Ranibizumab Injections to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome

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Brief Title

Ranibizumab Injections to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome

Official Title

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

Brief Summary

      This study will examine whether he drug ranibizumab can slow or stop the growth of angiomas
      (blood vessel tumors) in patients with Von Hippel-Lindau syndrome (VHL). Angiomas commonly
      develop in the back of the eye on the retina and the optic nerve in patients with VHL.
      Although these tumors are not cancerous, they may cause significant vision loss. Current
      treatments, including laser therapy, cryotherapy, and vitrectomy, may not be successful or
      possible for all patients. Ranibizumab decreases production of VEGF, a growth factor that is
      important for the formation of new blood vessels and that is elevated in patients with VHL.
      Preliminary findings from other studies suggest that ranibizumab can reduce retinal
      thickening caused by vessel and tumor growth and improve vision.

      Patients 18 years of age and older with retinal angiomas due to VHL in one or both eyes and
      central vision loss of 20/40 or worse may be eligible for this study. Participants undergo
      the following tests and procedures:

        -  Medical history, physical examination, electrocardiogram (EKG) and blood tests.

        -  Eye examination, including eye pressure measurement and dilation of the pupils to
           examine the retina.

        -  Fluorescein angiography to evaluate the eye's blood vessels. For this test, a yellow dye
           is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of
           the retina are taken using a camera that flashes a blue light into the eye. The pictures
           show if any dye has leaked from the vessels into the retina, indicating possible blood
           vessel abnormality.

        -  Optical coherence tomography to measure retinal thickness. The eyes are examined through
           a machine that produces cross-sectional pictures of the retina. These measures are
           repeated during the study to determine changes, if any, in retinal thickening.

        -  Stereoscopic color fundus photography to examine the back of the eye. The pupils are
           dilated with eye drops to examine and photograph the back of the eye.

        -  Electroretinogram (ERG) to measure electrical responses generated from within the
           retina. For this test, the patient sits in a dark room for 30 minutes with his or her
           eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye
           patches are removed, the surface of the eye is numbed with eye drops, and contact lenses
           are placed on the eyes. The patient looks inside an open white globe that emits a series
           of light flashes for about 20 minutes. The contact lenses sense small electrical signals
           generated by the retina when the light flashes.

        -  Ranibizumab injections to treat ocular angiomas. Ranibizumab is injected through a
           needle into the eye's vitreous (gel-like substance that fills the inside of the eye).
           Seven injections are given over a 28-week period. Before each injection, the surface of
           the eye is numbed with anesthetic eye drops. This is followed by injection of another
           anesthetic into the lower portion of the eye in the clear tissue surrounding the white
           of the eye. After a few minutes, the ranibizumab is injected into the vitreous. Patients
           receive ranibizumab injections at the first visit (during enrollment) and again at 4, 8,
           12, 16, 20 and 24 weeks after the first injection. At the 28-week visit, the doctor will
           determine if further treatment is needed. Patients can continue to have injections every
           4 weeks until 1 year of follow-up (54 weeks).

      At each injection visit, participants repeat most of the tests described above to evaluate
      the response to treatment and return a week later for another eye examination.
    

Detailed Description

      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.
    

Study Phase

Phase 1

Study Type

Interventional




Condition

Von Hippel-Lindau Syndrome

Intervention

Ranibizumab


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

5

Start Date

August 10, 2004

Completion Date

August 15, 2007


Eligibility Criteria

        -  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
                  ranibizumab.

               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 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, etc).

          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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00089765

Organization ID

040240

Secondary IDs

04-EI-0240


Study Sponsor

National Eye Institute (NEI)


Study Sponsor

, , 


Verification Date

August 15, 2007