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)

Phase 2

Terminated

Conditions: Diabetic Macular Edema

Interventions: Drug: iCo-007 350 mcg and Laser
Drug: iCo-007 350 mcg
Drug: iCo-007 700 mcg
Drug: Ranibizumab and iCo-007 350 mcg

Registration Number: NCT01565148

Lead Sponsor: Johns Hopkins University

Brief 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 185

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Group 3	iCo-007 350 mcg and Laser	Drug: iCo-007 350 mcg and 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
Group 1	iCo-007 350 mcg	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
Group 2	iCo-007 700 mcg	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
Group 4	Ranibizumab and iCo-007 350 mcg	Drug: Ranibizumab and 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

Primary Outcome Measures

Name	Time	Method
Change in VA From Baseline to Month 8	Baseline to month 8	The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 8

Secondary Outcome Measures

Name	Time	Method
Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability	Baseline to month 8	Safety of repeated iCo-007 intravitreal injections in treatment of subjects with Diabetic Macular Edema (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;
Peak Plasma Concentration (Cmax)of iCo-007 After Multiple Injections	Baseline to month 12	cmax
Change in Retinal Thickness Measured by OCT From Baseline to Month 8	Baseline to month 8	Group 1
Change in Retinal Thickness Measured	Baseline to month 12	measured by OCT
Duration of iCo-007 Treatment Effect	Baseline to month 12	treatment effect as measured by VA and OCY thickness
Change in VA From Baseline to Month 12	Baseline to month 12	The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 12