To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease
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
1 other identifier
interventional
48
1 country
8
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 coronary-artery-disease
Started Dec 2015
Shorter than P25 for phase_2 coronary-artery-disease
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2015
CompletedFirst Posted
Study publicly available on registry
November 10, 2015
CompletedStudy Start
First participant enrolled
December 3, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 20, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 3, 2016
CompletedResults Posted
Study results publicly available
March 19, 2018
CompletedMarch 19, 2018
March 1, 2018
9 months
November 9, 2015
December 8, 2017
March 16, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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 (Day 1) up to Day 57
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations
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.
Baseline (Day 1) up to Day 57
Number of Participants With TEAEs Related to Vital Sign Parameters
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.
Baseline (Day 1) up to Day 57
Number of Participants With TEAEs Related to Clinical Laboratory Evaluations
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.
Baseline (Day 1) up to Day 57
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)
The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of 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)
Secondary Outcomes (19)
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)
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)
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)
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)
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)
- +14 more secondary outcomes
Study Arms (8)
MEDI6012 24 mg IV
EXPERIMENTALParticipants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV
EXPERIMENTALParticipants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV
EXPERIMENTALParticipants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV
EXPERIMENTALParticipants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 80 mg SC
EXPERIMENTALParticipants received a single SC dose of 80 mg MEDI6012 on Day 1.
Placebo Intravenous (IV)
PLACEBO COMPARATORParticipants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 600 mg SC
EXPERIMENTALParticipants received a single SC dose of 600 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)
PLACEBO COMPARATORParticipants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
Interventions
Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
Eligibility Criteria
You may qualify if:
- Men and women 40 - 75 years old
- History of Stable CAD
- Currently receiving statin as standard of care
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MedImmune LLClead
Study Sites (8)
Research Site
Anniston, Alabama, 36207, United States
Research Site
Jacksonville, Florida, 32216, United States
Research Site
Port Orange, Florida, 32127, United States
Research Site
Durham, North Carolina, 27710, United States
Research Site
Raleigh, North Carolina, 27612, United States
Research Site
Cincinnati, Ohio, 45227, United States
Research Site
San Antonio, Texas, 78229, United States
Research Site
Falls Church, Virginia, 22042, United States
Related Publications (1)
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.
PMID: 34121413DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Richard George, MD, Director, Clinical Development
- Organization
- MedImmune, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2015
First Posted
November 10, 2015
Study Start
December 3, 2015
Primary Completion
August 20, 2016
Study Completion
November 3, 2016
Last Updated
March 19, 2018
Results First Posted
March 19, 2018
Record last verified: 2018-03