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Pilot Study of Intravitreal Injection of EYE001 (Anti-VEGF Pegylated Aptamer) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease

Phase 1
Not Enrolling
Hippel-Lindau Disease

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Trial Information

Pilot Study of Intravitreal Injection of EYE001 (Anti-VEGF Pegylated Aptamer) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease

Von Hippel-Lindau (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 anti-VEGF therapy (EYE001) in 5 patients to investigate the potential
efficacy as a treatment for retinal angiomas associated with VHL. Patients will receive 6
intravitreal injections of study drug over a 30-week period, then return for a follow-up
visit 1 year after initiating injections. The primary outcomes will be improvement in best
corrected visual acuity of 15 letters or more at 1 year, reduction in retinal thickening and
leakage at one year, changes in ERG amplitude and implicit time, and adverse events
including local and systemic toxicities.

Inclusion Criteria


Patient must understand and sign the informed consent.

Patient must be at least 18 years of age.

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

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

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

Patients must be post menopausal, surgically sterile for at least 12 months prior to study
entry, or agree to use at least two effective forms of birth control.

All women of childbearing potential must have a negative serum pregnancy test at baseline
and immediately prior to each injection and for at least 60 days following the last dose
of EYE001.

Patient must have lab values indicative of adequate hematological function (hemoglobin
greater than or equal to 10 g/dl, platelet count less than or equal to 130 x 10(9)/I, WBC
3.8-10.8 x 10(9)/I) within one month of baseline.

Patients must have lab values indicative of adequate liver function (serum bilirubin less
than or equal to 1.5 mg/dl, SGOT/ALT, SGPT/AST, GGT and alkaline phosphotase within 2 x
ULN) within one month of baseline.

Patients must have lab values indicative of adequate renal function serum creatinine less
than or equal to 2.0 mg/dl and BUN within 2.0 x ULN within one month of baseline.


Significant media opacities, including cataract that precludes quality fundus photographs
of the posterior pole.

History or evidence of severe cardiac disease (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).

History of stroke within 12 months of study entry.

History of or current acute ocular or periocular infection (including any history of
ocular herpes zoster).

Any major surgical procedure within one month of study entry.

Known serious allergies to fluorescein dye.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

March 2003

Completion Date:

November 2005

Related Keywords:

  • Hippel-Lindau Disease
  • Vision Loss
  • Optic Nerve Tumors
  • Macular Edema
  • Von Hippel-Lindau Disease
  • VEGF
  • EYE001
  • VHL
  • Von Hippel-Lindau Disease



National Eye Institute (NEI) Bethesda, Maryland  20892