Study Comparing 0.5mg of Ranibizumab and Higher Doses in the Treatment of Clinically Significant Diabetic Macular Edema

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of Ranibizumab in patients with Clinically Significant Diabetic Macular Edema (CSDME). It will also compare treatment outcomes for patients receiving 0.5mg Ranibizumab and higher doses of 1.0mg and 2.0mg Ranibizumab.

Official Title
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A Phase I/II Study Comparing the Treatment of Clinically Significant Diabetic Macular Edema (CSDME) With 0.5mg Ranibizumab, 1.0mg Ranibizumab and 2.0mg Ranibizumab

Conditions
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Clinically Significant Diabetic Macular Edema

Intervention / Treatment
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* Drug: ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type I or Type II diabetic subjects Vision between 20/20 and 20/400 Presence of Clinically Significant Diabetic Macular Edema Exclusion Criteria: Presence of any condition that would prevent clear visualization of the back of the eye Uncontrolled glaucoma Complications of glaucoma Inflammation inside the eye Certain prior eye surgeries, other than cataract surgery Other eye diseases that may compromise the vision in the study eye Certain prior eye treatments Pregnancy Uncontrolled health conditions History of heart attack History of stroke Current participation in another investigational trial

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.5mg transitioning to 2.0mg<br>Ranibizumab-intravitreal injection | Drug: ranibizumab<br>* 0.5mg or 1.0mg intravitreal injection given monthly for 3 months then every other month if needed, for the first year.Patients may be treated monthly as needed. Patients in Cohort 1(the first 30 patients)will be eligible to receive treatment as needed with 2.0mg ranibizumab starting at month 24. Patients in Cohort 2(the remaining 20)will be eligible to receive treatment as needed with 2.0mg ranibizumab starting at month 12.Patients may receive 2.0mg ranibizumab for a period limited to 24 months following administration of the first 2.0mg dose. Patients completing 36 months will be eligible to be followed for an additional 24 months. Starting at Month 36, patients will be able to receive monthly, the assigned dose that they received/or could have received(if re-treatment criteria was met)at Month 35. 2/1/12 - the 2.0mg dose has been discontinued, all subjects will transition to the 0.5mg dose.<br>|
| Active Comparator: 1.0 mg transitioning to 2.0mg<br>Ranibizumab-intravitreal injection | Drug: ranibizumab<br>* 0.5mg or 1.0mg intravitreal injection given monthly for 3 months then every other month if needed, for the first year.Patients may be treated monthly as needed. Patients in Cohort 1(the first 30 patients)will be eligible to receive treatment as needed with 2.0mg ranibizumab starting at month 24. Patients in Cohort 2(the remaining 20)will be eligible to receive treatment as needed with 2.0mg ranibizumab starting at month 12.Patients may receive 2.0mg ranibizumab for a period limited to 24 months following administration of the first 2.0mg dose. Patients completing 36 months will be eligible to be followed for an additional 24 months. Starting at Month 36, patients will be able to receive monthly, the assigned dose that they received/or could have received(if re-treatment criteria was met)at Month 35. 2/1/12 - the 2.0mg dose has been discontinued, all subjects will transition to the 0.5mg dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability of ranibizumab in patients with clinically significant diabetic macular edema |  | month 12 | 
| To compare the treatment of clinically significant diabetic macular edema with 0.5 mg of ranibizumab to 1.0 mg ranibizumab |  | month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in visual acuity as measured by ETDRS from baseline to month 12, 24 36,48 and 60 in each arm. |  | month 12, 24, 36, 48 and 60 | 
| Mean change in central retinal thickness on OCT from baseline to month 12, 24, 36, 48 and 60 in each arm |  | month 12, 24, 36,48 and 60 | 
| Changes observed on the fluorescein angiogram in each arm |  | Month 60 | 
| Mean number of ranibizumab injections required in each arm |  | Month 60 | 
| The need for rescue therapy with laser in each arm |  | Month 60 | 
| Evaluate the efficacy and safety of ranibizumab in the fellow eye in the sub-group of patients who require treatment for clinically significant diabetic macular edema in the fellow eye |  | Month 60 |