Assess the Efficacy/Safety of Intravitreal Ranibizumab in Patients With Vision Loss Due to Choroidal Neovascularization.

Study Overview
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Brief Summary
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This study was conducted to evaluate the efficacy and safety of 0.5 mg ranibizumab in adult and adolescent patients with visual impairment due to choridal neovascularization (CNV).

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

Conditions
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Choroidal Neovascularization (CNV)

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of active CNV secondary to any causes with the CNV or its sequelae affecting the fovea; BCVA must be between ≥ 24 and ≤ 83 letters in the study eye; Visual loss in the study eye should mainly be due to the presence of any eligible types of CNV; Key Exclusion Criteria: Women of child-bearing potential; Active malignancies; History of stroke less than 6 months prior to screening; Uncontrolled systemic inflammation or infection; Active diabetic retinopathy, active ocular/periocular infectious disease or active severe intra-ocular inflammation; CNV- conditions with a high likelihood of spontaneous resolution; History of intravitreal treatment with steroids; History of laser photocoagulation; History of intraocular treatment with any anti-angiogenic drugs.

Ages Eligible for Study
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Minimum Age: 12 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: 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 could switch 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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best-corrected Visual Acuity (BCVA) in Study Eye 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. The data were analyzed using mixed model repeated measures (MMRM) which contained scheduled visit, the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate and treatment group by visit and visit by centered baseline BCVA interactions. 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. The data were analyzed using analysis of covariance (ANCOVA) model which contained the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate. A positive change from baseline indicated improvement. | Baseline, Month 1, Month 2 | 
| Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye | CSFT was assessed 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. | Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | 
| Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline | The presence of intra-retinal fluid was assessed by OCT. | Baseline, Month 2, Month 6, Month 12 | 
| Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline | Presence of subretinal fluid in study eye compared to baseline | Baseline, Month 2, Month 6, Month 12 | 
| Number of Participants With Presence of Active Chorioretinal Leakage | The presence of active chorioretinal leakage was assessed by photography imaging, i.e. fluorescein angiography (FA). | Baseline, Month 2, Month 6, Month 12 | 
| 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. BCVA was assessed at each month from Month 1 through Month 6 or at each month from Month 1 through month 12, and the data were averaged. The outcome measure is reporting the change between baseline and average BCVA from Month 1 through Month 6 or from Month 1 through Month 12 (average BCVA - baseline BCVA). 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 Requirement for 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 | 
| Number of Participants With Ranibizumab Treatments in Study Eye | 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 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. | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vision Impairment, Abnormal growth of blood vessels