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)

Study Overview
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Brief Summary
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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

Official Title
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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 With Involvement of the FoveAL Center (the iDEAL Study)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: iCo-007 350 mcg
* Drug: iCo-007 700 mcg
* Drug: iCo-007 350 mcg and Laser
* Drug: Ranibizumab and iCo-007 350 mcg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>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 | Drug: iCo-007 350 mcg<br>* iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4<br>* Other names: Group 1;|
| Experimental: Group 2<br>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 | Drug: iCo-007 700 mcg<br>* iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4<br>* Other names: Group 2;|
| Experimental: Group 3<br>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 | Drug: iCo-007 350 mcg and Laser<br>* 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<br>* Other names: Group 3;|
| Experimental: Group 4<br>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 | Drug: Ranibizumab and iCo-007 350 mcg<br>* 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<br>* Other names: Group 4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in VA From 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 | Baseline to month 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability | 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; | Baseline to month 8 | 
| Change in VA From 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 | Baseline to month 12 | 
| Change in Retinal Thickness Measured by OCT From Baseline to Month 8 | Group 1 | Baseline to month 8 | 
| Change in Retinal Thickness Measured | measured by OCT | Baseline to month 12 | 
| Duration of iCo-007 Treatment Effect | treatment effect as measured by VA and OCY thickness | Baseline to month 12 | 
| Peak Plasma Concentration (Cmax)of iCo-007 After Multiple Injections | cmax | Baseline to month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Macular Edema (DME)