A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of MEDI5884 in Adults With Stable Coronary Heart Disease

Study Overview
=================
Brief Summary
-----------------
A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of MEDI5884 in Adults With Stable Coronary Heart Disease.

Detailed Description
-----------------
A Randomized, Double-blind, Placebo-controlled, Parallel-designed Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of MEDI5884 in Participants with Stable Coronary Heart Disease.

Official Title
-----------------
A Phase 2a Randomized, Double-blind, Placebo-controlled, Parallel-designed Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of MEDI5884 in Subjects With Stable Coronary Heart Disease

Conditions
-----------------
Stable Coronary Heart Disease

Intervention / Treatment
-----------------
* Drug: MEDI5884
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of stable coronary heart disease prior to screening Currently receiving high intensity statin(s) Exclusion Criteria: Unstable cardiovascular conditions Any planned arterial revascularizations Fasting Laboratory values at screening: Triglycerides > 500 mg/dl, Low Density Lipoprotein-Cholesterol > 100 mg/dL Any disease or condition or laboratory value that would place the participant at an unacceptable risk.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive subcutaneous (SC) dose of placebo (volume matched to MEDI5884) on Days 1, 31, and 61. | Drug: Placebo<br>* Participants will receive SC dose of placebo (volume matched to MEDI5884) on Days 1, 31, and 61.<br>|
| Experimental: MEDI5884 50 mg<br>Participants will receive SC dose of MEDI5884 50 mg on Days 1, 31, and 61. | Drug: MEDI5884<br>* Participants will receive SC dose of MEDI5884 50 mg or 100 mg or 200 mg or 350 mg or 500 mg on Days 1, 31, and 61.<br>|
| Experimental: MEDI5884 100 mg<br>Participants will receive SC dose of MEDI5884 100 mg on Days 1, 31, and 61. | Drug: MEDI5884<br>* Participants will receive SC dose of MEDI5884 50 mg or 100 mg or 200 mg or 350 mg or 500 mg on Days 1, 31, and 61.<br>|
| Experimental: MEDI5884 200 mg<br>Participants will receive SC dose of MEDI5884 200 mg on Days 1, 31, and 61. | Drug: MEDI5884<br>* Participants will receive SC dose of MEDI5884 50 mg or 100 mg or 200 mg or 350 mg or 500 mg on Days 1, 31, and 61.<br>|
| Experimental: MEDI5884 350 mg<br>Participants will receive SC dose of MEDI5884 350 mg on Days 1, 31, and 61. | Drug: MEDI5884<br>* Participants will receive SC dose of MEDI5884 50 mg or 100 mg or 200 mg or 350 mg or 500 mg on Days 1, 31, and 61.<br>|
| Experimental: MEDI5884 500 mg<br>Participants will receive SC dose of MEDI5884 500 mg on Days 1, 31, and 61. | Drug: MEDI5884<br>* Participants will receive SC dose of MEDI5884 50 mg or 100 mg or 200 mg or 350 mg or 500 mg on Days 1, 31, and 61.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is 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. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | Day 1 (Baseline) through Day 241 | 
| Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | Number of participants with clinically important changes in ECGs from baseline are reported. Clinically important changes in ECGs is defined as any clinical significant difference in heart rate, RR interval, PR interval, QRS, and QT intervals from the primary lead of the digital 12-lead ECG from baseline. | Day 1 (Baseline) through Day 241 | 
| Number of Participants With Clinically Important Changes in Vital Signs From Baseline | Number of participants with clinically important changes in vital signs from baseline are reported. Vital signs measurements were obtained after the participant had rested in the supine position for at least 10 minutes at the recording time. Clinically important changes in vital signs from baseline is defined as any clinical significant difference in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate) from baseline. | Day 1 (Baseline) through Day 241 | 
| Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | Number of participants with clinically important changes in laboratory parameters from baseline are reported. Clinically important changes in laboratory parameters is defined as any clinical significant difference in analysis of serum chemistry, hematology, and urine from baseline. | Day 1 (Baseline) through Day 241 | 
| Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | Number of participants with clinically important changes in physical examinations from baseline are reported. Clinically important changes in physical examinations is defined as any clinical significant difference in general appearance, head, ears, eyes, nose, throat, neck, skin, heart, lung, abdomen, musculoskeletal system, endocrine system, nervous system, height, and weight from baseline. | Day 1 (Baseline) through Day 241 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Apolipoprotein B | Change from baseline in apolipoprotein B is reported. | Day 1 (Baseline), and Days 31, 61, and 91 | 
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Percent change from baseline in HDL-C is reported. | Day 1 (Baseline), and Days 31, 61, and 91 | 
| Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | AUC30d after the last dose of MEDI5884 is reported. | Day 61 (pre-dose), and on Days 64, 68, 71, and 91 | 
| Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | Maximum observed serum concentration (Cmax) of MEDI5884 after the last dose is reported. | Day 61 (pre-dose), and on Days 64, 68, 71, 91, 111, and 151 | 
| Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose | Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of MEDI5884 after the last dose is reported. | Day 61 (pre-dose), and on Days 64, 68, 71, 91, 111, and 151 | 
| Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post baseline-positive only) and treatment-boosted ADA (baseline ADA titer that was boosted to a 4-fold or higher level following drug administration). | Day 1 (pre-dose), on Day 8, Day 31 (pre-dose), Day 61 (pre-dose), on Days 151 and 241 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronary heart disease, Pharmacokinetic, Pharmacodynamics