Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism

NCT03773172 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: AAAS0459
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, single-center, placebo controlled, double-blind, randomized crossover study to determine the effects of MEDI6012 on the metabolism of apolipoprotein B100 (apoB100) lipoproteins in individuals with stable atherosclerotic cardiovascular disease (ASCVD).

Conditions

Cardiovascular Diseases

Keywords

Lipid and Lipoprotein Metabolism

Outcome Measures

Primary Outcomes (1)

• Fractional Clearance Rate (FCR) of Lipoprotein B (Pools/Day)

  FCR is the rate of synthesis and clearance of soluble lipoprotein B in participants per day.

  Up to 48 hours from first dose

Secondary Outcomes (1)

• Production Rate (PR) of Apolipoprotein B100 (mg/kg/Day)

  Up to 48 hours from first dose

Other Outcomes (1)

• ADA Measurement

  Up to 60 days post administration of first dose

Study Arms (2)

Placebo Control Group

PLACEBO COMPARATOR

Subjects will receive placebo treatment to mimic active treatment.

Drug: Placebo

Active treatment

ACTIVE COMPARATOR

IV push loading dose of 300 mg MEDI6012 followed by a 150 mg maintenance dose of MEDI6012 at 48 hours.

Drug: MEDI6012

Interventions

MEDI6012 DRUG

MEDI6012 is recombinant human lecithin-cholesterol acyltransferase (rhLCAT), an approximately 60 kilodalton, glycosylated, single-chain protein consisting of 416 amino acids produced via Chinese hamster ovary cell culture. It is being explored as an acute treatment to reduce the risk of recurrent cardiovascular events as an adjunct to the standard of care in patients with acute myocardial infarction (MI). MEDI6012 and ACP501 have the identical amino acid sequence and are therefore considered the same molecular entity.

Also known as: Stable Isotopes

Active treatment

Placebo DRUG

The placebo will mimic the active treatment.

Also known as: Placebo compound provided by funding agency

Placebo Control Group

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male and female subjects (non-childbearing potential for females) ages 35 through 80 years at the time of screening who are capable of providing informed consent prior to screening and any protocol-related procedures.
• Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act (HIPAA) in the USA) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Ability to complete and meet all eligibility requirements for randomization within 28 days of informed consent (56 days if washing out from lipid altering agent other than statins or ezetimibe).
• A diagnosis of stable atherosclerotic cardiovascular disease (CVD) documented prior to screening:
• Coronary artery disease defined as a history of prior myocardial infarction, coronary revascularization, history of coronary atherosclerosis based on invasive or non-invasive imaging, and/or abnormal stress testing diagnostic of coronary artery disease.
• Carotid artery disease (extracranial internal carotid artery (ICA) stenosis) defined as evidence of carotid atherosclerosis by carotid imaging, or history of percutaneous or surgical carotid revascularization
• Peripheral artery disease defined as ankle-brachial index \< 0.90 and claudication, or prior peripheral revascularization for ischemia, or evidence of lower extremity (below the inguinal ligament) atherosclerosis on invasive or noninvasive imaging
• Currently receiving statin as standard of care, at a stable dose for ≥ 8 weeks prior to screening and intended to remain at a stable dose throughout the study duration. Subjects may also be receiving ezetimibe, 10 mg/day for ≥ 8 weeks prior to screening.
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use condom and spermicide from Day 1 through the end of their participation in the study. Because male condom and spermicide is not a highly effective contraception method it is strongly recommended that female partners of a male study subjects also use a highly effective method of contraception throughout this period.

You may not qualify if:

• Unstable cardiovascular conditions within 3 months prior to screening, including acute coronary syndrome (ACS), stroke or transient ischemia attack, critical limb ischemia, non-elective arterial revascularization, life-threatening arrhythmias, or heart failure hospitalization.
• Elective arterial revascularization (in any vascular territory) in the past 1 month. Any planned arterial revascularization (coronary, peripheral or carotid).
• New York Heart Association (NYHA) Class III or IV congestive heart failure or treatment with advanced therapies (cardiac transplant, ventricular assist device, cardiac resynchronization therapy,and/or chronic IV inotropic support), or severe valvular heart disease.
• Body mass index \< 18 or \> 45.
• Lipid measurements with any of the following:
• Triglycerides (TG) \> 400 mg/dL
• LDL-C \> 120 mg/dL
• High-density lipoprotein C (HDL-C) \> 70 mg/dL for males or \> 80 mg/dL for females.
• Clinically significant vital sign abnormalities at screening or on Day -1:
• Systolic blood pressure (BP) \< 90 or \>160 mm Hg
• Diastolic BP \> 100 mm Hg
• Females currently breastfeeding or of childbearing potential. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal; defined as 12 months with no menses without an alternative medical cause and a follicle-stimulating hormone level in the central laboratory's normal range for post-menopausal phase is required at screening.
• History of any of the following:
• Documented familial hypercholesterolemia
• Chronic kidney disease defined by estimated glomerular filtration rate \< 30 mL/min/1.73 m2 by the modification of diet in renal disease equation, or end stage renal disease treated with kidney transplant or renal replacement therapy

Sponsors & Collaborators

• Columbia University: lead
• MedImmune LLC: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Limitations and Caveats

Double-blind study was terminated early due to COVID-19.

Results Point of Contact

• Title: Henry Ginsberg, MD
• Organization: Columbia University Irving Medical Center

hng1@cumc.columbia.edu

212-305-9562

Study Officials

• Henry Ginsberg, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: 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: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 12, 2018
• Study Start: January 31, 2019
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: November 12, 2024
• Results First Posted: November 12, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)