Trial Outcomes & Findings for Effect of Evolocumab on Coronary Plaque Characteristics (NCT NCT04710368)
NCT ID: NCT04710368
Last Updated: 2023-11-18
Results Overview
Changes in the minimal Minimal Fibrous Cap Thickness (FCT) is assessed by Optical Coherence Tomography (OCT) imaging and measured in microns. FCT describes plaque morphology composition.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
137 participants
Primary outcome timeframe
Baseline and 26 Weeks
Results posted on
2023-11-18
Participant Flow
329 Patients were screened with 137 enrolled.
Participant milestones
| Measure |
Treatment
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Overall Study
STARTED
|
137
|
|
Overall Study
COMPLETED
|
110
|
|
Overall Study
NOT COMPLETED
|
27
|
Reasons for withdrawal
| Measure |
Treatment
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Lost to Follow-up
|
4
|
|
Overall Study
Death
|
2
|
|
Overall Study
Patient preference
|
11
|
|
Overall Study
Treatment discontinuation
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Treatment
n=137 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Age, Continuous
|
66.0 years
STANDARD_DEVIATION 9.7 • n=137 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=137 Participants
|
|
Sex: Female, Male
Male
|
98 Participants
n=137 Participants
|
|
Body Mass Index (BMI)
|
31.6 kg/m^2
STANDARD_DEVIATION 19.3 • n=137 Participants
|
|
Hypertension
|
127 Participants
n=137 Participants
|
|
Previous Percutaneous coronary intervention (PCI)
|
97 Participants
n=137 Participants
|
|
Previous Myocardial Infarction (MI)
|
32 Participants
n=137 Participants
|
|
Current smoking
|
14 Participants
n=137 Participants
|
|
History of smoking
|
51 Participants
n=137 Participants
|
|
Diabetes
|
74 Participants
n=137 Participants
|
|
Baseline statin use
High intensity
|
91 Participants
n=129 Participants • 8 statin intolerant patients
|
|
Baseline statin use
Moderate intensity
|
38 Participants
n=129 Participants • 8 statin intolerant patients
|
|
Baseline statin use
Low intensity
|
0 Participants
n=129 Participants • 8 statin intolerant patients
|
|
Diseased Coronary Vessel Type
LAD - Left Anterior Descending Artery
|
29 Participants
n=137 Participants
|
|
Diseased Coronary Vessel Type
LCX - Left Circumflex Artery
|
36 Participants
n=137 Participants
|
|
Diseased Coronary Vessel Type
RCA - Right Coronary Artery
|
70 Participants
n=137 Participants
|
|
Diseased Coronary Vessel Type
RI - Ramus Intermedius Artery
|
2 Participants
n=137 Participants
|
|
Number of diseased vessels
3
|
4 Participants
n=137 Participants
|
|
Number of diseased vessels
2
|
31 Participants
n=137 Participants
|
|
Number of diseased vessels
1
|
83 Participants
n=137 Participants
|
|
Number of diseased vessels
0
|
19 Participants
n=137 Participants
|
PRIMARY outcome
Timeframe: Baseline and 26 WeeksChanges in the minimal Minimal Fibrous Cap Thickness (FCT) is assessed by Optical Coherence Tomography (OCT) imaging and measured in microns. FCT describes plaque morphology composition.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Minimal Fibrous Cap Thickness (FCT)
Baseline
|
70.9 µm
Standard Deviation 21.7
|
|
Change in Minimal Fibrous Cap Thickness (FCT)
26 Weeks
|
97.7 µm
Standard Deviation 31.1
|
PRIMARY outcome
Timeframe: Baseline and 26 WeeksOutcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Number of Participants With FCT <65 µm
Baseline
|
53 Participants
|
|
Number of Participants With FCT <65 µm
26 weeks
|
14 Participants
|
PRIMARY outcome
Timeframe: 26 weeksOutcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Number of Participants With Increased Fibrous Cap
|
88 Participants
|
PRIMARY outcome
Timeframe: Baseline and 26 WeeksChanges in maximal lipid-core burden index within 4 mm (maxLCBI4mm). LCBI4mm is assessed by NIRS and calculated as the fraction of yellow pixels on a chemogram multiplied by 1000. Each pixel on the chemogram represents a probability of lipid presence in the given region; pixels are color-coded on a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Maximal lipid-core burden index is calculated as a fraction of yellow pixels (representing lipid) obtained from the NIRS chemogram multiplied by 1000. It ranges is from 0 to 1000 and represents the amount of lipid in the investigated segment with "0" corresponding to no lipid and "1000" representing all lipid lesion.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in maxNIRS4mm
Baseline
|
306.8 index
Standard Deviation 177.6
|
|
Change in maxNIRS4mm
26 Weeks
|
213.1 index
Standard Deviation 168.0
|
PRIMARY outcome
Timeframe: 26 WeeksOutcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Number of Participants With Decreased maxLCBI4mm
|
86 Participants
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksChange in Maximal lipid arc assessed by OCT and measured in degrees.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Maximal Lipid Arc
Baseline
|
189.1 degrees
Standard Deviation 73.4
|
|
Change in Maximal Lipid Arc
26 Weeks
|
161.6 degrees
Standard Deviation 68.7
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksChange in Lipid length by OCT, measured in millimeters.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Lipid Length
Baseline
|
10.4 mm
Standard Deviation 6.0
|
|
Change in Lipid Length
26 Weeks
|
8.9 mm
Standard Deviation 5.6
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksChange in Lipid Volume Length (LVI) calculated as the average lipid arc multiplied by lipid length assessed by OCT.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Lipid Volume Index (LVI)
Baseline
|
1259.4 mm*degrees
Standard Deviation 994.5
|
|
Change in Lipid Volume Index (LVI)
26 Weeks
|
972.0 mm*degrees
Standard Deviation 855.7
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksChange in the prevalence of Macrophage accumulation (maximum and average) by OCT, a marker of inflammation (expressed as frequency of the presence of macrophages in lesions.)
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Macrophage Accumulation
Average macrophage arc 26 Weeks
|
71.2 degrees
Standard Deviation 32.0
|
|
Change in Macrophage Accumulation
Maximum macrophage arc Baseline
|
148.2 degrees
Standard Deviation 72.5
|
|
Change in Macrophage Accumulation
Maximum macrophage arc 26 Weeks
|
122.1 degrees
Standard Deviation 67.7
|
|
Change in Macrophage Accumulation
Average macrophage arc Baseline
|
83.4 degrees
Standard Deviation 36.5
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksChange in the Macrophage Volume Index by OCT, a marker of inflammation (expressed as frequency of the presence of macrophages in lesions.)
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Macrophage Volume Index
Baseline
|
876.4 mm*degrees
Standard Deviation 757.6
|
|
Change in Macrophage Volume Index
26 Weeks
|
590.0 mm*degrees
Standard Deviation 557.3
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksOutcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Macrophage Length
Baseline
|
9.6 mm
Standard Deviation 5.7
|
|
Change in Macrophage Length
26 Weeks
|
7.6 mm
Standard Deviation 5.2
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksChange in Calcification accumulation by OCT expressed as frequency of the presence of calcification in lesions.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Calcification Accumulation
Maximum calcium arc Baseline
|
98.6 degrees
Standard Deviation 55.7
|
|
Change in Calcification Accumulation
Maximum calcium arc 26 Weeks
|
98.6 degrees
Standard Deviation 54.6
|
|
Change in Calcification Accumulation
Average calcium arc Baseline
|
61.1 degrees
Standard Deviation 26.1
|
|
Change in Calcification Accumulation
Average calcium arc 26 Weeks
|
61.2 degrees
Standard Deviation 25.1
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksOutcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Calcium Length
Baseline
|
6.4 mm
Standard Deviation 4.9
|
|
Change in Calcium Length
26 Weeks
|
6.7 mm
Standard Deviation 4.7
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksChange in PAV assessed by Intravascular Ultrasound (IVUS). PAV characterizes coronary plaque burden and calculated as the proportion of total vessel wall volume occupied by atherosclerotic plaque. The percent atheroma volume is calculated as the proportion of total vessel wall volume occupied by atherosclerotic plaque - plaque volume divided by vessel volume and multiplied by 100.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Percent Atheroma Volume (PAV)
Baseline
|
51.6 percent atheroma volume
Standard Deviation 8.9
|
|
Change in Percent Atheroma Volume (PAV)
26 Weeks
|
50.2 percent atheroma volume
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: Baseline and 26 WeeksChange in TAV assessed by IVUS. TAV characterizes the total volume of coronary plaque.
Outcome measures
| Measure |
Treatment
n=110 Participants
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Change in Total Atheroma Volume (TAV)
Baseline
|
137.2 mm^3
Standard Deviation 72.8
|
|
Change in Total Atheroma Volume (TAV)
26 Weeks
|
131.2 mm^3
Standard Deviation 71.8
|
SECONDARY outcome
Timeframe: Baseline and 1 yearChange in PBMC gene expression. Messenger RNA sequencing data will be processed using statistical and bioinformatics analyses.
Outcome measures
Outcome data not reported
Adverse Events
Treatment
Serious events: 5 serious events
Other events: 30 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Treatment
n=110 participants at risk
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Cardiac disorders
Myocardial Infarction
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Cardiac disorders
Urgent Revascularization
|
4.5%
5/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
Other adverse events
| Measure |
Treatment
n=110 participants at risk
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Evolocumab Injections: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
|
|---|---|
|
Cardiac disorders
Chest pain/tightness
|
10.0%
11/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Cardiac disorders
Shortness of breath
|
3.6%
4/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Cardiac disorders
Fatigue
|
3.6%
4/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Metabolism and nutrition disorders
Back/feet pain
|
2.7%
3/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Respiratory, thoracic and mediastinal disorders
Fever
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Eye disorders
Corneal abrasion
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Gastrointestinal disorders
Indigestion
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Respiratory, thoracic and mediastinal disorders
Cold/flu-like symptoms
|
1.8%
2/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Respiratory, thoracic and mediastinal disorders
COVID
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Vascular disorders
Groin Pain
|
4.5%
5/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Gastrointestinal disorders
Food poisoning
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Vascular disorders
Nose bleed
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Skin and subcutaneous tissue disorders
Papules
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Skin and subcutaneous tissue disorders
Hives
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
|
Cardiac disorders
Atrial Fibrillation
|
0.91%
1/110 • 6 months
Final AE will be reported at 12 months, October 2023 data still being collected
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place