Clinical trial NCT01554800: Effect of ACP-501 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Subjects With Coronary Artery Disease
Official title: An Intravenous, Open-label, Single-dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of rhLCAT in Subjects With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coronary Artery Disease
Atherosclerosis
Keywords: Lecithin Cholesterol Acyl Transferase
LCAT
rhLCAT
Enzyme replacement therapy
High-Density Lipoprotein (HDL)
Cholesterol
Cholesterol ester
LCAT Deficiency
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-03-15
Enrollment: 16
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Summary of Participants Experience with Safety and Tolerability
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Pharmacokinetic profile
timeFrame: Hours 0, 1, 6, 12, 24, 48, 72, 96, 168
measure: Change in High-Density Lipoprotein-Cholesterol (HDL-C) value following a single dose
timeFrame: Hours 0, 1, 6, 12, 24, 48, 72, 96, 168
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Cardiovascular and Pulmonary Branch (CPB) of NIH
state: Maryland
Study officials:
References:
citation: 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.