Acute Coronary SyndromePhase 1/2PILOTNCT02678923
MDCO-216 Infusions Leading to Changes in Atherosclerosis: A Novel Therapy in Development to Improve Cardiovascular Outcomes - Proof of Concept Intravascular Ultrasound (IVUS), Lipids, and Other Surrogate Biomarkers Trial
A Phase 1/2 study testing MDCO-216 in people with Acute Coronary Syndrome, run by The Medicines Company at 20 sites in 5 countries.
Trial summary
This study will be a proof-of-concept, placebo-controlled, double-blind, randomized trial in participants with a recent acute coronary syndrome (ACS) to evaluate the efficacy, pharmacokinetics, safety, tolerability, disease progression measures by IVUS, and pharmacodynamics of MDCO-216 infusion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Coronary Syndrome
- What is being tested?
- MDCO-216
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 20 sitesin 5 countries
- Study dates
- 3 Dec 2015to 26 Oct 2016
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have experienced a recent ACS event within 14 days of screening that requires a clinically indicated coronary angiogram.
- A qualifying ACS event will be defined as follows: a diagnosis of a qualifying myocardial infarction (MI) event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or creatine kinase myoglobin [CK-MB] mass) with at least one determination greater than the 99th percentile or upper limits of normal (ULN) for the laboratory and at least one of the following: chest discomfort or symptoms of myocardial ischemia (≥10 minutes) at rest within 24 hours prior to hospitalization for MI and/or new electrocardiogram (ECG) findings (or presumed new if no prior ECG available) indicative of acute myocardial ischemia in absence of left ventricular hypertrophy (LVH) and left bundle branch block (LBB).
- Baseline coronary angiogram must meet all of the following criteria for IVUS interrogation of target artery:
- Target artery must be accessible to the IVUS catheter
- Target artery must have a stenotic area of ≥20% and <50% in lumen diameter by angiographic visual estimation within the length of the native coronary artery ("target segment") for imaging by IVUS
- Target artery has not undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
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- Target artery is not currently a candidate for intervention or a likely candidate for intervention over the treatment phase of the study and until the second IVUS interrogation at Day 36; the target artery may not be a bypass graft
- Target artery may not be the culprit vessel for a previous MI.
- The target artery may have the following:
- A lesion of up to 60% stenosis, distal to the target segment, provided that this area is not a target for PCI or CABG
- A single branch of the "target vessel" may have a narrowing ≤70% by visual estimation, provided that the branch in question is not a target for PCI or CABG.
- Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
Who cannot join
- Baseline IVUS not completed due to non-qualifying coronary angiogram as demonstrated by a greater than 50% reduction in lumen of the left main coronary artery by visual estimation, or extensive coronary artery disease (CAD) with no target vessel for IVUS interrogation.
- Baseline IVUS interrogation determined to be unacceptable by the Atherosclerosis Imaging Core Laboratory.
- ST-segment elevation myocardial infarction (STEMI) within the last 90 days
- Clinically significant heart disease which, in the opinion of the Investigator, is likely to require CABG, PCI cardiac transplantation, surgical or percutaneous valve repair, and/or replacement following index IVUS imaging (does not apply to PCI that occurs as a result of initial screening angiogram and completed prior to index IVUS imaging).
- New York Heart Failure Association Class III or IV heart failure or last known left ventricular ejection fraction <30%.
- Coronary artery bypass surgery <6 weeks prior to the qualifying IVUS.
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- Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication.
- Uncontrolled severe hypertension: systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy.
- Poorly controlled diabetes mellitus and a hemoglobin A1c (HbA1c) >10.0% prior to randomization.
- Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or alanine aminotransferase, aspartate aminotransferase elevation >2 x ULN or total bilirubin elevation >1.5 x ULN at screening confirmed by a repeat measurement at least one week apart.
- Fasting triglyceride value >400 milligrams/deciliter (mg/dL).
- Impaired kidney function defined as calculated glomerular filtration rate <60 mL/minute by estimated glomerular filtration rate. In addition, participants with a 0.3 mg/dL or 25% increase in serum creatinine in the initial 3 to 5 days following angiography will be excluded from the study.
- Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (such as, acute systemic infection, cancer, or other serious illnesses). This includes all cancers with the exception of treated basal-cell carcinoma occurring >3 years before screening.
- Body weight >120 kg.
- Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal litigation). Women who are >2 years postmenopausal defined as ≥1 year since last menstrual period and are <55 years old with a negative pregnancy test within 24 hours of randomization or surgically sterile are exempt from this exclusion.
- Males who are unwilling to use an acceptable method of birth control during the entire study period (such as, condom with spermicide).
- Previous participation (enrollment and randomization) in this study or any preceding study with ETC-216 (predecessor compound of MDCO-216), MDCO-216, or similar investigational medicines containing apolipoprotein A-I (ApoA-I) proteins.
- Known allergy to the phospholipid or any other component of the investigational product (dimeric recombinant ApoA-IM, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, or mannitol and sucrose in phosphate buffer).
- Treatment with other investigational medicinal products or devices within 30 days or 5 half˗lives, whichever is longer.
- Known history of alcohol and/or drug abuse.
- Use of other investigational medicinal products or devices during the course of the study, excluding Post-Marketing Registries.
- Any condition that according to the investigator could interfere with the conduct of the study.
Trial locations and contacts
20 sites in 5 countries.
20 sites in 5 countries
Poland8 sites
Study site
Bielsko-Biala
Study site
Chrzanów
Study site
Dąbrowa Górnicza
Study site
Katowice
Study site
Kędzierzyn-Koźle
Study site
Krakow
Study site
Tychy
Study site
Warsaw
Netherlands4 sites
Study site
Alkmaar
Study site
Amsterdam
Study site
Nijmegen
Study site
Venlo
About this study
Official title: A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Treatment on Plaque Burden as Determined by Intravascular Ultrasound and to Evaluate the Efficacy, Pharmacokinetics, Safety, and Tolerability of MDCO-216 Given as Multiple Weekly Infusions in Subjects With a Recent Acute Coronary Syndrome
This study will be a proof-of-concept, placebo-controlled, double-blind, randomized trial in participants with a recent acute coronary syndrome (ACS) to evaluate the efficacy, pharmacokinetics, safety, tolerability, disease progression measures by IVUS, and pharmacodynamics of MDCO-216 infusion. Eligible participants will be randomized to receive 5 infusions of MDCO-216 20 milligrams/kilogram (mg/kg) or placebo in a 1:1 ratio.
- Conditions
- Acute Coronary Syndrome
- Being tested
- MDCO-216, Placebo
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MDCO-216Drug
Also called Recombinant Apo A-I Milano (rApoA-IM)
PlaceboDrug
Also called NaCl Solution
| Study group | Role | What they receive |
|---|---|---|
| MDCO-216 | Experimental | 20 mg/kg of MDCO-216 administered intravenously (IV) as a 360 milliliter (mL) infusion over 2 hours on Days 1, 8, 15, 22, and 29 Receives: Drug: MDCO-216 |
| Placebo | Placebo comparator | 360 mL of placebo (0.9% sodium chloride [NaCl] solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline In Percent Atheroma Volume (PAV) At Day 36
Change from Baseline to Day 36 post-randomization in PAV in a targeted (imaged) coronary artery for all anatomically comparable slices, as determined by IVUS. The change is calculated by subtracting the value at Baseline from the value at Day 36, with positive numbers to represent increases and negative numbers to represent decreases. Change in PAV was analyzed using an analysis of covariance (ANCOVA) model that included Baseline PAV as a covariate and treatment group as factor. Least Squares (LS) mean was adjusted for stratification factors of country and prior statin use.
Measured: Baseline, Day 36
Secondary outcomes (4)
Change From Baseline In Total Atheroma Volume (TAV) At Day 36
Change from Baseline to Day 36 post-randomization in normalized TAV in a targeted (imaged) coronary artery for all anatomically comparable slices, as determined by IVUS. The change is calculated by subtracting the value at Baseline from the value at Day 36, with positive numbers to represent increases and negative numbers to represent decreases. Change in TAV was analyzed using an analysis of covariance (ANCOVA) model that included Baseline TAV as a covariate and treatment group as factor. LS mean was adjusted for stratification factors of country and prior statin use.
Measured: Baseline, Day 36
Change From Baseline In TAV For The 10 Millimeters (mm) Subsegment With The Greatest Disease Burden At Day 36
Change in TAV from Baseline to Day 36 post-randomization of the most diseased 10-mm subsegment, as determined by IVUS. The change is calculated by subtracting the value at Baseline from the value at Day 36, with positive numbers to represent increases and negative numbers to represent decreases. Change in TAV was analyzed using an analysis of covariance (ANCOVA) model that included Baseline TAV for the most diseased 10-mm subsegment as a covariate and treatment group as factor. LS mean was adjusted for stratification factors of country and prior statin use.
Measured: Baseline, Day 36
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change Greater Than 2 Standard Deviations Of Test-Retest Measurement Variability
The number of participants with regression of coronary atherosclerosis is presented. For this Outcome Measure, the regression of coronary atherosclerosis is defined as a reduction in PAV from Baseline to Day 36 of greater than 2 standard deviations of the test-retest variability.
Measured: Baseline through Day 36
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change <0
The number of participants with regression of coronary atherosclerosis is presented. For this Outcome Measure, the regression of coronary atherosclerosis is defined as a change in PAV from Baseline to Day 36 of less than zero.
Measured: Baseline through Day 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study start3 Dec 2015
- Primary completion26 Oct 2016
- Study completion26 Oct 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Medicines Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic
- Responsible party
- Sponsor
- Investigators
- Stephen Nicholls, MBSS, PhD, Principal investigator, South Australian Health & Medical Research Institute (SAHMRI) in Adelaide, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02678923
- Sponsor's protocol ID
- MDCO-APO-15-01
- Other IDs
- 2015-000826-13, 2015
- Acronym
- PILOT
- Status last verified
- Jun 2017
- First submitted
- 5 Feb 2016
- Last updated
- 13 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nicholls SJ, Puri R, Ballantyne CM, Jukema JW, Kastelein JJP, Koenig W, Wright RS, Kallend D, Wijngaard P, Borgman M, Wolski K, Nissen SE. Effect of Infusion of High-Density Lipoprotein Mimetic Containing Recombinant Apolipoprotein A-I Milano on Coronary Disease in Patients With an Acute Coronary Syndrome in the MILANO-PILOT Trial: A Randomized Clinical Trial. JAMA Cardiol. 2018 Sep 1;3(9):806-814. doi: 10.1001/jamacardio.2018.2112.
PubMed 30046837
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Treatment on Plaque Burden as Determined by Intravascular Ultrasound and to Evaluate the Efficacy, Pharmacokinetics, Safety, and Tolerability of MDCO-216 Given as Multiple Weekly Infusions in Subjects With a Recent Acute Coronary Syndrome
- ClinicalTrials.gov ID
- NCT02678923
- Acronym / sponsor ID
- PILOT / MDCO-APO-15-01
- Conditions
- Acute Coronary Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- The Medicines CompanyIndustry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic
- Study start
- 3 Dec 2015 (actual)
- Primary completion
- 26 Oct 2016 (actual)
- Study completion
- 26 Oct 2016 (actual)
- First posted
- 10 Feb 2016 (estimated)
- Results
- Posted 13 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be a proof-of-concept, placebo-controlled, double-blind, randomized trial in participants with a recent acute coronary syndrome (ACS) to evaluate the efficacy, pharmacokinetics, safety, tolerability, disease progression measures by IVUS, and pharmacodynamics of MDCO-216 infusion. Eligible participants will be randomized to receive 5 infusions of MDCO-216 20 milligrams/kilogram (mg/kg) or placebo in a 1:1 ratio.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MDCO-216 | Experimental | Drug: MDCO-21620 mg/kg of MDCO-216 administered intravenously (IV) as a 360 milliliter (mL) infusion over 2 hours on Days 1, 8, 15, 22, and 29 |
| Placebo | Placebo comparator | Drug: Placebo360 mL of placebo (0.9% sodium chloride [NaCl] solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Have experienced a recent ACS event within 14 days of screening that requires a clinically indicated coronary angiogram.
- A qualifying ACS event will be defined as follows: a diagnosis of a qualifying myocardial infarction (MI) event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or creatine kinase myoglobin [CK-MB] mass) with at least one determination greater than the 99th percentile or upper limits of normal (ULN) for the laboratory and at least one of the following: chest discomfort or symptoms of myocardial ischemia (≥10 minutes) at rest within 24 hours prior to hospitalization for MI and/or new electrocardiogram (ECG) findings (or presumed new if no prior ECG available) indicative of acute myocardial ischemia in absence of left ventricular hypertrophy (LVH) and left bundle branch block (LBB).
- Baseline coronary angiogram must meet all of the following criteria for IVUS interrogation of target artery:
- A lesion of up to 60% stenosis, distal to the target segment, provided that this area is not a target for PCI or CABG
- A single branch of the "target vessel" may have a narrowing ≤70% by visual estimation, provided that the branch in question is not a target for PCI or CABG.
Key exclusion criteria (22 listed)
- Baseline IVUS not completed due to non-qualifying coronary angiogram as demonstrated by a greater than 50% reduction in lumen of the left main coronary artery by visual estimation, or extensive coronary artery disease (CAD) with no target vessel for IVUS interrogation.
- Baseline IVUS interrogation determined to be unacceptable by the Atherosclerosis Imaging Core Laboratory.
- ST-segment elevation myocardial infarction (STEMI) within the last 90 days
- Clinically significant heart disease which, in the opinion of the Investigator, is likely to require CABG, PCI cardiac transplantation, surgical or percutaneous valve repair, and/or replacement following index IVUS imaging (does not apply to PCI that occurs as a result of initial screening angiogram and completed prior to index IVUS imaging).
- New York Heart Failure Association Class III or IV heart failure or last known left ventricular ejection fraction <30%.
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 |
|---|---|---|
| MDCO-216Also: Recombinant Apo A-I Milano (rApoA-IM) | Drug | MDCO-216 |
| PlaceboAlso: NaCl Solution | Drug | Placebo |
Primary outcome
Change From Baseline In Percent Atheroma Volume (PAV) At Day 36
Time frame: Baseline, Day 36
Change from Baseline to Day 36 post-randomization in PAV in a targeted (imaged) coronary artery for all anatomically comparable slices, as determined by IVUS. The change is calculated by subtracting the value at Baseline from the value at Day 36, with positive numbers to represent increases and negative numbers to represent decreases. Change in PAV was analyzed using an analysis of covariance (ANCOVA) model that included Baseline PAV as a covariate and treatment group as factor. Least Squares (LS) mean was adjusted for stratification factors of country and prior statin use.
4 secondary outcomes
Change From Baseline In Total Atheroma Volume (TAV) At Day 36
Time frame: Baseline, Day 36
Change From Baseline In TAV For The 10 Millimeters (mm) Subsegment With The Greatest Disease Burden At Day 36
Time frame: Baseline, Day 36
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change Greater Than 2 Standard Deviations Of Test-Retest Measurement Variability
Time frame: Baseline through Day 36
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change <0
Time frame: Baseline through Day 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30046837Nicholls SJ, Puri R, Ballantyne CM, Jukema JW, Kastelein JJP, Koenig W, Wright RS, Kallend D, Wijngaard P, Borgman M, Wolski K, Nissen SE. Effect of Infusion of High-Density Lipoprotein Mimetic Containing Recombinant Apolipoprotein A-I Milano on Coronary Disease in Patients With an Acute Coronary Syndrome in the MILANO-PILOT Trial: A Randomized Clinical Trial. JAMA Cardiol. 2018 Sep 1;3(9):806-814. doi: 10.1001/jamacardio.2018.2112.
- 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.
Stephen Nicholls, MBSS, PhD principal investigator
South Australian Health & Medical Research Institute (SAHMRI) in Adelaide, Australia
20 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MDCO-216 in people with Acute Coronary Syndrome, run by The Medicines Company at 20 sites in 5 countries.
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 12 inclusion and 22 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: finished, as of the sponsor's last update on 13 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Poland, Netherlands, Canada, Czechia, Hungary. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 13 Jul 2017). 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?
Change From Baseline In Percent Atheroma Volume (PAV) At Day 36 (time frame: Baseline, Day 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02678923, which also lists 1 linked publication.
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 13 Jul 2017.