Clinical Trial: Pilot Study of Intravitreal Injection of Ranibizumab (rhuFAB) for Advanced Ocular Disease of Von Hippel-Lindau Disease


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Sponsored by:	National Eye Institute (NEI)
Information provided by:	Warren G Magnuson Clinical Center (CC)

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 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 at 1 year. The secondary outcomes will be a reduction in retinal thickening and leakage at one year, and adverse events including local and systemic toxicities.

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

Treatment or Intervention	Phase
Drug: Ranibizumab	Phase I

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 serum pregnancy test at baseline, and be willing to undergo testing immediately prior to each injection, and monthly for at least 2 months following the last dose of ranibizumab. This can be done on urine testing.
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.
EXCLUSION CRITERIA:
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 or current acute ocular or periocular infection (including any history of ocular herpes zoster).
4. Any major surgical procedure within one month of study entry.
5. Known serious allergies to fluorescein dye.
6. Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, Protein Kinase C inhibitors, etc).
7. Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye.
8. History of vitrectomy surgery in the study eye.
9. History of glaucoma filtering surgery in the study eye.
10. History of corneal transplant in the study eye.