An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases.

Study Overview
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Brief Summary
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The pupose of this study is to evaluate the safety and the efficacy of ranibizumab in rare VEGF driven ocular diseases.

Official Title
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An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases.

Conditions
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Choroidal Neovascularization, Macular Edema, Glaucoma, Neovascular, Diabetic Retinopathy

Intervention / Treatment
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* Drug: ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active choroidal neovascularization (CNV) Active macular edema (ME) Rubeosis iridis/neovascular glaucoma. Proliferative diabetic retinopathy requiring vitrectomy. Exclusion Criteria: wet Age-related macular degeneration pathologic myopia pseudoxanthoma elasticum diabetic macular edema retinal vein occlusion < 18 years of age History of hypersensitivity to ranibizumab Use of any systemic anti-angiogenic drugs 3 months before inclusion Women of child-bearing potential and Pregnant or nursing (lactating) women. Active or suspected ocular infection

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ranibizumab<br>0.5 mg ranibizumab applied in an individualized regimen as IVT injection of 0.05 mL. | Drug: ranibizumab<br>* One injection of Ranibizumab 0.5 mg and retreatment according to disease activity and/or visual impairment on an as needed regimen (PRN)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) for ocular and non-ocular events. Due to early termination, only descriptive analysis was conducted. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Best Corrected Visual Acuity (BCVA) for Patients With Choroidal Neovascularization (CNV) and Macular Edema (ME) | BCVA change for diseases affecting the macular area either through CNV or ME. BCVA is tested using the ETDRS (Early Treatment Diabetic Retinopathy Study), the Snellen or Monoyer scales. The three scales are designed to measure visual acuity. ETDRS score is expressed in letter, Snellen and Monoyer score in fraction. BCVA assessment is presented in ETDRS after conversion if collected in Snellen or Monoyer. (Monoyer converted to Snellen = 2 x (Monoyer fraction) and Snellen converted to approximate ETDRS letters = 1x log(Snellen fraction). ETDRS letter score was transformed in logMAR unit for statistical analysis (- LogMAR = -(ETDRS-85)/50). The worse ETDRS letter score is 0 (logMAR 2.3) and the best ETDRS letter score is 100 (logMAR -0.3). | 3 months, 12 months | 
| Average Change of Neovascularization Extension for Patients With Neovascular Glaucoma | The extent of iris neovascularization was assessed by iris photography and graded using the Teich and Walsh grading system. This grading system measures the number of quadrant at iris pupillary zone or iris ciliary zone where iris neovascularization (NV) is observed. Grade 0 = No iris vascularization, Grade 1= Less than 2 quadrants of NV at iris pupillary zone, Grade 2 = More than 2 quadrants of NV at iris pupillary zone, Grade 3 =Grade 2 + less than 3 quadrants of NV at iris ciliary zone and/or ectropion uveae; Grade 4 =More than 3 quadrants of NV at iris ciliary zone and/or ectropion uveae) | 3 month, 12 month | 
| Proportion of Patient With Vitreous Cavity Hemorrhage Occurrence for Patient With Proliferative Retinopathy | Occurrence of postoperative vitreous cavity hemorrhage | 3 months, 12 month | 
| Mean Change From Baseline in Change in Central Retinal Thickness for Patients With CNV (Choroidal Neovascularization) and ME (Macular Edema) | CRT in micrometers assessed by Optical Tomography (OCT) at each single study visit. A reduction is thickness indicates an improvement is the lesion area | 3 months, 12 month | 
| Proportion of Patients With Angiographic Leakage | Angiography was taken via fluorescein angiography. Any increases of angiographic leakage was counted between baseline and month 3. Also any decreases of angiographic leakage was counted between baseline and 3 month. | 3 months, 12 month | 
| Ranibizumab Injection | Number of ranibizumab injections needed by decreased visual acuity and/or increasing retinal thickness in 3 months of observation period | 3 months, 12 month |