Clinical trial NCT02601560: To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease
Official title: A Phase 2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single- Ascending Doses of MEDI6012 in Subjects With Stable Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Keywords: Coronary Artery Disease
CAD
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-11-10
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a randomized, double-blind (subject/investigator blinded, MedImmune unblinded), placebo-controlled, dose-escalation study to evaluate the safety, PK/PD, and immunogenicity of single IV and SC MEDI6012 doses in adult subjects with stable CAD.


Eligibility criteria: Inclusion Criteria:

* Men and women 40 - 75 years old
* History of Stable CAD
* Currently receiving statin as standard of care

Exclusion Criteria:

* Severe angina pectoris symptoms
* High-risk coronary or carotid artery disease that will likely require surgical or percutaneous intervention during the study period
* Hospitalization for heart failure within 12 months prior to screening
* Uncontrolled Hypertension
* Within 6 months prior to screening, a history of ACS or hospitalization for heart failure
* Clinically significant abnormalities in rhythm, conduction or morphology of ECG
* Subjects with transplanted heart, left ventricular assist device, implanted pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy
* Untreated life-threatening ventricular arrhythmias
* History, within 12 months prior to screening, of myocarditis or restrictive pericarditis, or hemodynamically significant valvular hear disease or aortic disease
* Undergone major surgery with in 3 months prior to screening or has planned major surgery during the study period

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Baseline (Day 1) up to Day 57
measure: Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations
timeFrame: Baseline (Day 1) up to Day 57
measure: Number of Participants With TEAEs Related to Vital Sign Parameters
timeFrame: Baseline (Day 1) up to Day 57
measure: Number of Participants With TEAEs Related to Clinical Laboratory Evaluations
timeFrame: Baseline (Day 1) up to Day 57
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion, 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Secondary outcomes:
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Total Cholesterol
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Free Cholesterol
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Cholesteryl Ester
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for High-Density Lipoprotein Cholesteryl Ester
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Cholesterol
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for High-Density Lipoprotein Unesterified Cholesterol
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Cholesteryl Ester
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Low Density Lipoprotein-Cholesterol (Direct)
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) Post Dose for Apolipoprotein B
timeFrame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
measure: Change From Baseline in Serum Concentration of Pre Beta 1-High Density Lipoprotein at Day 29
timeFrame: Baseline (Day 1) and Day 29
measure: Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57
timeFrame: Baseline (Day 1) and Day 57
measure: Maximum Observed Serum Concentration (Cmax) of MEDI6012
timeFrame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
measure: Time to Reach Concentration Maximum (Tmax) of MEDI6012
timeFrame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
measure: Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012
timeFrame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
measure: Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012
timeFrame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
measure: Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012
timeFrame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
measure: Elimination Half Life (t1/2) of MEDI6012
timeFrame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
measure: Number of Participants With Positive Anti-Drug Antibodies for MEDI6012
timeFrame: Day 1 (pre-dose), 15, 29 and 57
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Falls Church
country: United States
facility: Research Site
state: Virginia
Study officials:
References:
citation: George RT, Abuhatzira L, Stoughton SM, Karathanasis SK, She D, Jin C, Buss NAPS, Bakker-Arkema R, Ongstad EL, Koren M, Hirshberg B. MEDI6012: Recombinant Human Lecithin Cholesterol Acyltransferase, High-Density Lipoprotein, and Low-Density Lipoprotein Receptor-Mediated Reverse Cholesterol Transport. J Am Heart Assoc. 2021 Jul 6;10(13):e014572. doi: 10.1161/JAHA.119.014572. Epub 2021 Jun 14.