Trial to Evaluate Safety and Tolerability of ALN-PCS02 in Subjects With Elevated LDL-Cholesterol (LDL-C)

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of a single dose of ALN-PCS02 in subjects with Elevated LDL-Cholesterol (LDL-C).

Official Title
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A Phase 1, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of ALN-PCS02 in Subjects With Elevated LDL-Cholesterol (LDL-C)

Conditions
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Elevated LDL-Cholesterol (LDL-C)

Intervention / Treatment
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* Drug: ALN-PCS02
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elevated LDL-C of >3.0 mmol/L and <5.7 mmol/L Fasting triglyceride concentration ≤2.8 mmol/L Body weight >60.0 kg; body mass index (BMI) between 19.00 kg/m2 and <35.00 kg/m2 Adequate blood counts, liver and renal function May not received any lipid lowering drug/agent within the 30 days prior to the screening Non-smokers for at least 3 months Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use an adequate method of birth control Males agree to use appropriate contraception Willing and able to comply with protocol-required visit schedule and visit requirements and provide written informed consent Exclusion Criteria: Known hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection Multiple drug allergies or know sensitivity to oligonucleotide History of drug abuse and/or alcohol abuse Receiving an investigational agent within 3 months prior to study drug administration Subjects with safety laboratory test results deemed clinical significant by the Investigator; Received prescription drugs within 4 weeks of first dosing Subjects who have donated more than 500 mL of blood within the 3 months prior to ALN-PCS02 or placebo administration; Received megadose vitamin therapy or dietary supplements within 4 weeks prior to screening Subjects who have used prescription drugs within 4 weeks of first dosing Considered unfit for the study by the Principal Investigator Employee or family member of the sponsor or the clinical study site personnel

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALN-PCS02<br> | Drug: ALN-PCS02<br>* Dose levels between 15 and 400 μg/kg by intravenous (IV) infusion<br>|
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br> | Drug: Sterile Normal Saline (0.9% NaCl)<br>* Calculated volume to match active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation. |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ALN-PCS02 (Cmax, tmax, t1/2, AUC0-last, CL). |  | Up to 180 days | 
| Effect of ALN-PCS02 on Circulating PCSK9 Levels (Determination of % Lowering of PCSK9 to pretreatment/Baseline PCSK9 Level). |  | Up to 28 days | 
| Effect of ALN-PCS02 on Circulating LDL-c Levels (Determination of % Lowering of LDL-c to pretreatment/Baseline LDL-c Level). |  | Up to 28 days |