A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus (RISE)
Condition: Diabetes Mellitus; Macular Edema
MeSH terms: Macular Edema; Diabetes Mellitus; Edema
Intervention: Ranibizumab; Sham injection
Intervention description: Sterile solution for intravitreal injection.
Intervention MeSH terms: Ranibizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 377.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lucentis; DME; Diabetes; Vision loss

Summary:

      This study is a Phase III, double-masked, multicenter, randomized, sham injection-controlled
      study of the efficacy and safety of ranibizumab injection in patients with clinically
      significant macular edema with center involvement (CSME-CI) secondary to diabetes mellitus
      (Type 1 or 2). This study is identical in design to study NCT00473382 (Protocol ID FVF4168g).

      The open-label extension phase of the study was stopped after receiving FDA approval of the
      study drug (ranibizumab) for diabetic macular edema.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willingness to provide written informed consent and, at U.S. sites, Health Insurance
             Portability and Accountability Act (HIPAA) authorization, and in other countries, as
             applicable according to national laws.

          -  Age ≥ 18 years.

          -  Diabetes mellitus (Type 1 or 2) .

          -  Retinal thickening secondary to diabetes mellitus (DME) involving the center of the
             fovea with central macular thickness ≥ 275 µm in the center subfield as assessed on
             optical coherence tomography (OCT).

          -  Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320
             approximate Snellen equivalent using the Early Treatment Diabetic Retinopathy Study
             (ETDRS) protocol at an initial testing distance of 4 meters.

          -  Decrease in vision determined to be primarily the result of DME and not to other
             causes.

          -  For sexually active women of childbearing potential, use of an appropriate form of
             contraception (or abstinence) for the duration of the study.

          -  Ability (in the opinion of the investigator) and willingness to return for all
             scheduled visits and assessments.

        Exclusion Criteria:

          -  History of vitreoretinal surgery in the study eye.

          -  Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye
             within 3 months of screening.

          -  Previous use of intraocular corticosteroids in the study eye (eg, triamcinolone
             acetonide [TA]) within 3 months of screening.

          -  Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium,
             anecortave acetate, bevacizumab, ranibizumab, etc) within 3 months of the Day 0 (first
             day of treatment) visit.

          -  Proliferative diabetic retinopathy (PDR) in the study eye, with the exception of
             inactive, regressed PDR.

          -  Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or
             preretinal fibrosis involving the macula in the study eye.

        Concurrent Ocular Conditions

          -  Vitreomacular traction or epiretinal membrane in the study eye.

          -  Ocular inflammation (including trace or above) in the study eye.

          -  History of idiopathic or autoimmune uveitis in either eye.

          -  Structural damage to the center of the macula in the study eye that is likely to
             preclude improvement in VA following the resolution of macular edema, including
             atrophy of the retinal pigment epithelium (RPE), subretinal fibrosis, or organized
             hard-exudate plaque.

          -  Ocular disorders in the study eye that may confound interpretation of study results,
             including retinal vascular occlusion, retinal detachment, macular hole, or choroidal
             neovascularization (CNV) of any cause (eg, age-related macular degeneration (AMD),
             ocular histoplasmosis, or pathologic myopia).

          -  Concurrent disease in the study eye that would compromise visual acuity or require
             medical or surgical intervention during the study period.

          -  Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) laser
             capsulotomy within the past 2 months, or any other intraocular surgery within the 90
             days preceding Day 0.

          -  Aphakia or absence of the posterior capsule in the study eye.

          -  Uncontrolled glaucoma or previous filtration surgery in the study eye.

          -  Spherical equivalent of the refractive error in the study eye of more than -8 diopters
             myopia.

          -  Evidence at examination of infectious blepharitis, keratitis, scleritis, or
             conjunctivitis in either eye or current treatment for serious systemic infection.

          -  Uncontrolled blood pressure.

          -  History of cerebral vascular accident or myocardial infarction within 3 months prior
             to Day 0.

          -  Uncontrolled diabetes mellitus.

          -  Renal failure requiring dialysis or renal transplant.

          -  Participation in an investigational trial within 30 days prior to screening that
             involved treatment with any drug (excluding vitamins and minerals) or device.

          -  History of other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding 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 renders the subject at high risk from treatment
             complications.

          -  Pregnancy or lactation.

          -  History of allergy to fluorescein.

          -  History of allergy to ranibizumab injection or related molecule.