To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease

Phase 2

Completed

• Conditions: Coronary Artery Disease
• Interventions: Biological: Placebo IV; Biological: MEDI6012; Biological: Placebo SC

• Registration Number: NCT02601560
• Lead Sponsor: MedImmune LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-09
• Study First Submitted QC: 2015-11-09
• Study First Posted: 2015-11-10
• Study Start: 2015-12-03
• Primary Completion: 2016-08-20
• Study Completion: 2016-11-03
• Disposition First Submitted: 2017-08-01
• Disposition First Submitted QC: 2017-08-16
• Disposition First Posted: 2017-08-18
• Results First Submitted: 2017-12-08
• Status Verified: 2018-03
• Results First Submitted QC: 2018-03-16
• Last Update Submitted: 2018-03-16
• Results First Posted: 2018-03-19
• Last Update Posted: 2018-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo Intravenous (IV)	Placebo IV	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 mg IV	MEDI6012	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	MEDI6012	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	MEDI6012	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Placebo SC	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg IV	MEDI6012	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 80 mg SC	MEDI6012	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	MEDI6012	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants With TEAEs Related to Vital Sign Parameters	Baseline (Day 1) up to Day 57	TEAEs observed in participants with clinically significant vital signs abnormalities were assessed. Vital signs parameters included blood pressure, respiration rate, pulse, pulse oximetry, and body temperature.
Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	Baseline (Day 1) up to Day 57	An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	Baseline (Day 1) up to Day 57	TEAEs observed in participants with clinically significant ECG abnormalities were assessed. TEAEs are the events between first dose of study drug and up to 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	Baseline (Day 1) up to Day 57	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are the events between first dose of study drug and up to 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of HDL-C.

Secondary Outcome Measures

Name	Time	Method
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Low Density Lipoprotein-Cholesterol (Direct)	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of low density lipoprotein cholesterol (direct).
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Cholesteryl Ester	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)	The AUC(0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of cholesteryl ester.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for High-Density Lipoprotein Unesterified Cholesterol	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of high density lipoprotein unesterified cholesterol.
Change From Baseline in Serum Concentration of Pre Beta 1-High Density Lipoprotein at Day 29	Baseline (Day 1) and Day 29	The change from baseline in serum concentration of pre beta 1-high density lipoprotein was estimated.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Total Cholesterol	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of total cholesterol.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Free Cholesterol	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of free cholesterol.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for High-Density Lipoprotein Cholesteryl Ester	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of high density lipoprotein cholesteryl ester.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) Post Dose for Apolipoprotein B	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of apolipoprotein B.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Cholesterol	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)	The AUC(0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein cholesterol.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Cholesteryl Ester	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein cholesteryl ester.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol	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)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein unesterified cholesterol.
Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57	Baseline (Day 1) and Day 57	The change from baseline in serum concentration of lecithin-cholesterol acyltransferase was estimated.
Maximum Observed Serum Concentration (Cmax) of MEDI6012	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)	The first occurrence of the maximum observed plasma concentration of MEDI6012 determined directly from the raw concentration time data.
Time to Reach Concentration Maximum (Tmax) of MEDI6012	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)	The time at which Cmax of MEDI6012 was observed determined directly from raw concentration time data.
Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	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)	The area under the concentration-time curve from 0 to 168 hrs of MEDI6012.
Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	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)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUC \[0-last\]) of MEDI6012.
Elimination Half Life (t1/2) of MEDI6012	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)	The t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	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)	The area under the concentration-time curve to infinite time of MEDI6012.
Number of Participants With Positive Anti-Drug Antibodies for MEDI6012	Day 1 (pre-dose), 15, 29 and 57	Participants were tested for immunogenicity to MEDI6012. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of MEDI6012 to its target.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Falls Church, Virginia, United States