Bevicizumab (Avastin) Infusion for Choroidal Neovascularization (CNV) Not Associated With Age-Related Macular Degeneration (AMD)

February 2, 2009 updated by: Johns Hopkins University

An Open-Label, Pilot Study of Bevacizumab in Subjects With Choroidal Neovascularization Secondary to Diseases Other Than Age-Related Macular Degeneration

The purpose of this study is to see if the drug bevacizumab is safe and effective to use for people with choroidal neovascularization (CNV). CNV is an eye condition where abnormal blood vessels grow in the part of the eye responsible for central (straight ahead) vision. The drug is produced using recombinant DNA technology and has been approved by the FDA for use in colon cancer. Although not yet approved for people with CNV, the FDA has given permission to use this drug in this study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Bevacizumab is a recombinant humanized monoclonal antibody against VEGF. It has been approved by the FDA for the treatment of metastatic colon cancer 18. We hypothesize that VEGF also plays a role in the development of CNV in pathologic myopia. Therefore, employing a mode of therapy that would decrease the risks posed to eyes with attenuated sclera, we have treated, through special approval by the Pharmacy and Therapeutic Committee of the Johns Hopkins University School of Medicine, two patients with persistent myopic CNV with intravenous bevacizumab 19. Despite multiple treatments with PDT, the CNV remained active and vision continued to decline in these two index patients. After four infusions of bevacizumab, the CNV became inactive. Six months after the last infusion in each patient, the CNV showed no evidence of activity or leakage on fluorescein angiography. Vision also improved in the diseased eyes of both patients. The two patients tolerated the infusions well, with no adverse events detected. In particular, blood pressure remained stable and no proteinuria was noted on serial analyses of 24-hour urine collections. The Bascom Palmer Eye Institute at the University of Miami has also recently reported favorable outcomes of bevacizumab administered in repeated doses to 14 patients (age > 65 years) with CNV secondary to AMD that has been refractory to other therapies.

We propose a non-randomized, open-label pilot study to evaluate the effect of bevacizumab in patients with CNV due to any cause other than AMD. This design will allow us to closely monitor safety and tolerability of bevacizumab while we evaluate 3 bioactivity outcomes. Based upon dramatic responses in two patients with CNV due to myopic degeneration, we hypothesize that treatment with bevacizumab may have major advantages over current standard of care.

Study Type

Interventional

Enrollment

10

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Abbreviated: Contact Coordinator or Principal investigator for expanded criteria.

Inclusion Criteria:) Subfoveal CNV in study eye due to cause other than AMD. Best corrected visual acuity of 20/30 or less in study eye. Evidence of retinal thickening or subretinal fluid by OCT in study eye. Must be fluorescein leakage due to CNV in the study eye. If the CNV is a complication of another disease (i.e. uveitis), the disease must be under stabilization for at least 3 months prior to enrollment.

(ECG)at least 28 days prior to entry into the study must show no evidence of current or prior myocardial ischemia, infarction, or significant arrhythmia.

Adequate bone marrow function:

Absolute granulocyte count (neutrophils and bands) > 1500 cells/mm3;

  1. Platelet count > 100,000 cells/mm3;
  2. 9.0 g/dL; 9) PT/PTT within the institution upper limit of Hemoglobin, normal (ULN) or INR <1.1. 10) Adequate renal function: serum creatinine ≤ 2.0 mg/dL. 11)Patients of child bearing potential must abstain from sexual intercourse or use effective birth control. Negative serum pregnancy test result confirmation prior to treatment.

Patients must be able to return for all study visits within required visit windows.

Patients must provide written informed consent

- Exclusion Criteria:

  1. Previous subfoveal thermal laser therapy.
  2. Significant scarring or atrophy in the fovea that indicates substantial irreversible vision loss.
  3. Significant media opacities, including cataract, which can interfere with visual acuity, assessment of toxicity, or fundus photography.
  4. Any intraocular surgery in the study eye within 12 weeks of entry.
  5. If the CNV in the study eye has been treated with photodynamic therapy (PDT), the treatment must be at least 12 weeks prior to study entry, unless it is judged by the investigator that the ocular disease has deteriorated within the 12-week period
  6. Any treatment for CNV in the study eye with anti-vascular endothelial growth factor (anti-VEGF) therapy, intraocularly or intravenously, must be at least 6 weeks prior to study entry, unless it is judged that the ocular disease has deteriorated within the 6-week period
  7. Uncontrolled hypertension defined as blood pressure consistently (at 3 or more consecutive visits) greater than 150/100 irrespective or medication.
  8. Any history, physical signs, or EKG findings suggesting significant heart disease.
  9. History of thromboembolism or stroke.
  10. History, physical signs, or laboratory of bleeding diathesis or coagulopathy. Any history (within 3 years) of significant gastrointestinal, oral (gum), or nasal bleeding..
  11. History or physical signs of peripheral vascular disease.
  12. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to entry.
  13. Anticipation of need for major surgical procedure during the course of the study.
  14. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to entry.
  15. Women who are pregnant (positive pregnancy test) or breastfeeding.
  16. Protein concentration in a 24-hour urine specimen more than 1.3 x ULN.
  17. History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to entry.
  18. Serious, non-healing wound, ulcer, or bone fracture.
  19. Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, cavitation, or history of hemoptysis.
  20. Inability to comply with study and/or follow-up procedures.
  21. Any patient who is on standard anticoagulant therapy [INR targeted at 2.0 to 3.0] or treatment for deep vein thrombosis, or grade 3 or 4 venous thrombosis (Table 1), is not eligible to enroll in the study. Patients who are on stable, low-dose heparin or warfarin therapy may be eligible for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Visual acuity: In this pilot study, the sample size is not powered for clinical response. However, preliminary data on visual acuity will aid in the design of future randomized control trial.
Time Frame: each visit for study duration up to 24 mos
each visit for study duration up to 24 mos

Secondary Outcome Measures

Outcome Measure
Time Frame
Retinal thickness assessed by OCT
Time Frame: each visit
each visit
CNV leakage assessed by Digital Fluorescein Angiography
Time Frame: per protocol
per protocol

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (ACTUAL)

April 1, 2007

Study Completion (ACTUAL)

May 1, 2008

Study Registration Dates

First Submitted

December 1, 2006

First Submitted That Met QC Criteria

December 1, 2006

First Posted (ESTIMATE)

December 5, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

February 3, 2009

Last Update Submitted That Met QC Criteria

February 2, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FVF 3687
  • 05-05-16-06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Choroidal Neovascularization

Clinical Trials on Bevacizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kyrgyzstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe