Trial Outcomes & Findings for 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 (NCT NCT02678923)
NCT ID: NCT02678923
Last Updated: 2017-07-13
Results Overview
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.
COMPLETED
PHASE1/PHASE2
126 participants
Baseline, Day 36
2017-07-13
Participant Flow
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).
Participant milestones
| Measure |
MDCO-216
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
|
Placebo
360 mL of placebo (0.9% sodium chloride \[NaCl\] solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Overall Study
STARTED
|
59
|
67
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
58
|
64
|
|
Overall Study
mITT Population
|
52
|
61
|
|
Overall Study
COMPLETED
|
53
|
62
|
|
Overall Study
NOT COMPLETED
|
6
|
5
|
Reasons for withdrawal
| Measure |
MDCO-216
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
|
Placebo
360 mL of placebo (0.9% sodium chloride \[NaCl\] solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Overall Study
Protocol Deviation (Not Dosed)
|
1
|
3
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Did Not Return for Study Visits
|
1
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
MDCO-216
n=58 Participants
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=64 Participants
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
Total
n=122 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.2 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
61.4 years
STANDARD_DEVIATION 10.3 • n=7 Participants
|
61.8 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
56 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
38 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 36Population: 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.
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.
Outcome measures
| Measure |
MDCO-216
n=52 Participants
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=61 Participants
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Change From Baseline In Percent Atheroma Volume (PAV) At Day 36
|
-0.21 change in percent
Standard Error 0.386
|
-0.94 change in percent
Standard Error 0.382
|
SECONDARY outcome
Timeframe: Baseline, Day 36Population: 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.
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.
Outcome measures
| Measure |
MDCO-216
n=52 Participants
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=61 Participants
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Change From Baseline In Total Atheroma Volume (TAV) At Day 36
|
-6.33 cubic millimeter (mm^3)
Standard Error 3.425
|
-7.89 cubic millimeter (mm^3)
Standard Error 3.354
|
SECONDARY outcome
Timeframe: Baseline, Day 36Population: 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.
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.
Outcome measures
| Measure |
MDCO-216
n=52 Participants
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=61 Participants
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Change From Baseline In TAV For The 10 Millimeters (mm) Subsegment With The Greatest Disease Burden At Day 36
|
-2.16 mm^3
Standard Error 1.809
|
-1.74 mm^3
Standard Error 1.908
|
SECONDARY outcome
Timeframe: Baseline through Day 36Population: 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.
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.
Outcome measures
| Measure |
MDCO-216
n=52 Participants
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=61 Participants
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change Greater Than 2 Standard Deviations Of Test-Retest Measurement Variability
|
NA participants
Test-retest requires IVUS to be done twice at the same time point and retest IVUS was not done.
|
NA participants
Test-retest requires IVUS to be done twice at the same time point and retest IVUS was not done.
|
SECONDARY outcome
Timeframe: Baseline through Day 36Population: 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.
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.
Outcome measures
| Measure |
MDCO-216
n=52 Participants
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=61 Participants
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Participants With Regression Of Coronary Atherosclerosis As Measured By A PAV Change <0
|
29 Participants
|
41 Participants
|
Adverse Events
MDCO-216
Placebo
Serious adverse events
| Measure |
MDCO-216
n=58 participants at risk
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=64 participants at risk
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Cardiac disorders
Angina unstable
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Cardiac disorders
Atrial flutter
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Cardiac disorders
Coronary artery disease
|
5.2%
3/58 • Up to 59 days (±2 days) post randomization
|
3.1%
2/64 • Up to 59 days (±2 days) post randomization
|
|
Cardiac disorders
Ventricular extrasystoles
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
General disorders
Vessel puncture site haemorrhage
|
0.00%
0/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Hepatobiliary disorders
Hepatitis acute
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Infections and infestations
Urinary tract infection
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Injury, poisoning and procedural complications
Coronary artery restenosis
|
0.00%
0/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
Investigations
Echocardiogram abnormal
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Nervous system disorders
Syncope
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
Vascular disorders
Deep vein thrombosis
|
1.7%
1/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
Other adverse events
| Measure |
MDCO-216
n=58 participants at risk
20 mg/kg of MDCO-216 administered IV as a 360 mL infusion over 2 hours on Days 1, 8, 15, 22, and 29
|
Placebo
n=64 participants at risk
360 mL of placebo (0.9% NaCl solution) infusion, IV, over 2 hours on Days 1, 8, 15, 22, and 29
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.2%
3/58 • Up to 59 days (±2 days) post randomization
|
6.2%
4/64 • Up to 59 days (±2 days) post randomization
|
|
Cardiac disorders
Bradycardia
|
5.2%
3/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
General disorders
Vessel puncture site haematoma
|
3.4%
2/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Infections and infestations
Nasopharyngitis
|
3.4%
2/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Investigations
Alanine aminotransferase increased
|
3.4%
2/58 • Up to 59 days (±2 days) post randomization
|
3.1%
2/64 • Up to 59 days (±2 days) post randomization
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/58 • Up to 59 days (±2 days) post randomization
|
3.1%
2/64 • Up to 59 days (±2 days) post randomization
|
|
Metabolism and nutrition disorders
Gout
|
3.4%
2/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Nervous system disorders
Dizziness
|
6.9%
4/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
Nervous system disorders
Headache
|
6.9%
4/58 • Up to 59 days (±2 days) post randomization
|
1.6%
1/64 • Up to 59 days (±2 days) post randomization
|
|
Psychiatric disorders
Insomnia
|
3.4%
2/58 • Up to 59 days (±2 days) post randomization
|
0.00%
0/64 • Up to 59 days (±2 days) post randomization
|
|
Renal and urinary disorders
Haematuria
|
6.9%
4/58 • Up to 59 days (±2 days) post randomization
|
3.1%
2/64 • Up to 59 days (±2 days) post randomization
|
|
Vascular disorders
Hypertension
|
3.4%
2/58 • Up to 59 days (±2 days) post randomization
|
3.1%
2/64 • Up to 59 days (±2 days) post randomization
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place