A Phase 1 Study of an Investigational Drug, ALN-PCSSC, in Subjects With Elevated Low Density Lipoprotein Cholesterol (LDL-C)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-PCSSC in subjects with elevated LDL-C.

Official Title
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A Phase 1, Randomized, Single Blind, Placebo Controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN PCSSC in Subjects With Elevated Low Density Lipoprotein Cholesterol

Conditions
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Hypercholesterolemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate complete blood counts, liver and renal function Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization Male subjects agree to use appropriate contraception Willing to provide written informed consent and willing to comply with study requirements. Non-smokers and non-nicotine users for at least 90 days before screening On stable statin co-medication [for designated multiple dose cohorts only] Exclusion Criteria: Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study History of multiple drug allergies or intolerance to subcutaneous injection Received any medication or nutraceutical to alter serum lipids within 30 days before screening (non-statin cohorts only)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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-PCSSC<br> | Drug: ALN-PCSSC<br>* Single or multiple doses of ALN-PCSSC by subcutaneous (sc) injection<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 safety of ALN-PCSSC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation |  | Part 1 (SAD phase): up to 180 days post dose; Part 2 (MD) phase: up to 180 days post final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetics (PK) of ALN-PCSSC (Cmax, tmax, AUC, t1/2) |  | Part 1 (SAD) phase: predose, 0.5,1,2,4,6,8,12,24,48,72,96 hours; 7, 14, 21, 28, 42, 56 days post-dose; Part 2 (MD) phase: predose, 0.5,1,2,4,6,8,12,24,48,72,96 hours; 7, 14, 21, 28, 29, 35, 42, 56, 84 days post-dose | 
| The effect of ALN-PCSSC on serum levels of LDL-C |  | Through the sooner of final follow up visit or 180 days post final dose | 
| The effect of ALN-PCSSC on plasma levels of PCSK9 |  | Through the sooner of final follow up visit or 180 days post final dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL-C, RNAi therapeutic