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)

• Number of participants in a given study arm experiencing the same drug-related serious adverse event as a measure of safety and tolerability [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: Yes ]
  Safety of repeated iCo-007 intravitreal injections in treatment of subjects with DME as monotherapy and in combination with ranibizumab or laser photocoagulation. Serious consideration will be given if 2 or more patients in a particular treatment arm experience the same drug-related serious adverse event;
• Change in VA from baseline to month 12 [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]
• Change in retinal thickness measured by OCT from baseline to month 8 [ Time Frame: Baseline to month 8 ] [ Designated as safety issue: No ]
• Change in retinal thickness measured by OCT from baseline to month 12 [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]
• Duration of iCo-007 treatment effect during the 12 month follow-up period as measured by VA and OCt thickness [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]
• Peak plasma concentration (Cmax)of iCo-007 after multiple injections [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]

• 2 or more patients in a given study arm experiencing the same drug-related SAE [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: Yes ]
  Safety of repeated iCo-007 intravitreal injections in treatment of subjects with DME as monotherapy and in combination with ranibizumab or laser photocoagulation. Serious consideration will be given if 2 or more patients in a particular treatment arm experience the same drug-related serious adverse event;
• Change in VA from baseline to month 12 [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]
• Change in retinal thickness measured by OCT from baseline to month 8 [ Time Frame: Baseline to month 8 ] [ Designated as safety issue: No ]
• Change in retinal thickness measured by OCT from baseline to month 12 [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]
• Duration of iCo-007 treatment effect during the 12 month follow-up period as measured by VA and OCt thickness [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]
• Peak plasma concentration (Cmax)of iCo-007 after multiple injections [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]

• 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 OCT from baseline to month 8 and month 12

• Drug: iCo-007 350 mcg
  iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4
  Other Name: Group 1
• Drug: iCo-007 700 mcg
  iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4
  Other Name: Group 2
• Drug: iCo-007 350 mcg Plus Laser
  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
  Other Name: Group 3
• Drug: Ranibizumab Plus iCo-007 350 mcg
  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
  Other Name: Group 4

• Experimental: Group 1
  Intervention: Drug: iCo-007 350 mcg
• Experimental: Group 2
  Intervention: Drug: iCo-007 700 mcg
• Experimental: Group 3
  Intervention: Drug: iCo-007 350 mcg Plus Laser
• Experimental: Group 4
  Intervention: Drug: Ranibizumab Plus iCo-007 350 mcg

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 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 AST, 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

• Juvenile Diabetes Research Foundation
• iCo Therapeutics Inc.