Multiple Ascending Doses of MEDI6012 in Subjects With Stable Atherosclerotic Cardiovascular Disease

NCT03004638 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D5780C00005
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

To evaluate the safety pharmacokinetics, and pharmacodynamics of repeat weekly dosing of MEDI6012 in subjects with stable atherosclerosis.

Conditions

Atherosclerosis; Cardiovascular Disease

Keywords

Atherosclerosis; Cardiovascular Disease; CAD; Atherosclerotic Cardiovascular Disease

Outcome Measures

Primary Outcomes (7)

• 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. An 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. Treatment-emergent are the events between first dose of study drug and up to 56 days after last dose of study drug (Day 66 for Cohort 4 and placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm) that were absent before treatment or that worsened relative to pre-treatment state.

  From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)

• Number of Participants With Abnormal Clinical Laboratory Evaluations Reported as TEAEs

  An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis.

  From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)

• Number of Participants With Abnormal Vital Signs Reported as TEAEs

  Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported. Vital sign parameters included blood pressure, respiration rate, heart rate, pulse oximetry, and body temperature.

  From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)

• Number of Participants With Abnormal Electrocardiogram Reported as TEAEs

  Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported.

  From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)

• Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for High-density Lipoprotein-cholesterol (HDL-C)

  The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of high-density lipoprotein-cholesterol.

  Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.

• Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for High-density Lipoprotein-cholesterol Ester (HDL-CE)

  The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of high-density lipoprotein-cholesterol ester.

  Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.

• Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Cholesterol Ester

  The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of cholesterol ester.

  Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.

Secondary Outcomes (11)

• Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein A1

  Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.

• Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Low-density Lipoprotein Cholesterol (LDL-C).

  Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.

• Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein B

  Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.

• Change From Baseline in Serum Concentration for MEDI6012 Mass

  Seven days post-dose following Doses 1 to 3 in Cohorts 1 to 3 and placebo arm (Days 8, 15, 22); 2 days post-dose following Dose 1 (Day 3) and 7 days post-dose following Doses 2 and 3 (Days 10, 17) in Cohort 4 and placbo IV push.

• Change From Baseline in Serum Concentration for Total LCAT Activity

  Seven days post-dose following Doses 1 to 3 in Cohorts 1 to 3 and placebo arm (Days 8, 15, 22); 2 days post-dose following Dose 1 (Day 3) and 7 days post-dose following Doses 2 and 3 (Days 10, 17) in Cohort 4 and placbo IV push.

Study Arms (6)

MEDI6012 40 mg

EXPERIMENTAL

Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.

Drug: MEDI6012 40 mg

Placebo

PLACEBO COMPARATOR

Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.

Drug: Placebo

MEDI6012 120 mg

EXPERIMENTAL

Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.

Drug: MEDI6012 120 mg

MEDI6012 300 mg

EXPERIMENTAL

Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.

Drug: MEDI6012 300 mg

MEDI6012 IV Push

EXPERIMENTAL

Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.

Drug: MEDI6012 IV Push

Placebo IV Push

PLACEBO COMPARATOR

Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.

Drug: Placebo IV Push

Interventions

MEDI6012 40 mg DRUG

Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.

MEDI6012 40 mg

Placebo DRUG

Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.

Placebo

MEDI6012 120 mg DRUG

Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.

MEDI6012 120 mg

MEDI6012 300 mg DRUG

Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.

MEDI6012 300 mg

Placebo IV Push DRUG

Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.

Placebo IV Push

MEDI6012 IV Push DRUG

Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.

MEDI6012 IV Push

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-childbearing potential
• Diagnosis of stable atherosclerotic CVD
• Currently receiving a stable dose of Statin

You may not qualify if:

• Unstable cardiovascular condition within 3 months of screening
• Elective arterial revascularization with in the past month
• Any planned arterial revascularization
• Body mass index \<18 or \>45
• Clinically significant ECG that may interfere with the interpretation of serial ECG and QT interval changes at screening
• Chronic kidney disease defined by estimated glomerular filtration rate of less than 30 mL/mim/1.73m2
• Triglycerides greater than 500 mg/dL, LDL-C greater than 160 mg/dL, or HDL-C greater than 60 for males, or 65 for females
• Clinically significant vital sign abnormalities
• Genetic disorder of cholesterol metabolism
• History of overt liver disease
• Poorly controlled endocrine disorder (Diabetes or Thyroid disorder)
• Current or recent use of systemic corticosteroids
• Recent or ongoing infection or febrile illness
• History of active malignancy within 5 years
• History of alcohol or recreational substance abuse in the past 6 months

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (4)

Research Site

Anniston, Alabama, 36207, United States

Location

Research Site

Jacksonville, Florida, 32216, United States

Location

Research Site

Port Orange, Florida, 32127, United States

Location

Research Site

Cincinnati, Ohio, 45246, United States

Location

Related Links

• D5780C00005-CSP-amendment-1\_REDACTED\_16Jul2017\_PDF-A
• 5780C00005 MEDI6012 Statistical Analysis Plan\_21Jul2017\_Version2\_Redacted\_PDF-A.pdf

MeSH Terms

Conditions

Atherosclerosis; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Richard George
• Organization: MedImmune LLC

information.center@astrazenea.com

+1-301-398-5681

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 29, 2016
• Study Start: January 23, 2017
• Primary Completion: November 2, 2017
• Study Completion: November 2, 2017
• Last Updated: December 19, 2018
• Results First Posted: November 30, 2018

Record last verified: 2018-11

Locations

US (4)