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

NCT02678923 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MDCO-APO-15-012015-000826-13
• Study Type: interventional
• Target: 126
• Locations: 5 countries
• Sites: 20

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Day 36

Secondary Outcomes (4)

• Change From Baseline In Total Atheroma Volume (TAV) At Day 36

  Baseline, Day 36

• Change From Baseline In TAV For The 10 Millimeters (mm) Subsegment With The Greatest Disease Burden At Day 36

  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

  Baseline through Day 36

• Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change <0

  Baseline through Day 36

Study Arms (2)

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

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

Drug: Placebo

Interventions

MDCO-216 DRUG

Also known as: Recombinant Apo A-I Milano (rApoA-IM)

MDCO-216

Placebo DRUG

Also known as: NaCl Solution

Placebo

Eligibility Criteria

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

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.
• 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.
• Males who are unwilling to use an acceptable method of birth control during the entire study period (such as, condom with spermicide).

Sponsors & Collaborators

• The Medicines Company: lead
• The Cleveland Clinic: collaborator

Study Sites (20)

Unknown Facility

London, Canada

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Québec, Canada

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Winnipeg, Canada

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Brno, Czechia

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Hradec Králové, Czechia

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Prague, Czechia

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Budapest, Hungary

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Szeged, Hungary

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Alkmaar, Netherlands

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Amsterdam, Netherlands

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Nijmegen, Netherlands

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Venlo, Netherlands

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Bielsko-Biala, Poland

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Chrzanów, Poland

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Dąbrowa Górnicza, Poland

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Katowice, Poland

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Kędzierzyn-Koźle, Poland

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Krakow, Poland

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Tychy, Poland

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Warsaw, Poland

Location

Related Publications (1)

• 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.

  PMID: 30046837 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

MDCO-216; Saline Solution

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Global Health Science Center
• Organization: The Medicines Company

medical.information@themedco.com

1-888-977-6326

Study Officials

• Stephen Nicholls, MBSS, PhD

  South Australian Health & Medical Research Institute (SAHMRI) in Adelaide, Australia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: February 10, 2016
• Study Start: December 3, 2015
• Primary Completion: October 26, 2016
• Study Completion: October 26, 2016
• Last Updated: July 13, 2017
• Results First Posted: July 13, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); CA (3); CZ (3); NL (4); PL (8)