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Pilot Study of Intravitreal Injection of Ranibizumab (rhuFAB V2) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease

Phase 1
18 Years
Not Enrolling
Von Hippel-Lindau Syndrome

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Trial Information

Pilot Study of Intravitreal Injection of Ranibizumab (rhuFAB V2) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease

Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant heritable disorder in which
multiple benign and malignant neoplasms and cysts of specific histopathologies develop in
the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis, and
broad ligament. Retinal angioma may be one of the earliest manifestations of VHL disease and
may lead to a significant decrease in visual acuity of the affected individual. These tumors
rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically
macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on
or around the optic disk. Treatment of retinal angiomas depends on the location and size of
the lesions but typically consists of photocoagulation or cryotherapy. However, there is no
proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic
nerve or lesions in the peripheral retina too large to respond to the traditional therapies.
The genetic mutation found in VHL disease up-regulates the production of vascular
endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well
as others found elsewhere in the body show marked increase in VEGF. This open-label study
will pilot the use of an anti-VEGF therapy, ranibizumab (rhuFab V2) in 5 participants to
investigate the potential efficacy as a treatment for retinal angiomas associated with VHL.
Participants will receive 7 intravitreal injections of study drug over a 6 month period,
with the option of up to seven additional injections at the same dose and schedule during
follow-up for a maximum period of 1 year after the initiation of treatment. The primary
outcome will be a change in the best corrected visual acuity of 15 letters or more eight
weeks after a participant receives the final study injection. The secondary outcomes will be
a reduction in retinal thickening and leakage eight weeks after the participants receives
the final study injection, and adverse events including local and systemic toxicities.

Inclusion Criteria


1. Participant must understand and sign the informed consent.

2. Participant must be at least 18 years of age.

3. Participant must have retinal angiomas secondary to VHL in one or both eyes.

4. Participant must have either optic nerve tumors or peripheral tumors that have
caused central vision loss of 20/40 or worse.

5. Participant must have clear ocular media and adequate papillary dilation to
permit good quality stereoscopic fundus photography.

6. All women of childbearing potential must have a negative urine pregnancy test at
baseline, and be willing to undergo urine pregnancy testing immediately prior to
each injection, and monthly for at least 2 months following the last dose of

7. Women of child-bearing potential who are sexually active and men who are
sexually active are required to use two forms of birth control during the course
of the study.


1. History (within past 5 years) or evidence of severe cardiac disease (apparent in
electrocardiogram abnormalities, clinical history of unstable angina, acute coronary
syndrome, myocardial infarction, revascularization procedure within 6 months prior to
baseline, atrial or ventricular tachyarrythmias requiring ongoing treatment).

2. History of stroke within 12 months of study entry.

3. History within the past five years of a chronic ocular or periocular infection
(including any history of ocular herpes zoster).

4. Current acute ocular or periocular infection.

5. Any major surgical procedure within one month of study entry.

6. Known serious allergies to fluorescein dye.

7. Previous participation in a clinical trial (for either eye) involving anti-angiogenic
drugs (pegaptanib, ranibizumab, anecortave acetate, Protein Kinase C inhibitors,

8. Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or
device implantation) in the study eye.

9. History of vitrectomy surgery in the study eye.

10. History of glaucoma filtering surgery in the study eye.

11. History of corneal transplant in the study eye.

Type of Study:


Study Design:

Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

August 2004

Completion Date:

August 2007

Related Keywords:

  • Von Hippel-lindau Syndrome
  • Retinal Angioma
  • Tumor
  • Anti-VEGF
  • Monoclonal Antibody
  • Macular Edema
  • Von Hippel-Lindau Disease
  • VEGF
  • Ranibizumab
  • VHL
  • Von Hippel-Lindau Disease



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