Trial Outcomes & Findings for 99mTc-rhAnnexin V-128 Imaging for Carotid Atherosclerosis (NCT NCT02667457)

NCT ID: NCT02667457

Last Updated: 2020-10-09

Results Overview

The frequency and severity of abnormal carotid scans was determined in the CAD participants and control groups by review of the number, localization, length and uptake intensity grade of each plaque to define a positive or negative scan at each time point. The feasibility of imaging apoptotic activity in CAD using 99mTc-rhAnnexin V-128 was assessed by the data monitoring committee (visual image review and consensus). The three reviewers of the DMC did an independent visual assessment of the images using a 1 to 4 point grading system: each observer reviewed the images of each patient and scored either 1 or 2 (uptake was less than or equal to blood pool), these images were considered normal; 3 was equivocal and four equalled abnormal. Only descriptive analysis performed.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 39 participants
• Primary outcome timeframe: Day 0
• Results posted on: 2020-10-09

Participant Flow

The study was conducted at single center in Canada.

A total of 39 participants were screened and enrolled to the study, of which only 36 participants were administered with investigational imaging product. All 36 treated participants completed the study.

Participant milestones

Measure	Carotid Atherosclerotic Plaque (CAD) Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an intraveneous (IV) catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Overall Study STARTED	27	12
Overall Study Dosed Participants	26	10
Overall Study Full Analysis Set Population (FAS)	25	10
Overall Study COMPLETED	26	10
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Carotid Atherosclerotic Plaque (CAD) Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an intraveneous (IV) catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Overall Study Withdrawal by Subject	1	0
Overall Study Other Reason	0	2

Baseline Characteristics

99mTc-rhAnnexin V-128 Imaging for Carotid Atherosclerosis

Baseline characteristics by cohort

Measure	CAD Participants n=26 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Total n=36 Participants Total of all reporting groups
Age, Continuous	70.9 years STANDARD_DEVIATION 6.6 • n=5 Participants	58.4 years STANDARD_DEVIATION 12.1 • n=7 Participants	67.4 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	5 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	26 Participants n=5 Participants	9 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0

Population: Full Analysis Set population (FAS)

The frequency and severity of abnormal carotid scans was determined in the CAD participants and control groups by review of the number, localization, length and uptake intensity grade of each plaque to define a positive or negative scan at each time point. The feasibility of imaging apoptotic activity in CAD using 99mTc-rhAnnexin V-128 was assessed by the data monitoring committee (visual image review and consensus). The three reviewers of the DMC did an independent visual assessment of the images using a 1 to 4 point grading system: each observer reviewed the images of each patient and scored either 1 or 2 (uptake was less than or equal to blood pool), these images were considered normal; 3 was equivocal and four equalled abnormal. Only descriptive analysis performed.

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Number of Participants Evaluated for Imaging Feasibility	15 Participants	5 Participants

PRIMARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set population (FAS)

The prevalence of apoptotic activity was defined as the percentage of participants with "abnormal" Single-Photon Emission Computed Tomography (SPECT) imaging scans (also described as positive scans). The overall result of 99mTc-rhAnnexin V-128 imaging was unique: participants with at least one SPECT imaging as positive result (after 60 min or after 120 min from 99mTc-rhAnnexin V-128 injection) were considered as abnormal, participants with SPECT/CT images as negative were considered as normal. All images were acquired with a dual head SPECT/CT gamma camera with low-energy high-resolution collimators. Only descriptive analysis performed.

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step) 60 mins after injection · Missing	1 Participants	0 Participants
Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step) 60 mins after injection · Positive (abnormal)	8 Participants	0 Participants
Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step) 60 mins after injection · Negative (normal)	16 Participants	10 Participants
Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step) 120 mins after injection · Positive (abnormal)	8 Participants	0 Participants
Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step) 120 mins after injection · Negative (normal)	17 Participants	10 Participants
Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step) 120 mins after injection · Missing	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with Left Carotid Uptake Imaging Assessment included in the analysis.

Quantitative analysis of planar images was carried out by placing a region of interest in the carotid areas and over a background area placed in the subclavian regions representing venous and arterial activity (target-to-background). Carotid artery uptake measured as TBR data for right and left carotids at 1 and 2 hours was compared between normal control and carotid artery disease groups.

Quantitative analysis of the SPECT 1 and 2 hour images was done with regions of interest placed over the arterial target (right carotid, left carotid, ascending aorta, arch and descending aorta) and adjacent vein (internal jugular, SVC or IVS) using transaxial slices. TBR was calculated as arterial max / venous mean (the average of 3 slices centered on the slice with the highest TBR value).

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Left Carotid Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 60 Minutes	1.171 Target to Background Ratio (TBR) Standard Deviation 0.764	0.697 Target to Background Ratio (TBR) Standard Deviation 0.222
Left Carotid Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 120 Minutes	1.208 Target to Background Ratio (TBR) Standard Deviation 0.486	0.827 Target to Background Ratio (TBR) Standard Deviation 0.205

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with Right Carotid Uptake Imaging Assessment included in the analysis.

Quantitative analysis of planar images was carried out by placing a region of interest in the carotid areas and over a background area placed in the subclavian regions representing venous and arterial activity (target-to-background). Carotid artery uptake measured as TBR data for right and left carotids at 1 and 2 hours was compared between normal control and carotid artery disease groups.

Quantitative analysis of the SPECT 1 and 2 hour images was done with regions of interest placed over the arterial target (right carotid, left carotid, ascending aorta, arch and descending aorta) and adjacent vein (internal jugular, SVC or IVS) using transaxial slices. TBR was calculated as arterial max / venous mean (the average of 3 slices centered on the slice with the highest TBR value).

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Right Carotid Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 60 Minutes	1.252 Target to Background Ratio (TBR) Standard Deviation 0.745	0.768 Target to Background Ratio (TBR) Standard Deviation 0.209
Right Carotid Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 120 Minutes	1.220 Target to Background Ratio (TBR) Standard Deviation 0.550	0.928 Target to Background Ratio (TBR) Standard Deviation 0.217

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with Ascending Aorta Uptake Imaging Assessment included in the analysis.

Quantitative analysis of planar images was carried out by placing a region of interest in the carotid areas and over a background area placed in the subclavian regions representing venous and arterial activity (target-to-background). Carotid artery uptake measured as TBR data for right and left carotids at 1 and 2 hours was compared between normal control and carotid artery disease groups.

Quantitative analysis of the SPECT 1 and 2 hour images was done with regions of interest placed over the arterial target (right carotid, left carotid, ascending aorta, arch and descending aorta) and adjacent vein (internal jugular, SVC or IVS) using transaxial slices. TBR was calculated as arterial max / venous mean (the average of 3 slices centered on the slice with the highest TBR value).

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Ascending Aorta Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 60 Minutes	2.054 Target to Background Ratio (TBR) Standard Deviation 0.656	1.574 Target to Background Ratio (TBR) Standard Deviation 0.252
Ascending Aorta Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 120 Minutes	1.616 Target to Background Ratio (TBR) Standard Deviation 0.294	1.381 Target to Background Ratio (TBR) Standard Deviation 0.190

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with Descending Aorta Uptake Imaging Assessment included in the analysis.

Quantitative analysis of planar images was carried out by placing a region of interest in the carotid areas and over a background area placed in the subclavian regions representing venous and arterial activity (target-to-background). Carotid artery uptake measured as TBR data for right and left carotids at 1 and 2 hours was compared between normal control and carotid artery disease groups.

Quantitative analysis of the SPECT 1 and 2 hour images was done with regions of interest placed over the arterial target (right carotid, left carotid, ascending aorta, arch and descending aorta) and adjacent vein (internal jugular, SVC or IVS) using transaxial slices. TBR was calculated as arterial max / venous mean (the average of 3 slices centered on the slice with the highest TBR value).

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Descending Aorta Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 60 Minutes	2.159 Target to Background Ratio (TBR) Standard Deviation 0.865	1.590 Target to Background Ratio (TBR) Standard Deviation 0.164
Descending Aorta Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR) 120 Minutes	1.520 Target to Background Ratio (TBR) Standard Deviation 0.245	1.341 Target to Background Ratio (TBR) Standard Deviation 0.131

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with Aortic Arch Uptake Correlation Imaging Assessment included in the analysis.

Quantitative analysis of planar images was carried out by placing a region of interest in the carotid areas and over a background area placed in the subclavian regions representing venous and arterial activity (target-to-background). Carotid artery uptake measured as TBR data for right and left carotids at 1 and 2 hours was compared between normal control and carotid artery disease groups.

Quantitative analysis of the SPECT 1 and 2 hour images was done with regions of interest placed over the arterial target (right carotid, left carotid, ascending aorta, arch and descending aorta) and adjacent vein (internal jugular, SVC or IVS) using transaxial slices. TBR was calculated as arterial max / venous mean (the average of 3 slices centered on the slice with the highest TBR value).

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Aortic Arch Uptake Correlation Imaging Assessment as Measured by Target to Background Ratio (TBR) 60 Minutes	1.986 Target to Background Ratio (TBR) Standard Deviation 0.679	1.606 Target to Background Ratio (TBR) Standard Deviation 0.279
Aortic Arch Uptake Correlation Imaging Assessment as Measured by Target to Background Ratio (TBR) 120 Minutes	1.628 Target to Background Ratio (TBR) Standard Deviation 0.380	1.294 Target to Background Ratio (TBR) Standard Deviation 0.174

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with left carotid with stenosis \>=50% are taken into account.

B-mode and color Doppler ultrasound studies were acquired of both carotid arteries and performed with an ultrasound scanner equipped with a 5- to 7-MHz transducer. Plaque morphology, as echogenicity, defined as reflectance of the emitted ultrasound signal, were assessed and graded from 1 to 4 as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. The vessel lumen was used as the reference structure for defining echolucency, and the bright echo zone produced by the media-adventitia interface in the far wall was used as the reference structure for defining echogenicity. Uptake was reported as the ratio of the uptake in the region of interest (target) to the uptake in the blood pool (background). Only descriptive analysis performed.

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Left Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echolucent: 60 Minutes	1.490 Ratio Standard Deviation 0.756	—
Left Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echolucent: 120 Minutes	1.014 Ratio Standard Deviation 0.309	—
Left Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echogenic: 60 Minutes	0.945 Ratio Standard Deviation 0.287	—
Left Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echogenic: 120 Minutes	1.096 Ratio Standard Deviation 0.186	—
Left Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Echogenic: 60 Minutes	0.950 Ratio Standard Deviation 0.245	—
Left Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Echogenic: 120 Minutes	1.387 Ratio Standard Deviation 0.496	—

SECONDARY outcome

Timeframe: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set (FAS). Only participants with right carotid with stenosis \>=50% are taken into account.

B-mode and color Doppler ultrasound studies were acquired of both carotid arteries and performed with an ultrasound scanner equipped with a 5- to 7-MHz transducer. Plaque morphology, as echogenicity, defined as reflectance of the emitted ultrasound signal, were assessed and graded from 1 to 4 as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. The vessel lumen was used as the reference structure for defining echolucency, and the bright echo zone produced by the media-adventitia interface in the far wall was used as the reference structure for defining echogenicity. Uptake was reported as the ratio of the uptake in the region of interest (target) to the uptake in the blood pool (background). Only descriptive analysis performed.

Outcome measures

Measure	CAD Participants n=25 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Echolucent: 60 Minutes	0.619 Ratio Standard Deviation 0.000	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Echolucent: 120 Minutes	0.820 Ratio Standard Deviation 0.000	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echolucent: 60 Minutes	0.955 Ratio Standard Deviation 0.192	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echolucent: 120 Minutes	1.126 Ratio Standard Deviation 0.311	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echogenic: 60 Minutes	1.593 Ratio Standard Deviation 1.174	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Predominantly echogenic: 120 Minutes	1.294 Ratio Standard Deviation 0.851	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Echogenic: 60 Minutes	1.180 Ratio Standard Deviation 0.206	—
Right Carotid Uptake Imaging Assessment as Measure by Target to Background Ratio (TBR) by Ultrasound Grade of Plaque Echolucency/Echogenicity Echogenic: 120 Minutes	1.149 Ratio Standard Deviation 0.438	—

SECONDARY outcome

Timeframe: From Day 0 post injection up to Day 30

Population: Safety Population Set

An AE is defined as any untoward medical occurrence in a participant and which does not necessarily have a causal relationship with the investigational product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease, temporally associated with the use of an investigational product, whether or not causally related to the investigational product. Treatment emergent adverse events that emerge after the 99mTc-rhAnnexin V-128 injection and up to 30 days after the injection that were absent before it or worsen relative to the pre-treatment state. A serious AE is defined as any untoward medical occurrence that at any dose results in death; is life-threatening; results in persistent or significant disability or incapacity; results in congenital anomaly or birth defect; or requires inpatient hospitalization or prolongation of hospitalization. Only descriptive analysis performed.

Outcome measures

Measure	CAD Participants n=26 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and Death TEAEs leading to Withdrawal	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and Death TEAEs leading to Deaths	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and Death Treatment Emergent Adverse Events (TEAEs)	7 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and Death Treatment Emergent Adverse Drug Reactions	2 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and Death Treatment Emergent Serious Adverse Events (TESAEs)	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and Death Treatment Emergent Serious Adverse Drug Reactions	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 0 post injection up to Day 30

Population: Safety Population Set. Only participants with abnormal laboratory values are taken into account.

Laboratory data was analysed with respect to the normal ranges of values provided by the local laboratory and with respect to levels of change and significance in these values. The evaluation of the "Clinically Significant Abnormal Laboratory Values" was at the discretion of the Principal Investigator and noted as such in patient files, where necessary. Participants with abnormal laboratory values were analyzed based on clinical relevance. Only descriptive analysis performed.

Outcome measures

Measure	CAD Participants n=26 Participants Participants with asymptomatic or previously symptomatic with TIA only carotid atherosclerotic plaque with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.	Healthy Participants n=10 Participants Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on Day 0.
Number of Participants With Clinically Significant Abnormal Laboratory Values Blood Chemistry · Abnormal non clinical relevant	26 Participants	10 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Blood Chemistry · Abnormal clinically relevant	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Hematology · Abnormal non clinical relevant	15 Participants	4 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Hematology · Abnormal clinically relevant	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Urinalysis · Abnormal non clinical relevant	10 Participants	4 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Urinalysis · Abnormal clinically relevant	0 Participants	0 Participants

Adverse Events

CAD Participants

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Healthy Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	CAD Participants n=26 participants at risk Participants with asymptomatic carotid atherosclerotic plaque or previously symptomatic with TIA only with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on screening (Day 0).	Healthy Participants n=10 participants at risk Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on screening (Day 0).
Cardiac disorders Bradycardia	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.

Other adverse events

Measure	CAD Participants n=26 participants at risk Participants with asymptomatic carotid atherosclerotic plaque or previously symptomatic with TIA only with evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on screening (Day 0).	Healthy Participants n=10 participants at risk Healthy participants with no significant carotid artery disease on carotid ultrasound, received a single intravenous bolus of 350 MBq ± 10 % of 99mTc-rhAnnexin V-128 via an IV catheter in an antecubital vein, followed by a saline flush on screening (Day 0).
Cardiac disorders Palpitations	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.
Injury, poisoning and procedural complications Accident	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 1/26 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.
Musculoskeletal and connective tissue disorders Muscle spasms	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.
Psychiatric disorders Claustrophobia	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.
Respiratory, thoracic and mediastinal disorders Sinus headache	3.8% 1/26 • Number of events 1 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.	0.00% 0/10 • Adverse events were collected from Day 0 up to Day 30 Analysis was performed in the safety population defined as all participants who received the administration of 99mTc-rhAnnexin V-128.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER