A Randomized, Multi-center, Phase II Study of the Safety, Tolerability and Bioactivity of Repeated Intravitreal Injections of iCo-007 as Monotherapy or in Combination With Ranibizumab or Laser Photocoagulation in the Treatment of Diabetic Macular Edema (the iDEAL Study)
Condition: Diabetic Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: iCo-007 350 mcg; iCo-007 700 mcg; iCo-007 350 mcg and Laser; Ranibizumab and iCo-007 350 mcg
Intervention description: iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4; iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4; iCo-007 (350 μg) as an intravitreal injection at baseline followed 7 days later by laser photocoagulation. At M4, intravitreal injection of iCo-007 (350 μg) will be given as mandatory treatment. If the eye also meets retreatment criteria, it will also receive the second laser photocoagulation; Ranibizumab (0.5 mg) intravitreal injection at baseline followed by iCo-007 (350 μg) intravitreal injection 2 weeks later; re-treatment with ranibizumab (0.5 mg) mandatory at M4 followed by iCo-007 (350 μg) 2 weeks later
Intervention MeSH terms: Ranibizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 185.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Diabetic Macular Edema (DME)

Summary:

      -  To assess the safety of repeated iCo-007 intravitreal injections in treatment of
           subjects with diabetic macular edema as monotherapy and in combination with ranibizumab
           or laser photocoagulation

        -  To assess the change in visual acuity and retinal thickness on optical coherence
           tomography (OCT) from baseline to month 8 and month 12
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years

          -  Have diabetes mellitus type I or II (insulin or non-insulin dependent) with HbA1c
             ≥5.5% and HbA1c ≤13%; have non-proliferative diabetic retinopathy, or inactive
             proliferative diabetic retinopathy, or proliferative diabetic retinopathy with a
             reasonable expectation that panretinal photocoagulation will not be required during
             the study follow-up period

          -  Have diabetic macular edema with central subfield thickness of ≥250 microns (confirmed
             by Stratus Time-Domain(TD) OCT

          -  Have best corrected visual acuity (ETDRS) that is Snellen equivalent of

               -  20/32 and ≥20/320, inclusive

          -  Be willing and able to sign an approved written informed consent. If a patient has a
             central nervous system disorder (i.e. dementia) that will not allow him/her to
             understand the consent independently, the patient will not be allowed to join the
             study

          -  Be able to attend all scheduled study visits

          -  Women who are not lactating or pregnant and are willing to use adequate contraception
             during the study period, if appropriate

        Exclusion Criteria:

          -  Have macular or perimacular edema secondary to an etiology other than diabetes

          -  Have concurrent retinal diseases other than diabetic retinopathy

          -  Have additional ocular diseases compromising visual acuity and/or interfering with
             study assessments; patients who have glaucoma but deemed stable (intraocular pressure
             ≤ 25 mmHg at screening) on medications or status post surgery, may participate in the
             study

          -  Participant has a history of prior pars plana vitrectomy

          -  Subjects with significant cataract or or posterior capsular opacification that may
             need intervention within one year or vitreous opacity that hinder study assessment
             (i.e.fundus examination) which requires intervention within a year

          -  Subjects who have DME with severe capillary non-perfusion (avascular zone diameter
             >1,000 microns)

          -  Have an allergy to fluorescein dye

          -  Have terminal renal disease (on active kidney dialysis), cerebral vascular
             accident(including TIA), myocardial infarction or congestive heart disease within 6
             months of study enrollment, liver damage (2x upper limit of normal range for aspartate
             aminotransferase (AST), Alanine aminotransferase (ALT) or total bilirubin). Patients
             who may have received renal transplant in the past and now have stable renal function,
             may participate in the study

          -  Subjects with systolic blood pressure higher than 180 mm Hg or diastolic above 100 mm
             Hg, with or without anti-hypertensive treatment

          -  Have a history of panretinal photocoagulation (PRP) in the study eye within 3 months
             of study entry or are likely to have PRP in the study eye during study participation

          -  Had macular photocoagulation or ocular surgery within 3 months of study entry in the
             study eye

          -  Received intraocular or periocular injection of steroids in the study eye (e.g.,
             triamcinolone) within 3 months of study entry or anti-angiogenic drugs (pegaptanib
             sodium, ranibizumab, bevacizumab, VEGF-TRAP, protein kinase C inhibitor, etc.) within
             2 months of study entry; history of usage of topical or systemic steroids within 3
             months of study entry is not an exclusion