To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy and safety of 0.5 mg Ranibizumab intravitreal injections in adult patients with visual impairment due to macular edema (ME).

Official Title
-----------------
A 12-month, Randomized, Double-masked, Sham-controlled, Multicenter Study to Evaluate the Efficacy and Safety of 0.5mg Ranibizumab Intravtitreal Injections in Patients With Visual Impairment Due to Vascular Endothelial Growth Factor (VEGF)Driven Macular Edema

Conditions
-----------------
Macular Edema (ME)

Intervention / Treatment
-----------------
* Other: Sham control
* Drug: Ranibizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of active ME secondary to any causes (for adult patients: except diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO)); BCVA must be between ≥ 24 and ≤ 83 letters; Visual loss should be mainly due to the presence of any eligible types of ME. Exclusion Criteria: Women of child-bearing potential, Active malignancies; History of stroke less than 6 months prior to screening; Uncontrolled systemic inflammation or infection, related directly to the underlying causal disease of ME; Active diabetic retinopathy, active ocular/periocular infectious disease or active severe intra-ocular inflammation; Any type of advanced, severe or unstable ocular disease or its reatment; ME with a high likelihood of spontaneous resolution. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab<br>A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity. | Drug: Ranibizumab<br>* Ranibizumab 0.5mg/0.5mL was administered intravitreally to the participant.<br>|
| Sham Comparator: Sham control<br>Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At month 1, if treatment was needed, sham was administered. At month 2, participants switched to open-label ranibizumab on an as needed basis. | Other: Sham control<br>* The sham vial did not contain active drug (empty sterile vial). The sham injection was an imitation of an intravitreal injection using an injection syringe without a needle touching the eye.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best-corrected Visual Acuity (BCVA) in Study Eye | BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement. | Baseline, Month 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in BCVA in Study Eye up to Month 2 | BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement. | Baseline, Month 1, Month 2 | 
| Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye | CSFT wasassessed by optical coherence tomography (OCT). A negative change from baseline indicates improvement. | Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | 
| Change From Baseline in Central Subfield Volume (CSFV) in Study Eye | CSFV was assessed OCT. A negative change from baseline indicates improvement. | Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | 
| Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline | The presence of intra-retinal fluid was assessed by OCT. | Month 2, Month 6, Month 12 | 
| Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline | The presence of subretinal fluid was assessed by OCT. | Month 2, Month 6, Month 12 | 
| Number of Participants With Presence of Active Macular Edema (ME) Leakage | The presence of active ME leakage was assessed by fluorescein angiography (FA). | Month 2 | 
| Number of Participants Requiring Rescue Treatment at Month 1 | Rescue treatment with laser photocoagulation or periocular treatment could be administered at Month 1 only if the participant had a visual acuity loss of > 5 letters due to disease activity from baseline to Month 1. | Month 1 | 
| Average Change From Baseline in BCVA | BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement. | Baseline (BL), month 1 through month 6, month 1 through month 12 | 
| Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters | VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using ETDRS-like visual acuity testing charts at a testing distance of 4 meters. | Month 2, Month 6 , Month 12 | 
| Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss | VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using ETDRS-like visual acuity testing charts at a testing distance of 4 meters. | Month 2, Month 6, Month 12 | 
| Number of Participants With Ranibizumab Treatments | The number of participants administered study treatments, according to treatment frequency, was assessed. | Month 12 | 
| Number of Participants With Re-treatments | The number of participants, administered re-treatments according to treatment frequency, was assessed. Re-treatment was defined as an administration of study medication following at least one non-missed visit where treatment was not administered in the study eye. Up to Month 12, the maximum number of retreatments was 5. | Month 6, month 12 | 
| Number of Primary Reasons for Decision to Treat by Investigator | The total number of primary reasons for decisions to treat was assessed. A single participant could have had multiple primary reasons for treatment. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vision Impairment