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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 (PILOT)

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ClinicalTrials.gov Identifier: NCT02678923
Recruitment Status : Completed
First Posted : February 10, 2016
Results First Posted : July 13, 2017
Last Update Posted : July 13, 2017
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: MDCO-216
Drug: Placebo
Enrollment 126
Recruitment Details  
Pre-assignment Details Participants who were screened, enrolled, randomized, received at least one infusion of study drug, and who had an evaluable Baseline and Follow-up intravascular ultrasound (IVUS) assessment were included in the modified intent-to-treat (mITT) population (primary/secondary analyses).
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description 20 milligrams/kilogram (mg/kg) of MDCO-216 administered intravenously (IV) as a 360 milliliter (mL) infusion over 2 hours on Days 1, 8, 15, 22, and 29 360 mL of placebo (0.9% sodium chloride [NaCl] solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
Period Title: Overall Study
Started 59 67
Received at Least 1 Dose of Study Drug [1] 58 64
mITT Population 52 61
Completed 53 62
Not Completed 6 5
Reason Not Completed
Protocol Deviation (Not Dosed)             1             3
Withdrawal by Subject             3             2
Lost to Follow-up             1             0
Did Not Return for Study Visits             1             0
[1]
Randomized participants included in the Safety population.
Arm/Group Title MDCO-216 Placebo Total
Hide Arm/Group Description 20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29 360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29 Total of all reporting groups
Overall Number of Baseline Participants 58 64 122
Hide Baseline Analysis Population Description
Safety population included all participants who received at least one infusion of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 64 participants 122 participants
62.2  (10.6) 61.4  (10.3) 61.8  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 64 participants 122 participants
Female
13
  22.4%
16
  25.0%
29
  23.8%
Male
45
  77.6%
48
  75.0%
93
  76.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 64 participants 122 participants
American Indian or Alaska Native
1
   1.7%
0
   0.0%
1
   0.8%
Asian
0
   0.0%
1
   1.6%
1
   0.8%
Native Hawaiian or Other Pacific Islander
1
   1.7%
0
   0.0%
1
   0.8%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
56
  96.6%
63
  98.4%
119
  97.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 64 participants 122 participants
Canada
3
   5.2%
3
   4.7%
6
   4.9%
Czech Republic
3
   5.2%
2
   3.1%
5
   4.1%
Hungary
6
  10.3%
8
  12.5%
14
  11.5%
Netherlands
8
  13.8%
8
  12.5%
16
  13.1%
Poland
38
  65.5%
43
  67.2%
81
  66.4%
1.Primary Outcome
Title Change From Baseline In Percent Atheroma Volume (PAV) At Day 36
Hide Description 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.
Time Frame Baseline, Day 36
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who were screened, enrolled, randomized, received at least one infusion of study drug, and who had an evaluable Baseline and Follow-up IVUS assessment.
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description:
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
Overall Number of Participants Analyzed 52 61
Least Squares Mean (Standard Error)
Unit of Measure: change in percent
-0.21  (0.386) -0.94  (0.382)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MDCO-216, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0738
Comments Baseline parameter value as a covariate and treatment group as factor, adjusting for country and prior statin use.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
-0.07 to 1.52
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline In Total Atheroma Volume (TAV) At Day 36
Hide Description 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.
Time Frame Baseline, Day 36
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who were screened, enrolled, randomized, received at least one infusion of study drug, and who had an evaluable Baseline and Follow-up IVUS assessment.
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description:
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
Overall Number of Participants Analyzed 52 61
Least Squares Mean (Standard Error)
Unit of Measure: cubic millimeter (mm^3)
-6.33  (3.425) -7.89  (3.354)
3.Secondary Outcome
Title Change From Baseline In TAV For The 10 Millimeters (mm) Subsegment With The Greatest Disease Burden At Day 36
Hide Description 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.
Time Frame Baseline, Day 36
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who were screened, enrolled, randomized, received at least one infusion of study drug, and who had an evaluable Baseline and Follow-up IVUS assessment.
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description:
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
Overall Number of Participants Analyzed 52 61
Least Squares Mean (Standard Error)
Unit of Measure: mm^3
-2.16  (1.809) -1.74  (1.908)
4.Secondary Outcome
Title Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change Greater Than 2 Standard Deviations Of Test-Retest Measurement Variability
Hide Description 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.
Time Frame Baseline through Day 36
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who were screened, enrolled, randomized, received at least one infusion of study drug, and who had an evaluable Baseline and Follow-up IVUS assessment.
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description:
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
Overall Number of Participants Analyzed 52 61
Measure Type: Number
Unit of Measure: participants
NA [1]  NA [1] 
[1]
Test-retest requires IVUS to be done twice at the same time point and retest IVUS was not done.
5.Secondary Outcome
Title Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change <0
Hide Description 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.
Time Frame Baseline through Day 36
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who were screened, enrolled, randomized, received at least one infusion of study drug, and who had an evaluable Baseline and Follow-up IVUS assessment.
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description:
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
Overall Number of Participants Analyzed 52 61
Measure Type: Count of Participants
Unit of Measure: Participants
29
  55.8%
41
  67.2%
Time Frame Up to 59 days (±2 days) post randomization
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MDCO-216 Placebo
Hide Arm/Group Description 20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29 360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
All-Cause Mortality
MDCO-216 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/58 (0.00%)   0/64 (0.00%) 
Hide Serious Adverse Events
MDCO-216 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   10/58 (17.24%)   7/64 (10.94%) 
Cardiac disorders     
Angina unstable  1  1/58 (1.72%)  0/64 (0.00%) 
Atrial flutter  1  1/58 (1.72%)  0/64 (0.00%) 
Coronary artery disease  1  3/58 (5.17%)  2/64 (3.13%) 
Ventricular extrasystoles  1  1/58 (1.72%)  0/64 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  0/58 (0.00%)  1/64 (1.56%) 
General disorders     
Non-cardiac chest pain  1  0/58 (0.00%)  1/64 (1.56%) 
Vessel puncture site haemorrhage  1  0/58 (0.00%)  1/64 (1.56%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/58 (1.72%)  0/64 (0.00%) 
Hepatitis acute  1  1/58 (1.72%)  0/64 (0.00%) 
Infections and infestations     
Urinary tract infection  1  1/58 (1.72%)  0/64 (0.00%) 
Injury, poisoning and procedural complications     
Coronary artery restenosis  1  0/58 (0.00%)  1/64 (1.56%) 
Investigations     
Echocardiogram abnormal  1  1/58 (1.72%)  0/64 (0.00%) 
Nervous system disorders     
Syncope  1  1/58 (1.72%)  0/64 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary oedema  1  0/58 (0.00%)  1/64 (1.56%) 
Vascular disorders     
Deep vein thrombosis  1  1/58 (1.72%)  1/64 (1.56%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
MDCO-216 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   24/58 (41.38%)   12/64 (18.75%) 
Blood and lymphatic system disorders     
Anaemia  1  3/58 (5.17%)  4/64 (6.25%) 
Cardiac disorders     
Bradycardia  1  3/58 (5.17%)  1/64 (1.56%) 
General disorders     
Vessel puncture site haematoma  1  2/58 (3.45%)  0/64 (0.00%) 
Infections and infestations     
Nasopharyngitis  1  2/58 (3.45%)  0/64 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  2/58 (3.45%)  2/64 (3.13%) 
Blood creatine phosphokinase increased  1  0/58 (0.00%)  2/64 (3.13%) 
Metabolism and nutrition disorders     
Gout  1  2/58 (3.45%)  0/64 (0.00%) 
Nervous system disorders     
Dizziness  1  4/58 (6.90%)  1/64 (1.56%) 
Headache  1  4/58 (6.90%)  1/64 (1.56%) 
Psychiatric disorders     
Insomnia  1  2/58 (3.45%)  0/64 (0.00%) 
Renal and urinary disorders     
Haematuria  1  4/58 (6.90%)  2/64 (3.13%) 
Vascular disorders     
Hypertension  1  2/58 (3.45%)  2/64 (3.13%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Health Science Center
Organization: The Medicines Company
Phone: 1-888-977-6326
EMail: medical.information@themedco.com
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT02678923    
Other Study ID Numbers: MDCO-APO-15-01
2015-000826-13 ( EudraCT Number )
First Submitted: February 5, 2016
First Posted: February 10, 2016
Results First Submitted: June 12, 2017
Results First Posted: July 13, 2017
Last Update Posted: July 13, 2017