Safety and Efficacy of Ranibizumab in Diabetic Macular Edema With Center Involvement

Study Overview
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Brief Summary
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This study evaluated the safety and efficacy of ranibizumab on retinal edema and visual acuity in patients with diabetic macular edema with center involvement.

Official Title
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A Randomized, Double-masked, Multi-center, Phase II Study Assessing the Safety and Efficacy of Two Concentrations of Ranibizumab (Intravitreal Injections) Compared With Non-treatment Control for the Treatment of Diabetic Macular Edema With Center Involvement

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Ranibizumab 0.3 mg
* Drug: Ranibizumab 0.5 mg
* Drug: Sham injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetic macular edema with center involvement in at least one eye Type 1 or type 2 diabetes mellitus diagnosed 2 years prior to screening Laser photocoagulation in the study eye can be withheld for at least 3 months after randomization Exclusion Criteria: Patients with uncontrolled systemic or ocular diseases Have any history of any intraocular surgery in the study eye within the past 6 months preceding screening Conditions that require chronic concomitant therapy with systemic or topical ocular corticosteroids Other protocol-defined inclusion/exclusion criteria applied to the study.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab 0.3 mg<br>Participants received monthly intravitreal injections with 0.3 mg ranibizumab (6 mg/ml) for up to 12 months. At each monthly visit from month 1 and onwards, the evaluating physician decided whether an increase in the dose to 0.6 mg was needed according to set criteria. If the dose was increased, all subsequent administrations were of the higher dose unless treatment had been withheld for more than 45 days (for any reason), in which case injections restarted with the initial dose. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. | Drug: Ranibizumab 0.3 mg<br>* 6 mg/ml ranibizumab solution for intravitreal injection<br>|
| Experimental: Ranibizumab 0.5 mg<br>Participants received monthly intravitreal injections with 0.5 mg ranibizumab (10 mg/ml) for up to 12 months. At each monthly visit from month 1 and onwards, the evaluating physician decided whether an increase in the dose to 1.0 mg was needed according to set criteria. If the dose was increased, all subsequent administrations were of the higher dose unless treatment had been withheld for more than 45 days (for any reason), in which case injections restarted with the initial dose. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. | Drug: Ranibizumab 0.5 mg<br>* 10 mg/ml ranibizumab solution for intravitreal injection<br>|
| Sham Comparator: Sham injection<br>Participants in the control group received 12 monthly sham intravitreal injections. The evaluation was performed using the same criteria for dose doubling as in active treatment groups. The injection was a mimicked by an empty syringe without a needle. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. | Drug: Sham injection<br>* Non-treatment control for sham intravitreal injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12 | Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters as described in the Study Operations Manual. | Baseline through the end of study (Month 12) | 
| Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye at Month 12 | Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters as described in the Study Operations Manual. | Baseline through the end of study (Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Central Retinal Thickness (µm) of the Study Eye at Month 12 | Optical Coherence Tomography (OCT) was assessed on both eyes at every study visit. These assessments were performed by trained personnel at the sites. OCT imaging was performed using the Zeiss Humphrey System Model 2000 (or later) with version A6.1 software running under Windows 95 or Windows 98. The analysis of the OCT images were performed by the Photographic Reading Center which provided a study manual and training materials. OCT operators, systems and software were certified prior to any evaluation of study patients. | Baseline through the end of study (Month 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DME, Diabetic macular edema, ranibizumab, Diabetic macular edema with center involvement