Efficacy and Safety of Three Different Aflibercept Regimens in Subjects With Diabetic Macular Edema (DME)
Condition: Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Intervention MeSH terms: Aflibercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 463.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Diabetic macular edema; DME

Summary:

      To evaluate the efficacy of long-term treatment with 2 mg aflibercept via different
      intravitreal (IVT) treatment regimens to participants with DME pretreated with 2 mg
      aflibercept every 8 weeks after 5 initial monthly injections for approximately 1 year or more
      (according to the EU label for the first year of treatment)
    

Eligibility criteria:

        Inclusion Criteria:

        The subject's history of aflibercept treatment met all of the following:

          -  Treatment in the study eye was initiated with five monthly (-1 week /+2 weeks) doses
             of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed and
             documented.

          -  Following the above initiation phase, the intervals between treatments were between 6
             weeks and 12 weeks (one exception was allowed).

          -  The interval between the last 2 pre-study injections was ≥ 8 weeks, and visual and
             anatomic outcomes had been stable over this interval.

          -  The subject received the last intravitreal (IVT) injection of aflibercept in the study
             eye 8 weeks (±10 days) before the first planned treatment /randomization in this
             study.

          -  Total prior treatment duration with aflibercept (i.e. from first aflibercept treatment
             ever to enrollment into this study) was 1 year or longer.

        To be met at initiation of pre-study aflibercept treatment:

          -  Type 1 or 2 diabetes mellitus (DM)

          -  Diagnosis of diabetic macular edema (DME) secondary to DM involving the center of the
             macula (defined as the area of the center subfield on optical coherence tomography
             [OCT]) in the study eye

          -  Decrease in vision determined to be primarily the result of DME in the study eye

          -  Best corrected visual acuity (BCVA) in the study eye of Early Treatment Diabetic
             Retinopathy Study (ETDRS) letter score 73 to 24

        Exclusion Criteria:

        At initiation of pre-study aflibercept treatment:

        - Previous treatment with anti-angiogenic drugs in study eye (e.g., pegaptanib sodium,
        bevacizumab, ranibizumab, or aflibercept) within the last 12 weeks before initiation of
        aflibercept pre-study treatment

        At initiation of pre-study aflibercept treatment, screening for this study, and baseline
        for this study:

          -  Prior treatment of the study eye with long acting steroids, either periocular or
             intraocular, in the preceding 120 days or Iluvien intravitreal implant at any time

          -  Active proliferative diabetic retinopathy, current iris neovascularization, vitreous
             hemorrhage, or tractional retinal detachment in the study eye

          -  Cataract surgery or any other intraocular surgery within 90 days of aflibercept
             treatment in the study eye

          -  Ocular inflammation (including trace or above) or history of uveitis in the study eye

          -  Structural damage to the center of the macula in the study eye that was likely to
             preclude improvement in BCVA following the resolution of macular edema including
             atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant
             macular ischemia or organized hard exudates

          -  Concurrent disease in the study eye, other than DME, that could compromise visual
             acuity, require medical or surgical intervention during the study period, or could
             confound interpretation of the results (including advanced glaucoma, retinal vascular
             occlusion, retinal detachment, macular hole, or choroidal neovascularization of any
             cause)

          -  Uncontrolled DM as defined by hemoglobin (Hb) A1c > 12.0% at screening and baseline
             for this study

          -  Any ocular or periocular infection in the preceding 4 weeks in either eye

          -  History of either cerebral vascular accident and/or myocardial infarction within 180
             days before aflibercept treatment