Study of 2.0 mg Ranibizumab in Subjects With Ischemic Central Retinal Vein Occlusion (RAVE2)
Condition: Ischemia; Retinal Vein Occlusion; Pathologic Processes; Retinal Diseases; Eye Diseases
MeSH terms: Eye Diseases; Retinal Vein Occlusion; Retinal Diseases; Ischemia; Pathologic Processes
Intervention: ranibizumab
Intervention description: Ranibizumab is formulated as a sterile solution aseptically filled in a sterile 3-mL stoppered glass vial. Each vial contains 0.5 mL of 40 mg/mL (2.0-mg dose level) ranibizumab aqueous solution.
Intervention MeSH terms: Ranibizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Ischemic; Central; Retinal; Vein; Occlusion; Ranibizumab; Lucentis; CRVO; ISCRVO

Summary:

      The RAVE 2 trial is a phase I, open label, 12-month trial of intravitreal ranibizumab 2.0 mg
      in patients with ischemic CRVO who have been either previously treated with ranibizumab or
      treatment naïve.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects will be eligible if the following criteria are met:

               -  Ability to provide written informed consent and comply with study assessments for
                  the full duration of the study

               -  Age > 18 years

               -  For patients previously treated with ITV ranibizumab (Cohort 1):

               -  6 or more intravitreal injections of ranibizumab with presence of persistent
                  edema after a minimum of 6 ranibizumab injections followed in RAVE 1.

               -  For treatment naïve (Cohort 2):

               -  Ischemic CRVO within 3 months of enrollment as per the following inclusion
                  criteria

        Three of the following clinical tests must be present to demonstrate ischemic CRVO:

          -  VA 20/200 or worse

          -  RAPD 0.9 LU or worse

          -  Loss of 1-2e isopter on Goldmann Visual field (Kwon et al. 2001)

          -  ERG demonstrating b wave amplitude less than 60% of A wave

          -  Capillary nonperfusion greater than 50 DA

        Exclusion Criteria:

          -  Subjects who meet any of the following criteria will be excluded from this study:

               -  IOP over 30 mm Hg

               -  Any previous retinal laser photocoagulation to the study eye in treatment naive

               -  Any previous intravitreal injection in study eye (triamcinolone or other) in
                  treatment naive

               -  Any previous vitrectomy in study eye (posterior or anterior associated with
                  vitreous loss in cataract surgery)

               -  Intracapsular cataract extraction (posterior capsule needs to be present)

               -  Previous history of retinal detachment in study eye

               -  Any previous radiation treatments to head/ neck

               -  Inability to assess iris neovascularization (corneal opacity precluding
                  gonioscopy)

               -  Significant cardiovascular disease or cancer that would prevent follow-up visits
                  or completion of the 12 month study

               -  Significant diabetic retinopathy in the fellow eye (diabetic macular edema,
                  proliferative diabetic retinopathy, or high-risk non-proliferative diabetic
                  retinopathy)

               -  Pregnancy (positive pregnancy test)

               -  Participation in another simultaneous medical investigator or trial

               -  Ocular disorders in the study eye that may confound interpretation of study
                  results, including retinal detachment, macular hole, or choroidal
                  neovascularization of any cause (e.g., DME AMD, ocular histoplasmosis, or
                  pathologic myopia)

               -  Concurrent disease in the study eye that could compromise visual acuity or
                  require medical or surgical intervention during the study period

               -  Aphakia or absence of the posterior capsule in the study eye

               -  Previous violation of the posterior capsule is also excluded unless it occurred
                  as a result of YAG laser posterior capsulotomy in association with prior,
                  posterior chamber intraocular lens implantation

               -  History of idiopathic or autoimmune uveitis in either eye

               -  Structural damage to the center of the macula in the study eye preexisting to
                  CRVO likely to preclude improvement in visual acuity following the resolution of
                  macular edema, including atrophy of the retinal pigment epithelium, subretinal
                  fibrosis, laser scar(s)

               -  Vitreomacular traction or epiretinal membrane in the study eye evident
                  biomicroscopically or by OCT

               -  Ocular inflammation (including trace or above) in the study eye

               -  Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye)
                  or current treatment for serious systemic infection

               -  Spherical equivalent of the refractive error in the study eye of more than -8
                  diopters myopia (For patients who have had refractive or cataract surgery in the
                  study eye, pre-operative spherical equivalent refractive error of more than -8
                  diopters myopia is not allowed)

        Systemic Conditions

          -  Uncontrolled Blood pressure exceeding diastolic pressure of 100 mm Hg (sitting) during
             the screening period

          -  Uncontrolled diabetes mellitus

          -  Renal failure requiring dialysis or renal transplant

          -  Pregnancy (positive pregnancy test) or lactation

          -  Premenopausal women not using adequate contraception. The following are considered
             effective means of contraception: surgical sterilization or use of oral
             contraceptives, barrier contraception with either a condom or diaphragm in conjunction
             with spermicidal gel, an IUD, or contraceptive hormone implant or patch.

          -  Any other condition that the investigator believes would pose a significant hazard to
             the subject if the investigational therapy were initiated

          -  Participation in another simultaneous medical investigation or trial

          -  History of other disease, metabolic dysfunction, physical examination finding, or
             other findings giving reasonable suspicion of a disease or condition that
             contraindicates the use an investigational drug, might affect interpretation of the
             results of the study, or render the subject at high risk from treatment complications

        Other

          -  History of allergy to fluorescein, not amenable to treatment

          -  Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality
             to be analyzed and graded by the central reading center

          -  Inability to comply with study or follow up procedures

          -  History of allergy to humanized antibodies or any component of the ranibizumab
             formulation