A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab

Inclusion Criteria

• •Participant Eligibility Criteria
• •1. Participant must understand and sign the informed consent.
• •2. Participant must be 18 years of age or older.
• •3. Participant must have a diagnosis of VHL disease. In accordance with established criteria for diagnosis, any one of the following will be considered sufficient evidence that VHL disease is present:
• •* A family history of VHL disease plus one or more of the following lesions: RCH, spinal or cerebellar hemangioblastoma, pheochromocytoma, multiple pancreatic cysts, epididymal or broad ligament cystadenomas, multiple renal cysts or renal cell carcinoma before age 60 years.
• •* Presence of two or more hemangioblastomas of the retina or brain or a single hemangioblastoma in association with a visceral manifestation such as kidney or pancreatic cysts; renal cell carcinoma; adrenal or extra-adrenal pheochromocytomas; endolymphatic sac tumors; papillary cystadenomas of the epididymis or broad ligament; or neuroendocrine tumors of the pancreas.
• •* Presence of a known disease-causing germline mutation in the VHL gene.
• •4. Any female participant of childbearing potential must not be pregnant or breast-feeding, must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing immediately prior to each treatment.
• •5. Any female participant of childbearing potential and any male participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for at least two months following the last administration of combination investigational treatment. Acceptable methods of contraception include:
• •* hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
• •* intrauterine device,
• •* barrier methods (diaphragm or condom) with spermicide, or
• •* surgical sterilization (hysterectomy, tubal ligation or vasectomy).
• •1. Participant has at least one RCH secondary to VHL disease in the study eye that fulfills the following criteria:
• •1. The RCH must exhibit growth potential with consequent threat to vision. Growth potential with consequent threat to vision is defined by AT LEAST ONE of the following:
• •* Associated intra- or sub-retinal exudation or lipid deposition that, in the judgment of the investigator, reflects ongoing vascular incompetence and is not solely reflective of residual changes following previous treatment or solely secondary to coexistent retinal traction.
• •* Increased size of the tumor compared to a previous time point as assessed by fundus photography or FA.
• •* Associated intra-, sub- or pre-retinal hemorrhage not secondary to previous treatment, as assessed by fundus photography or FA.
• •* The presence of dilated and/or tortuous feeder vessels.
• •* Vitreous cell or haze indicative of vitreous exudation, in the absence of other ocular features potentially responsible for such findings.
• •2. The RCH, in the judgment of the investigator, is NOT readily treatable using thermal laser because of its size, posterior location, poor previous response to conventional therapy, association with significant exudation, epiretinal proliferation, associated vascular abnormalities such as vascular proliferation or diffusely incompetent retinal vessels, or other factors predictive of a poor response to standard of care approaches.
• •2. The study eye must have clarity of ocular media and degree of pupil dilation sufficient to permit adequate fundus photography.