Efficacy and Safety Study of iSONEP With & Without Lucentis/Avastin/Eylea to Treat Wet AMD
Condition: Exudative Age-related Macular Degeneration
MeSH terms: Macular Degeneration; Choroidal Neovascularization
Intervention: 4.0 mg iSONEP; 0.5 mg iSONEP; 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; sham injection
Intervention description: 4.0 mg iSONEP given monthly intravitreously for 4 months; 0.5 mg iSONEP given monthly intravitreously for 4 months; 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea given monthly intravitreously for 4 months; administered monthly for 4 months
Intervention MeSH terms: Bevacizumab; Ranibizumab; Aflibercept; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 158.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: choroidal neovascularization; age-related macular degeneration; iSONEP; sonepcizumab; Lucentis; ranibizumab; Avastin; bevacizumab; Eylea; aflibercept

Summary:

      The purpose of the study is to determine the safety and efficacy of 4 monthly injections of
      iSONEP given alone or in combination with Lucentis, Avastin or Eylea in subjects with wet
      Age-related Macular Degeneration (AMD). iSONEP not only has an anti-permeability effect, but
      also has anti-angiogenic, anti-inflammatory, and anti-fibrotic properties. The drug may
      therefore have the ability to achieve better visual outcomes than Lucentis, Avastin or Eylea,
      particularly in those subjects who do not demonstrate a robust response to Lucentis, Avastin
      or Eylea after several monthly injections. Further, the combination of Lucentis, Avastin or
      Eylea and iSONEP may be additive or synergistic. By inhibiting the multiple mechanisms that
      contribute to exudative-AMD-related vision loss, better visual outcomes may be possible than
      with Lucentis, Avastin or Eylea alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥50 years of age with a diagnosis of wet AMD

          -  Subjects who have received 3 injections of Lucentis or Avastin or Eylea within 12
             months prior to screening

          -  Active subfoveal CNV secondary to AMD (leakage on FA)

          -  Presence of residual subretinal or intraretinal fluid on Cirrus or Spectralis SDOCT

          -  SDOCT in the 1 mm central macular subfield on the retinal map analysis of ≥250 μm at
             screening

          -  ETDRS BCVA of ≥25 and ≤73 letters (approximately 20/320 and 20/40 on the Snellen
             scale) at screening and on Day 0

          -  In the fellow eye, ETDRS BCVA of 20/400 or better

          -  Subject with serous pigment epithelial detachment (PED) (any part of which may be
             subfoveal) with intraretinal and/or subretinal fluid may be included

        Exclusion Criteria:

          -  Most recent IVT injection of Lucentis or Avastin fewer than 28 days and more than 65
             days prior to screening

          -  Most recent IVT injection of Eylea fewer than 42 days and more than 79 days prior to
             screening

          -  Previous photodynamic therapy (PDT) or Macugen® at any time point

          -  Focal thermal laser or grid laser within 3 months prior to Day 0

          -  Use of IVT, subtenon or subconjunctival steroids within 3 months prior to Day 0

          -  Use of topical ophthalmic corticosteroids 2 weeks prior to Day 0

          -  Intraocular surgery, including cataract surgery, and / or laser of any type within 3
             months prior to Day 0 or anticipated need for ocular surgery or ophthalmic laser
             treatment during the study period

          -  Subjects previously treated with, or are currently receiving treatment with another
             investigational agent or device for neovascular AMD in the study eye

          -  Retinal total lesion size >12 disc areas (30.5 mm2), including blood, scars and
             neovascularization as assessed by FA in the study eye

          -  Presence of a fibrovascular PED extending underneath the center of the fovea

          -  Presence of retinal angiomatous proliferation (RAP) lesions

          -  Presence of polypoidal choroidal vasculopathy (PCV) (if suspected, Indocyanine Green
             Angiography (ICG) should be performed at the discretion of the Investigator)

          -  Subretinal hemorrhage in the study eye if any of the following is true: (i) the
             subretinal hemorrhage represents 50% or more of the total lesion area; (ii) subfoveal
             blood is 1 or more disc areas in size (iii) subfoveal blood where the fovea is
             surrounded by less than 270 degrees of visible CNV on FA

          -  Scar or fibrosis making up >50% of total lesion area in the study eye

          -  Anatomic damage to the center of the fovea including fibrosis, scarring or atrophy

          -  History of a retinal pigment epithelial tear

          -  History of vitreous hemorrhage within 4 weeks prior to screening in the study eye

          -  Clinical evidence of diabetic retinopathy, diabetic macular edema or any other
             vascular disease affecting the retina, other than AMD, in either eye

          -  Uncontrolled glaucoma defined as: (i) as intraocular pressure ≥25 mmHg despite
             treatment with anti glaucoma medication in the study eye or (ii) by the Investigator

          -  Prior trabeculectomy or other filtration surgery in the study eye (prior laser
             trabeculoplasty is allowed)