The Use of Anti-CD4 mAb-Fragment for Imaging of Local Inflammation in Patients With Carotid Artery Stenosis

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2012 by Technische Universität Dresden
Sponsor:
Collaborator:
Klinikum Chemnitz gGmbH
Information provided by (Responsible Party):
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT00904254
First received: May 18, 2009
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

The primary objective of this study is to proof the concept of EP 1645 as a diagnostic tool for carotid artery atherosclerosis and plaque instability and to assess the safety and tolerability of this diagnostic agent, a monoclonal antibody fragment (Fab') conjugated with the diagnostic radionuclide 99mTc. Safety and tolerability will be determined by adverse events (AEs) observed and reported upon administration of the product and the absorbed dose of radiation.


Condition Intervention Phase
Carotid Stenosis
Radiation: EP 1645/Solution For Injection, 99mTC
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Use of Anti-CD4 mAb-Fragment for Imaging of Local Inflammation in Patients With Asymptomatic and Symptomatic Carotid Artery Stenosis - an Open Proof of Concept Study.

Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • Scintigraphic confirmation of clinical disease [ Time Frame: A total of 16 patients will be recruited for this study. ] [ Designated as safety issue: No ]
    8 patients with stable atherosclerosis will be assigned to study group 1 and 8 patients with instable atherosclerosis will be assigned to study group 2. It is expected that the study substance enriches only in carotid arteries of patients assigned to study group 2 and not in lesions of patients assigned to group 1. The study results of this proof-of-concept-study will be compared purely with descriptive methods in order to create a consistent set data which can be used for a valid case number estimation for a future phase II trial.


Secondary Outcome Measures:
  • Adverse events (signs and symptoms), laboratory tests. [ Time Frame: during the entire study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 21
Study Start Date: January 2015
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1, diagnostic comparison
EP 1645/Solution For Injection
Radiation: EP 1645/Solution For Injection, 99mTC
(Fab-fragment of Anti-human CD4,technetium-99m)
Other Name: CD4 Antibody

Detailed Description:

For the evaluation of atherosclerosis in carotid arteries up to now sonographic measurements of plaque burden are used. This method has advantages for investigation of carotid arteries since this region is easy accessible for this investigation. However, it does not allow evaluation of the vessels which are remote from the body surface, as, for instance, coronary arteries. A method for non-invasive reliable evaluation of such arteries is needed. Also the distinction between vulnerable and stable plaque has a great clinical relevance. A quantifiable method for the determination of the effects of new therapeutic approaches would be highly appreciated.

It is expected, that the new antibody fragment with its radioactive linkage will allow displaying an image of the activity distribution of the disease. Due to the fact that only patients with atherosclerotic changes in carotid arteries allow comparing the activity and the clinical signs of disease, this proof of concept study (phase II study) will be performed in patients with asymptomatic and symptomatic carotid artery stenosis.

  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male and female with either symptomatic (> 60%) or asymptomatic (> 80%) carotid artery stenosis between 50 and 80 years of age
  • Symptomatic stenosis of the A. carotis interna is defined as occurence of focal ischemic symptoms in the area of the supplying vessel, occurence of a transischemic attack (TIA), occurence of focal neurologic dysfunction or unilateral blindness.
  • informed consent in accordance with ICH GCP and § 40 AMG and StrahlSchV
  • sonography status from the patient is present (printout is available)
  • patients available for carotid surgery within 3 months after diagnosis of carotid artery stenosis
  • In patients with bilateral disease, only the stenosis considered for surgery will be included in the endpoint evaluation.

Exclusion Criteria:

  • patients > 80 years
  • major disease of the cardiovascular system, respiratory system, hepatobiliary system or CNS, which prevents patients from the study participation as to the opinion of the investigator
  • hepatic (transaminases > 3 x norm) or renal (serum creatinine increase > 2x norm) insufficiency
  • regular drug intake of biologics. Intake of all other drugs must be judged by investigator and must be the strictly documented
  • previous administration of xenogenous proteins
  • history of anaphylactic reaction to any drug administered by a parenteral pathway
  • previous participation in a radiopharmaceutical drug trial (unless the effective dose acquired by participation in the current trial will remain below 10 mSv)
  • participation in any clinical drug trial within 3 months prior to enrolment
  • women of child-bearing potential (child-bearing potential to be ruled out by one of the following: at least 2 years past menopause, hysterectomy, bilateral oophorectomy, bilateral tubal ligation)
  • Patients presenting clinical signs of severe systemic infection (CRP > 50 mg/dl)
  • Carotid Surgery (TEA) not possible within a time frame of 7 days after imaging
  • Patients with bilateral carotid stenosis if clinically regarded as critical by the angiologists.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00904254

Contacts
Contact: Joachim Siegert, MD, PhD +49 351 458 5694 joachim.siegert@mailbox.tu-dresden.de

Sponsors and Collaborators
Technische Universität Dresden
Klinikum Chemnitz gGmbH
Investigators
Principal Investigator: Christoph Schindler Schindler, MD Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden
  More Information

No publications provided

Responsible Party: Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT00904254     History of Changes
Other Study ID Numbers: TUD-Athero-040, 2008-008443-14
Study First Received: May 18, 2009
Last Updated: February 2, 2012
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Technische Universität Dresden:
symptomatic carotid artery stenosis
asymptomatic carotid artery stenosis
cerebrovascular disorders
monoclonal antibody
diagnostics
molecular target
immunoglobulin Fab fragments
physiological effects of drugs
Tc99m-pertechnetate
Fab-fragment of Anti-human CD4
Antibodies, Monoclonal
Antibodies

Additional relevant MeSH terms:
Carotid Stenosis
Constriction, Pathologic
Inflammation
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Pathologic Processes
Antibodies
Immunoglobulin Fab Fragments
Pharmaceutical Solutions
Physiological Effects of Drugs
Immunologic Factors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014