99mTc-rhAnnexin V-128 Imaging for Carotid Atherosclerosis

NCT02667457 | Terminated Phase 2 Results DMC

• 2 other identifiers: AAA-Annexin-04CAAA113A32201
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This was a single-center, single-dose, study comprising a Proof of Concept (PoC) part and a subsequent Phase II part. The study was being done to assess the ability of the radiotracer 99mTc-rhAnnexin V-128 to image atherosclerotic plaque that might rupture and break off artery walls. This is caused by apoptosis or cell death in the plaque. These ruptured plaques can block blood circulation in the arteries causing a lack of oxygen to the tissues. Atherosclerotic plaques can build up on any artery in the body.

Conditions

Carotid Artery Plaque

Keywords

Carotid Stenosis; Carotid Artery Narrowing; Carotid Artery Plaque; Carotid Artery Stenosis; Carotid Artery Ulcerating Plaque; Carotid Ulcer; Common Carotid Artery Stenosis; External Carotid Artery Stenosis; Internal Carotid Artery Stenosis; Plaque, Ulcerating, Carotid Artery; Stenosis, Common Carotid Artery; Stenosis, External Carotid Artery; Ulcerating Plaque, Carotid Artery

Outcome Measures

Primary Outcomes (2)

• Number of Participants Evaluated for Imaging Feasibility

  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.

  Day 0

• Percentage of Participants With Prevalence of Abnormal 99mTc-rhAnnexin V-128 SPECT/CT Imaging (Phase II Step)

  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.

  At 60 and 120 minutes post injection on Day 0

Secondary Outcomes (9)

• Left Carotid Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR)

  At 60 and 120 minutes post injection on Day 0

• Right Carotid Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR)

  At 60 and 120 minutes post injection on Day 0

• Ascending Aorta Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR)

  At 60 and 120 minutes post injection on Day 0

• Descending Aorta Uptake Imaging Assessment as Measured by Target to Background Ratio (TBR)

  At 60 and 120 minutes post injection on Day 0

• Aortic Arch Uptake Correlation Imaging Assessment as Measured by Target to Background Ratio (TBR)

  At 60 and 120 minutes post injection on Day 0

Study Arms (2)

CAD Participants

EXPERIMENTAL

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 screening (Day 0).

Radiation: 99mTc-rhAnnexin V-128

Healthy Participants

EXPERIMENTAL

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).

Radiation: 99mTc-rhAnnexin V-128

Interventions

99mTc-rhAnnexin V-128 RADIATION

CAD Participants; Healthy Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all participants:
• Males and females age 18 years or greater
• Able and willing to comply with the study procedures
• Negative pregnancy test for women of childbearing potential at screening and on the day of administration of 99mTc-rhAnnexin V-128.
• For participants with carotid artery disease:
• Evidence of 50% or more carotid stenosis in one or more carotid arteries on carotid ultrasound within 2 years;
• Evidence of 50% or more carotid stenosis in the most recent US imaging within 8 weeks prior to 99mTc-rhAnnexin V-128 administration
• For control participants:
• No significant carotid artery disease on carotid ultrasound;
• No clinically significant abnormalities in baseline laboratory values.

You may not qualify if:

• Previous carotid stending, endarterectomy or stroke;
• Diagnosis of vasculitis, dissection, or non-atherosclerotic carotid disease (Ehlers-Danlos, Marfans);
• Pregnancy or lactation;
• History of any disease or relevant physical or psychiatric condition or abnormal physical finding which may interfere with the study objectives at the investigator judgment;
• Know hypersensitivity to the investigational product or any of its components;
• Claustrophobia or inability to lie still in a supine position;
• Unwillingness to provide consent.

Sponsors & Collaborators

• Advanced Accelerator Applications: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

MeSH Terms

Conditions

Carotid Stenosis

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

The study was prematurely terminated on 19-Mar-2019 due to strategic decisions to focus the AAA development portfolio on oncology theragnostics, and not based on any safety concerns.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: January 29, 2016
• Study Start: June 23, 2016
• Primary Completion: November 12, 2018
• Study Completion: November 19, 2018
• Last Updated: October 9, 2020
• Results First Posted: October 9, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)