Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Liposomal siRNA in Subjects With High Cholesterol

Study Overview
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Brief Summary
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This study is a Phase 1, single-center, placebo-controlled, single-blind, first-in-human, single-ascending dose study in male and female subjects with high cholesterol. A maximum of 32 subjects is planned for enrollment in this study.

Official Title
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A Placebo-Controlled, Single-Blind, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PRO-040201 in Male and Female Subjects With Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: PRO-040201
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fasting, stable LDL-C ≥ 160 mg/dL Fasting, stable triglyceride < 400 mg/dL BMI between 22 and 35 kg/m2, inclusive Females must be of non-child bearing potential Males of reproductive potential must agree to practice effective contraception throughout the study and for 3 months following infusion Exclusion Criteria: Clinically significant endocrine, hematologic, renal, hepatic, pulmonary, uncontrolled psychiatric, or neurologic disease Cancer within 5 years prior to screening History of congestive heart failure or chronic heart failure Uncontrolled cardiac arrhythmias History of coronary heart disease Clinically significant abnormal baseline ECG History of additional risk factors for torsades de pointes Hepatitis B, C, or HIV positive Current diagnosis or known history of liver disease A marked baseline prolongation of QT/QTc interval Known history of fibromyalgia, myopathy, myositis, rhabdomyolysis, any unexplained muscle pain, or a creatine phosphokinase (CPK) >3 x upper limit of normal (ULN) at screening Alanine aminotransferase, AST, GGT, or total bilirubin >2 x ULN at screening Serum creatinine > 1.5 mg/dL Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg on 2 occasions during screening Concomitant use of medications that prolongs the QT/QTc interval Treatment with lipid lowering therapy within 30 days prior to screening Use of investigational drug within 3 months prior to screening

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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-040201<br>PRO-040201 with placebo control in each cohort | Drug: PRO-040201<br>* Single dose IV infusion<br>|
| Placebo Comparator: Placebo<br>PRO-040201 with placebo control in each cohort | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of PRO-040201 |  | 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of PRO-040201 in Humans |  | 48 hours | 
| Pharmacodynamics of PRO-040201 in Humans |  | 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholesterol, coronary artery disease