodalcibep<br>* 300 mg of each drug given SC as single dose<br>* Other names: LIB003;|
| Active Comparator: LIB003 (lerodalcibep) Process 2<br>300 mg LIB003 Process 2 drug product administered SC | Drug: lerodalcibep<br>* 300 mg of each drug given SC as single dose<br>* Other names: LIB003;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacodynamics | comparison of free PCSK9 reductions from baseline between P1 and P2 | 4 weeks | 
| Cmax pharmacokinetics | comparison of serum lerodalcibep Cmax between P1 and P2 | 4 weeks | 
| AUC 0-last pharmacokinetics | comparison of serum lerodalcibep AUC 0-last between P1 and P2 | 4 weeks | 
| T-Half pharmacokinetics | comparison of serum lerodalcibep T-HALF between P1 and P2 | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| comparison of LDL-C | comparison of serum LDL-C reductions from baseline to week 4 between P1 and P2 | 4 weeks |