Cardiovascular DiseasesPhase 2NCT03773172
Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism
A Phase 2 study testing MEDI6012 in people with Cardiovascular Diseases, run by Columbia University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Cardiovascular Diseases
- What is being tested?
- MEDI6012
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2019to 31 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
- Use of lipid-lowering medications, with the exception of statins and ezetimibe, and the following dietary supplements: ≥ 2 grams/day of fish oil (≥ 2 grams/day docosahexaenoic acid (DHA) and EPA combined), ≥ 30 grams/day of flaxseed oil or ground flaxseed, red yeast extract, > 100 mg/day of niacin. At the investigator's discretion, subjects may undergo a 6-week washout period of any exclusionary lipid-lowering agents with the expectation that post-washout lipid levels will be rechecked and acceptable per above criteria.
- 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
- History of clinically overt chronic liver disease or biochemical evidence of liver disease
- Poorly controlled endocrine disorder including:
- Type 1 Diabetes excluded
- Type 2 Diabetes Mellitus with glycated hemoglobin (HbA1c) > 8.0% as assessed at screening or
- Uncontrolled thyroid disorder defined as thyroid stimulating hormone (TSH)> upper limit of normal (ULN) and abnormal free T4; subjects with thyroid deficiency should have received a stable dose of thyroid hormone for > 6 weeks prior to screening and have a normal TSH.
- Current or previous use of systemic corticosteroids within 28 days prior to screening. Topical, intra-articular, intranasal, inhaled, and ophthalmic steroid therapies are allowed
- History of severe infection or ongoing febrile illness within 30 days of screening, or a medical history of a chronic viral illness including hepatitis B or C virus, or human immunodeficiency virus (HIV).
- History of active malignancy within 5 years (subjects with non-melanotic skin cancer may be included)
- Any other disease or condition or laboratory value that, in the opinion of the investigator or medical monitor, would place the subject at an unacceptable risk or interfere with the evaluation of the investigative product.
- Known allergy/hypersensitivity to any component of the investigational product formulation, other biologics, IV infusion equipment, plastics, adhesive or silicone, history of infusion site reactions with IV administration of other medicines, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
- Subjects who are legally institutionalized
- Previous Exposure to rhLCAT
- Concurrent enrollment in another clinical study of any investigational drug therapy or use of any biologicals within 6 months prior to screening or within 5 half-lives of an investigational agent or biologic, whichever is longer.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Study to Evaluate the Effects of Two Doses Over 48 Hours of MEDI6012 on Apolipoprotein B100 Metabolism in Subjects With Stable Atherosclerotic Cardiovascular Disease
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).
Read the detailed description
Atherosclerosis, characterized by excess fat deposit in arteries, is a progressive and life-threatening condition. Therefore, treatments that can remove fat deposits from the arteries are being developed. These treatments may prevent subsequent heart attacks or other cardiovascular events, addressing an unmet medical need. MEDI16012 is a new drug that targets a substance produced by the body to assist participants in breaking down the bodies "good" fat. The investigators are interested in understanding why MEDI6012 increases the good fat, but also why it increases other types of "bad" fat such as low-density lipoprotein-C (LDL-C).
- Conditions
- Cardiovascular Diseases
- Being tested
- MEDI6012, Placebo
- Keywords
- Lipid and Lipoprotein Metabolism
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI6012Drug
Also called Stable Isotopes
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.
PlaceboDrug
Also called Placebo compound provided by funding agency
The placebo will mimic the active treatment.
| Study group | Role | What they receive |
|---|---|---|
| Placebo Control Group | Placebo comparator | Subjects will receive placebo treatment to mimic active treatment. Receives: 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. Receives: Drug: MEDI6012 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 48 hours from first dose
Secondary outcomes (1)
Production Rate (PR) of Apolipoprotein B100 (mg/kg/Day)
Amount of Apolipoprotein B100 (measured as mg/kg) produced in participants per day.
Measured: Up to 48 hours from first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2018
- Study start31 Jan 2019
- Primary completion31 Aug 2020
- Study completion31 Aug 2020
Why it stopped: Early termination due to COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- MedImmune LLC, AstraZeneca
- Responsible party
- Principal investigator, Henry N. Ginsberg, Columbia University
- Investigators
- Henry Ginsberg, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03773172
- Sponsor's protocol ID
- AAAS0459
- Status last verified
- Oct 2024
- First submitted
- 10 Dec 2018
- Last updated
- 12 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Effects of Two Doses Over 48 Hours of MEDI6012 on Apolipoprotein B100 Metabolism in Subjects With Stable Atherosclerotic Cardiovascular Disease
- ClinicalTrials.gov ID
- NCT03773172
- Acronym / sponsor ID
- AAAS0459
- Conditions
- Cardiovascular Diseases
- Keywords
- Lipid and Lipoprotein Metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination due to COVID-19
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- MedImmune LLC, AstraZeneca
- Study start
- 31 Jan 2019 (actual)
- Primary completion
- 31 Aug 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 12 Dec 2018 (actual)
- Results
- Posted 12 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Atherosclerosis, characterized by excess fat deposit in arteries, is a progressive and life-threatening condition. Therefore, treatments that can remove fat deposits from the arteries are being developed. These treatments may prevent subsequent heart attacks or other cardiovascular events, addressing an unmet medical need. MEDI16012 is a new drug that targets a substance produced by the body to assist participants in breaking down the bodies "good" fat. The investigators are interested in understanding why MEDI6012 increases the good fat, but also why it increases other types of "bad" fat such as low-density lipoprotein-C (LDL-C).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo Control Group | Placebo comparator | Drug: PlaceboSubjects will receive placebo treatment to mimic active treatment. |
| Active treatment | Active comparator | Drug: MEDI6012IV push loading dose of 300 mg MEDI6012 followed by a 150 mg maintenance dose of MEDI6012 at 48 hours. |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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.
Key exclusion criteria (29 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI6012Also: Stable IsotopesMEDI6012 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. | Drug | Active treatment |
| PlaceboAlso: Placebo compound provided by funding agencyThe placebo will mimic the active treatment. | Drug | Placebo Control Group |
Primary outcome
Fractional Clearance Rate (FCR) of Lipoprotein B (Pools/Day)
Time frame: Up to 48 hours from first dose
FCR is the rate of synthesis and clearance of soluble lipoprotein B in participants per day.
1 secondary outcome
Production Rate (PR) of Apolipoprotein B100 (mg/kg/Day)
Time frame: Up to 48 hours from first dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henry Ginsberg, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MEDI6012 in people with Cardiovascular Diseases, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fractional Clearance Rate (FCR) of Lipoprotein B (Pools/Day) (time frame: Up to 48 hours from first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.