Effect of ACP-501 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Subjects With Coronary Artery Disease

Study Overview
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Brief Summary
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This study is a phase 1, intravenous, open-label, single-dose escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ACP-501 (recombinant human Lecithin Cholesterol Acyl Transferase (rhLCAT)) in subjects with coronary artery disease (CAD). Four cohorts consisting of 4 subjects each will receive one dose of ACP-501. The dose will be escalated by cohort.

Detailed Description
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After signing informed consent, subjects entered into the trial will be followed for up to 8 weeks which includes: up to 4 weeks screening, entry criteria assessments on Day 0 and single-dose IV infusion on Day 1, and 4 weeks of follow-up.

Official Title
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An Intravenous, Open-label, Single-dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of rhLCAT in Subjects With Coronary Artery Disease

Conditions
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Coronary Artery Disease, Atherosclerosis

Intervention / Treatment
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* Drug: ACP-501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A history of stable documented CAD Currently non-smoking males and females ages 30 to 85 years inclusive. o Female subjects of child-bearing potential (neither pregnant nor breast-feeding) must be using adequate birth control during study conduct. Chronic concomitant medications must be stable for at least 2 months prior to screening HDL-C < 50 mg/dL for men and < 55 mg/dL for women Body Mass Index (BMI) of approximately 18 to 35 kg/m^2; and a total body weight >= 50 kg (110 lbs) and <= 110 kg (approximately 242 lbs) Exclusion Criteria: Myocardial infarction, stroke, or coronary intervention/revascularization procedure within 6 months prior to dosing. Chronic heart failure (> New York Heart Association (NYHA) Functional Classification II). Ventricular tachyarrhythmias. Uncontrolled Type 2 (HbA1c > 8.5%) or Type 1 diabetes mellitus. History of febrile illness within 5 days prior to dosing. History of regular alcohol consumption exceeding 10 drinks per week. 12-lead ECG demonstrating QTc > 500 msec at screening. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACP-501<br> | Drug: ACP-501<br>* A single dose infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Participants Experience with Safety and Tolerability | Safety and tolerability of a single dose of ACP-501 as determined by adverse event reporting, clinical laboratory results, vital signs, physical examination, and electrocardiograms (ECGs). | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile |  | Hours 0, 1, 6, 12, 24, 48, 72, 96, 168 | 
| Change in High-Density Lipoprotein-Cholesterol (HDL-C) value following a single dose |  | Hours 0, 1, 6, 12, 24, 48, 72, 96, 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lecithin Cholesterol Acyl Transferase, LCAT, rhLCAT, Enzyme replacement therapy, High-Density Lipoprotein (HDL), Cholesterol, Cholesterol ester, LCAT Deficiency