Regorafenib Eye Drops: Investigation of Efficacy and Safety in Neovascular Age Related Macular Degeneration
Condition: Macular Degeneration
MeSH terms: Macular Degeneration; Wet Macular Degeneration
Intervention: Regorafenib, ophthalmic oily suspension (BAY73-4506); Sham IVT; Ranibizumab; Placebo
Intervention description: Subjects receive Regorafenib as eye drops; Sham injections; Subjects receive Ranibizumab as intravitreal injection; Placebo eye drops
Intervention MeSH terms: Ranibizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 52.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: neovascular Age-related Macular Degeneration

Summary:

      Part A (Phase IIa):

      Primary objectives:

      The study part A is designed to investigate whether the use of regorafenib eye drops can help
      patients with neovascular (wet) Age-Related Macular Degeneration (wAMD) to see better after 4
      weeks and 12 weeks after inclusion into this study.

      Secondary objectives:

      The study will also evaluate the safety and tolerability of the regorafenib eye drops.

      Part B (Phase IIb):

      Primary objectives:

      The study part B is designed to investigate:

        -  how often the regorafenib eye drops need to be given per day

        -  whether the use of regorafenib eye drops can help patients with neovascular (wet)
           Age-Related Macular Degeneration (wAMD) to see better after 4 weeks and 12 weeks after
           inclusion into this study.

      Secondary objectives:

      The study will also evaluate how the different dosings of regorafenib eye drops affect
      patients vision, the safety and the tolerability.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to read (or, if unable to read due to visual impairment, be read to verbatim by
             the person administering the informed consent or a family member) and able to
             understand the informed consent form (ICF)

          -  Men and women ≥ 50 years of age

          -  Active primary subfoveal CNV (Choroidal neovascularization) lesions secondary to AMD
             (Age-related macular degeneration), including juxtafoveal lesions that affect the
             fovea as evidenced by FA (Fluorescein angiography) in the study eye and reviewed by
             the central reading center

          -  The area of CNV must occupy at least 50% of total lesion in the study eye, as
             determined by FA review at the central reading center

          -  Evidence of intraretinal and/or subretinal fluid on OCT (Optical coherence tomography)

          -  Early Treatment Diabetic Retinopathy Study BCVA of 73 to 25 letters (20/40 to 20/320
             Snellen equivalent) in the study eye

          -  Willing, committed, and able to return for all clinic visits and complete all study
             related procedures

          -  Women of childbearing potential and men must agree to use adequate contraception when
             sexually active. This applies since signing of the ICF until one month after the EOS
             (end of study) visit. The definition of adequate contraception will be based on the
             judgment of the investigator.

        Exclusion Criteria:

          -  Concurrent disease in the study eye, other than AMD (e.g., corneal diseases and
             dystrophies, conjunctival diseases, eye lid abnormalities, or any other diseases of
             the cornea and macula, or optic nerve abnormality) that could compromise visual
             acuity, likely require medical or surgical intervention during the study period, would
             limit the potential to gain or lose vision during study treatment, or could otherwise
             confound interpretation of the results

          -  Total lesion size (including neovascularization, scar, blood) > 12 disc areas (30.5
             mm2) as assessed by FA

          -  Only one functional eye, even if that eye is otherwise eligible for the study

          -  Prior ocular or systemic treatment or surgery for neovascular AMD in the study eye
             except dietary supplements or vitamins

          -  Prior treatment with any systemic anti-VEGF (Vascular endothelial growth factor) agent

          -  Use of systemic or ocular treatment with an investigational drug within 12 weeks prior
             to start of study treatment

          -  Any other condition that would require frequent chronic co-administration of other
             topical eye medications that would interfere with study drug administration (e.g.
             contact lens)

          -  Symptoms or conditions consistent with contraindications listed in the current local
             label for ranibizumab

          -  Participation in an investigational study within 30 days prior to start of study
             treatment that involved treatment with any drug (excluding vitamins and minerals) or
             device

          -  Lactating women and women of child-bearing potential with either a positive pregnancy
             test result or no pregnancy test at screening are excluded. Postmenopausal women must
             be amenorrheic for at least 12 months in order not to be considered of child bearing
             potential.