A Study Evaluating Dosing Regimens for Treatment With Intravitreal Ranibizumab Injections in Subjects With Macular Edema Following Retinal Vein Occlusion
Condition: Macular Edema
MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema
Intervention: Ranibizumab
Intervention description: Liquid ranibizumab (10 mg/ml) was supplied in a sterile solution in single-use vials.
Intervention MeSH terms: Ranibizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This was a Phase IV multicenter, randomized, open-label study, with masking of the vision
      examiner, of the efficacy and safety of intravitreal ranibizumab 0.5 mg in subjects with
      macular edema following Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein
      Occlusion (CRVO).
    

Eligibility criteria:

        Inclusion Criteria:

          -  For sexually active women of childbearing potential, use of an appropriate form of
             contraception (or abstinence) for the duration of the study.

        Ocular Inclusion Criteria (Study Eye)

          -  Foveal center-involved macular edema secondary to branch retinal vein occlusion (BRVO)
             (including hemi-retinal retinal vein occlusion [HRVO]) or central retinal vein
             occlusion (CRVO).

          -  Best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study
             (ETDRS) charts of 20/40 to 20/320 (Snellen equivalent) in the study eye.

          -  Mean central subfield thickness > 300 µm on 2 spectral-domain optical coherence
             tomography measurements (screening and Day 0 [first day of treatment]).

        Exclusion Criteria:

          -  History of cerebral vascular accident or myocardial infarction within 3 months prior
             to Day 0.

          -  History of any systemic anti-vascular endothelial growth factor (VEGF) or pro-VEGF
             treatment within 6 months prior to Day 0.

          -  History of allergy to fluorescein.

          -  History of allergy to ranibizumab injection or related molecule.

          -  Relevant systemic disease that may be associated with increased systemic VEGF levels.
             History of successfully treated malignancies is not an exclusion criterion.

          -  Uncontrolled blood pressure.

          -  Pregnancy or lactation.

          -  Daily use of oral corticosteroids to treat a chronic condition.

          -  Required treatment with injectable corticosteroids to treat a musculoskeletal
             condition.

          -  Participation in an investigational trial within 30 days prior to Day 0 that involved
             treatment with any drug or device that has not received regulatory approval at the
             time of study entry.

        Ocular Exclusion Criteria (Study Eye)

          -  Prior episode of retinal vein occlusion (RVO).

          -  Brisk afferent pupillary defect.

          -  History of any previous intravitreal anti-VEGF therapy for RVO in the study eye.

          -  History of previous therapeutic treatment for RVO, other than anti-VEGF therapy,
             within 4 months prior to the screening visit, including any intraocular
             corticosteroids.

          -  History of previous surgical treatment for RVO, including radial optic neurotomy or
             sheathotomy.

          -  History or presence of age-related macular degeneration (AMD) (dry form graded as
             Age-Related Eye Disease Study [AREDS] Stage 2 or higher or wet form).

          -  History of laser photocoagulation for macular edema within 4 months prior to Day 0.

          -  History of panretinal scatter photocoagulation or sector laser photocoagulation within
             4 months prior to Day 0 or anticipated within the next 4 months following Day 0.

          -  History of pars plana vitrectomy.

          -  History of intraocular surgery within 2 months prior to Day 0 or anticipated within
             the next 7 months following Day 0.

          -  History of yttrium-aluminum-garnet (YAG) capsulotomy performed within 2 months prior
             to Day 0.

          -  Previous filtration surgery in the study eye.

          -  History of herpetic ocular infection.

          -  History of ocular toxoplasmosis.

          -  History of rhegmatogenous retinal detachment.

          -  History of idiopathic central serous chorioretinopathy.

          -  Evidence upon examination of vitreoretinal interface disease either on clinical
             examination or spectral-domain optical coherence tomography (SD-OCT), thought to be
             contributing to macular edema.

          -  Presence of an ocular condition that, in the opinion of the investigator, might affect
             macular edema or alter visual acuity during the study.

          -  Visually significant hemorrhage obscuring the fovea and felt to be a major contributor
             to reduced visual acuity. The subject should be followed and when the hemorrhage in
             the fovea clears to the point that it is no longer a major contributor to reduced
             visual acuity, the subject may be screened for the study.

          -  Presence of a substantial cataract that, in the opinion of the investigator, is likely
             to be decreasing visual acuity by 3 lines or more.

          -  Intra-ocular pressure (IOP) ≥ 30 mmHg. If a subject's IOP is ≥ 30 mmHg, that subject
             will be referred for glaucoma treatment and may be re-screened after 1 month.

          -  Evidence upon examination of pseudoexfoliation.

          -  Aphakia.

          -  Evidence upon examination of external ocular infection, including conjunctivitis,
             chalazion, or significant blepharitis.

          -  Evidence upon examination of any diabetic retinopathy, defined as eyes of diabetic
             patients with more than one microaneurysm outside the area of the vein occlusion
             (inclusive of both eyes).

          -  Other relevant ocular disease that may be associated with increased intraocular VEGF
             levels.

          -  Improvement of ≥ 10 letters on best-corrected visual acuity ETDRS score between
             screening and Day 0.