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

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

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

Study Overview

• Status: Completed
• Conditions: Stable Coronary Heart Disease
• Intervention / Treatment: Drug: Placebo; Drug: MEDI5884

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.

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
    • Huntsville, Alabama, United States, 35801
      • Research Site
  • California
    • El Cajon, California, United States, 92020
      • Research Site
    • Lincoln, California, United States, 95648
      • Research Site
    • Northridge, California, United States, 91325
      • Research Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Pembroke Pines, Florida, United States, 33024
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Research Site
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Marion, Ohio, United States, 43302
      • Research Site
    • Stow, Ohio, United States, 44224
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73134
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Research Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Research Site
  • Texas
    • McAllen, Texas, United States, 78503
      • Research Site
    • San Antonio, Texas, United States, 78228
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants will receive subcutaneous (SC) dose of placebo (volume matched to MEDI5884) on Days 1, 31, and 61.	Drug: Placebo; Participants will receive SC dose of placebo (volume matched to MEDI5884) on Days 1, 31, and 61.
EXPERIMENTAL: MEDI5884 50 mg; Participants will receive SC dose of MEDI5884 50 mg on Days 1, 31, and 61.	Drug: MEDI5884; 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.
EXPERIMENTAL: MEDI5884 100 mg; Participants will receive SC dose of MEDI5884 100 mg on Days 1, 31, and 61.	Drug: MEDI5884; 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.
EXPERIMENTAL: MEDI5884 200 mg; Participants will receive SC dose of MEDI5884 200 mg on Days 1, 31, and 61.	Drug: MEDI5884; 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.
EXPERIMENTAL: MEDI5884 350 mg; Participants will receive SC dose of MEDI5884 350 mg on Days 1, 31, and 61.	Drug: MEDI5884; 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.
EXPERIMENTAL: MEDI5884 500 mg; Participants will receive SC dose of MEDI5884 500 mg on Days 1, 31, and 61.	Drug: MEDI5884; 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.

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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Principal Investigator: Michael J Koren, MD, FACC, Jacksonville Center for Clinical Research

Publications and helpful links

General Publications

• Ruff CT, Koren MJ, Grimsby J, Rosenbaum AI, Tu X, Karathanasis SK, Falloon J, Hsia J, Guan Y, Conway J, Tsai LF, Hummer BT, Hirshberg B, Kuder JF, Murphy SA, George RT, Sabatine MS. LEGACY: Phase 2a Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of the Anti-EL (Endothelial Lipase) Antibody MEDI5884 in Patients With Stable Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2021 Dec;41(12):3005-3014. doi: 10.1161/ATVBAHA.120.315757. Epub 2021 Oct 28.

Helpful Links

• D7870C00002 Clinical Protocol Redacted
• D7870C00002 Statistical Analysis Plan Redacted

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 13, 2017
• Primary Completion (ACTUAL): November 9, 2018
• Study Completion (ACTUAL): November 9, 2018

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (ACTUAL): November 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Coronary heart disease; Pharmacokinetic; Pharmacodynamics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: D7870C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No