99mTc-rhAnnexin V-128 Imaging for Carotid Atherosclerosis

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.

Time frame: 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.

Time frame: At 60 and 120 minutes post injection on Day 0

Population: Full Analysis Set population (FAS)

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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

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.

Time frame: 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.

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).

Time frame: 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.

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.

Time frame: From Day 0 post injection up to Day 30

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

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.

Time frame: From Day 0 post injection up to Day 30

Population: Safety Population Set

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.

Time frame: 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.

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).

Time frame: 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.