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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Atherosclerosis
• Intervention / Treatment: Drug: ACP-501

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Cardiovascular and Pulmonary Branch (CPB) of NIH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACP-501	Drug: ACP-501; A single dose infusion

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Shamburek RD, Bakker-Arkema R, Shamburek AM, Freeman LA, Amar MJ, Auerbach B, Krause BR, Homan R, Adelman SJ, Collins HL, Sampson M, Wolska A, Remaley AT. Safety and Tolerability of ACP-501, a Recombinant Human Lecithin:Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study. Circ Res. 2016 Jan 8;118(1):73-82. doi: 10.1161/CIRCRESAHA.115.306223. Epub 2015 Dec 1.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 14, 2012
• First Posted (Estimate): March 15, 2012

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Cholesterol; Enzyme replacement therapy; LCAT; High-Density Lipoprotein (HDL); Lecithin Cholesterol Acyl Transferase; rhLCAT; Cholesterol ester; LCAT Deficiency
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis
• Other Study ID Numbers: ACP 501-01; 12-H-0092 (Other Identifier: NIH)