Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2)
Condition: Central Retinal Vein Occlusion
MeSH terms: Retinal Vein Occlusion
Intervention: aflibercept; bevacizumab
Intervention MeSH terms: Bevacizumab; Aflibercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 362.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      SCORE2 is a multicenter, prospective, randomized, phase III clinical trial in which all
      participants enrolled will be followed for up to 2.5 years. SCORE2 is designed as a
      non-inferiority trial, with study eyes randomized to intravitreal bevacizumab (1.25 mg) every
      4 weeks vs. intravitreal aflibercept (2.0 mg) every 4 weeks. SCORE2 aims to determine if
      bevacizumab is non-inferior to aflibercept for the treatment of macular edema associated with
      central retinal vein occlusion (CRVO), with the primary outcome of visual acuity measured at
      Month 6.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have center-involved macular edema secondary to CRVO. Eyes may be
             enrolled as early as the time of diagnosis of the macular edema. The definition of
             CRVO used in SCORE will also be used for the purposes of SCORE2: a CRVO is defined as
             an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein
             occlusion (e.g., telangiectatic capillary bed) and a dilated venous system (or
             previously dilated venous system) in all 4 quadrants.

          -  Due to the similarities of a hemiretinal vein occlusion (HRVO) to CRVO,HRVO will be
             classified as CRVO for the purposes of this clinical trial. Eyes classified as having
             a HRVO will be limited to no more than 25% of the planned sample size. A HRVO is
             defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of
             retinal vein occlusion (e.g. telangiectatic capillary bed) and a dilated venous system
             (or previously dilated venous system) in 5 or more clock hours but less than all 4
             quadrants. Typically, a HRVO is a retinal vein occlusion that involves 2 altitudinal
             quadrants.

          -  E-Early Treatment Diabetic Retinopathy Study (ETDRS)visual acuity score of greater
             than or equal to 19 letters (approximately 20/400) and less than or equal to 73
             letters (approximately 20/40) by the ETDRS visual acuity protocol. The investigator
             must believe that a study eye with visual acuity between 19 and 33 letters is
             perfused.

          -  Retinal thickness on SD-OCT measurement, defined as central subfield thickness of 300
             µm or greater. If the SD-OCT measurement is taken from a Heidelberg Spectralis
             Machine, the central subfield thickness should be 320 µm or greater.

          -  Media clarity, pupillary dilation and participant cooperation sufficient for adequate
             fundus photographs.

        Exclusion Criteria:

          -  A condition that, in the opinion of the investigator, would preclude participation in
             the study (e.g., chronic alcoholism or drug abuse, personality disorder or use of
             major tranquilizers indicating difficulty in long term follow-up, likelihood of
             survival of less than 12 months).

          -  Participation in an investigational trial within 30 days of study entry that involved
             treatment with any drug that has not received regulatory approval at time of study
             entry.

          -  History of allergy to any anti-VEGF agent, corticosteroid, or component of the
             delivery vehicle.

          -  The participant will be moving out of the area of the clinical site to an area not
             covered by another clinical site during the 12 months of the study.

          -  Positive urine pregnancy test: all women of childbearing potential (those who are
             pre-menopausal and not surgically sterilized) may participate only if they have a
             negative urine pregnancy test, and if they do not intend to become pregnant during the
             timeframe of the study. Women who are sexually active with a male partner must agree
             to use at least one of the following birth control methods: hormonal therapy such as
             oral, implantable or injectable chemical contraceptives; mechanical therapy such as
             spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine
             device (IUD); or surgical sterilization of partner.

          -  Women who are breast-feeding.

          -  Examination evidence of vitreoretinal interface disease (e.g., vitreomacular traction,
             epiretinal membrane), either on clinical examination or OCT thought to be contributing
             to macular edema.

          -  An eye that, in the investigator's opinion, would not benefit from resolution of
             macular edema such as eyes with foveal atrophy, dense pigmentary changes or dense
             subfoveal hard exudates.

          -  Presence of an ocular condition that, in the opinion of the investigator, might affect
             macular edema or alter visual acuity during the course of the study (e.g., age-related
             macular degeneration, uveitis or other ocular inflammatory disease, neovascular
             glaucoma, iris neovascularization, Irvine-Gass Syndrome, prior macula-off
             rhegmatogenous retinal detachment).

          -  Presence of a substantial cataract that, in the opinion of the investigator, is likely
             to be decreasing visual acuity by 3 lines or more (i.e., a 20/40 cataract).

          -  History of laser photocoagulation for macular edema within 3 months prior to
             randomization.

          -  History of intravitreal corticosteroid within 4 months of randomization.

          -  Intravitreal anti-VEGF injection within 2 months of randomization. Note: Enrollment
             will be limited to no more than 25% of the planned sample size with any history of
             anti-VEGF treatment. Once this number of eyes has been enrolled, any history of
             anti-VEGF treatment will be an exclusion criterion. For enrollment of study eyes with
             prior intravitreal anti-VEGF agents, in the opinion of the investigator, the treatment
             response to prior anti-VEGF treatment must be either incomplete or the study eye had
             developed recurrent CRVO-associated macular edema, such that the study eye would
             benefit from additional anti-VEGF treatment.

          -  History of peribulbar or retrobulbar corticosteroid use for any reason within 2 months
             prior to randomization.

          -  History of panretinal scatter photocoagulation (PRP) or sector laser photocoagulation
             within 3 months prior to randomization or anticipated within the next 3 months
             following randomization.

          -  History of major ocular surgery (including cataract extraction, scleral buckle, any
             intraocular surgery, etc.) within 4 months prior to randomization or anticipated
             within the next 6 months following randomization.

          -  History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior
             to randomization.

          -  Aphakia.

          -  Presence of an anterior chamber intraocular lens

          -  Examination evidence of external ocular infection, including conjunctivitis, chalazion
             or significant blepharitis.

          -  History of macular detachment.

          -  Examination evidence of any diabetic retinopathy.