A Single Ascending Dose Study Examining the Safety and Pharmacokinetic Profile of Reconstituted High Density Lipoprotein (CSL112) Administered to Patients

Study Overview
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Brief Summary
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Reconstituted high density lipoprotein used in patients with acute coronary syndrome (ACS) may reduce atherosclerotic plaque burden, thereby reducing the risk of recurrent cardiovascular events. This study is a multi-center, randomized, placebo-controlled, single ascending dose study in patients with stable atherothrombotic disease in whom the safety and pharmacokinetic profile of CSL112 will be assessed.

Official Title
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A Phase 2a, Multi-center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of CSL112 in Patients With Stable Atherothrombotic Disease

Conditions
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Stable Atherothrombotic Disease

Intervention / Treatment
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* Biological: CSL112 (reconstituted high density lipoprotein)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 years to 80 years. Subjects must have documented evidence of a history of atherosclerotic coronary artery disease/surgical revascularization. Subjects on a stable medication regimen. Body weight 50 kg or greater at screening. Exclusion Criteria: Moderate/severe heart failure or renal impairment. Uncontrolled hyperglycemia in subjects with type 1 or type 2 diabetes. Receipt of the combination of omeprazole and clopidogrel within 1 month of randomization. Subjects whose medical history, condition or medication regimen may interfere with the evaluation of the safety and tolerability of CSL112 (for example significantly altered electrocardiogram (ECG) waveform, hepatobiliary disease, malignancy, thrombocytopenia, etc.) Known hypersensitivity to the product components

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL112<br> | Biological: CSL112 (reconstituted high density lipoprotein)<br>* Single escalating intravenous doses of CSL112<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Single intravenous doses of normal saline (0.9%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The frequency of study product-related adverse events | 14 days | 
| Clinically significant elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) | Number of subjects with clinically significant elevation of ALT or AST | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of apolipoprotein A-I (apoA-I) | Plasma apoA-I concentration with and without baseline correction | 9 days | 
| Plasma apoA-I area under the curve (AUC) |  | 9 days | 
| Plasma apoA-I Cmax |  | 9 days | 
| Plasma apoA-I Tmax |  | 9 days |