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

Phase 1
18 Years
65 Years
Not Enrolling
Choroidal Neovascularization, Degenerative Myopia, Pathological Myopia

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Trial Information

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

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.

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

each visit for study duration up to 24 mos

Safety Issue:


Principal Investigator

Quan D Nguyen, MD, MSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Food and Drug Administration

Study ID:

FVF 3687



Start Date:

June 2005

Completion Date:

May 2008

Related Keywords:

  • Choroidal Neovascularization
  • Degenerative Myopia
  • Pathological Myopia
  • Choroidal Neovascularization
  • Macular Degeneration
  • Myopia
  • Neovascularization, Pathologic
  • Myopia, Degenerative
  • Choroidal Neovascularization