Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Branch Retinal Vein Occlusion (BRVO)

Study Overview
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Brief Summary
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This clinical trial is designed to compare ranibizumab in comparison with Dexamethasone implant after 6 months of treatment. In the study arm Ranibizumab will be given monthly in a pro re nata scheme whereas the comparator Dexamethasone implant is given once at Month 0 with sham injections PRN afterwards.

Official Title
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A 6-month Multicenter, Randomized, Double-masked Phase IIIb-study Comparing the Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Visual Impairment Due to Macular Edema Following Branch Retinal Vein Occlusion (BRVO)

Conditions
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Visual Impairment, Macular Edema, Branch Retinal Vein Occlusion

Intervention / Treatment
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* Drug: Ranibizumab
* Other: Dexamethasone Implant
* Other: Sham injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with visual impairment due to macular edema following BRVO Diagnosis of BRVO at maximum 6 months prior to Screening BCVA using ETDRS charts of 20/40 to 20/400 in the study eye Exclusion Criteria: Media clarity, pupillary dilation and patient cooperation not sufficient for adequate fundus photographs Central retinal thickness (CRT) < 250 µm in the study eye Prior episode of RVO in the study eye Active formation of new vessels in the study eye Anti-VEGF-treatment in the study or the fellow eye 3 months prior to Baseline IOP ≥ 30mmHg or uncontrolled glaucoma; patients may be re-screened after 1 month if they have undergone glaucoma treatment Improvement of > 10 letters on BCVA between Screening and Baseline Other protocol-defined inclusion/exclusion criteria may apply

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<br>Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally | Drug: Ranibizumab<br>* Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally. Ranibizumab was formulated as a sterile solution aseptically filled in a sterile glass vial. It was suitable for single use only and the content of the vial was not allowed to be split<br>|
| Sham Comparator: Dexamethasone<br>Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months | Other: Dexamethasone Implant<br>* Comparator Ozurdex® (dexamethasone) was formulated as a rod shaped implant to be inserted into the eye by an applicator. The implant as well as the respective applicator were suitable for single use only.<br>Other: Sham injection<br>* Sham injection: Empty sterile syringes were provided so that masking could be maintained. Either empty syringes in the case of sham injections or pre-filled syringes in the case of ranibizumab injections were visible to the patient in the room of study drug administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline | the average of the changes in BCVA (letters) from baseline to any post-baseline visit, i.e. the mean of six differences to baseline for the six post-baseline visits at month 1 to 6 | Baseline, month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean BCVA Change From Baseline to Endpoints Month 1 to Month 6 | The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors | Baseline, month 6 | 
| Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment | BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained 15, 10 or 5 more letters of visual acuity at month 6 as compared with baseline | Baseline, 6 month | 
| Time to Achieve a Significant Improvement ≥ 15 Letters | The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts | Baseline, month 6 | 
| Change Over Time in BCVA | The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors | baseline, month 6 | 
| Change Over Time of the Central Retinal Thickness (CRT) | Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation | Baseline, month 6 | 
| Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires | The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function. | Baseline, month 6 | 
| Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires | SF-36 summary measures are norm-based scores with mean = 50 and SD = 10. Higher scores indicate better health | Baseline, month 6 | 
| Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires | The EQ-5D visual analog scale ranges from 0 to 100, 0 representing the worst and 100 the best imaginable health state. | Baseline, month 6 | 
| Rate of the Internal Ocular Pressure (IOP) | The proportion of patients with ≥ 10% increase in IOP compared to baseline at any post-baseline visit. | Baseline, month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Visual impairment, macular edema, branch retinal vein occlusion, Dexamethasone implant, Ranibizumab