Randomized Study for Efficacy and Safety of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in Patients With nAMD

Study Overview
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Brief Summary
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This study was designed to evaluate the efficacy and safety of two different regimens of 0.5 mg ranibizumab given as intravitreal injection in patients with neovascular age-related macular degeneration

Detailed Description
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This was a 12-month, phase IIIb, randomized, Visual Acuity assessor-masked, multi-center, interventional study assessing the efficacy and safety of the TER vs monthly regimens of 0.5 mg ranibizumab intravitreal (IVT) injections in patients with newly diagnosed nAMD. Patients will be randomized 1:1 into one of two treatment arms, Treat and Extend or monthly regimens. There will be 3 periods in this study: Screening period (up to 14days), treatment period (11 months), follow-up period (1 month). At randomization visit patients will be randomized into one of the 2 treatment groups Group I ranibizumab 0.5 mg based on monthly treatment or Group II ranibizumab 0.5 mg based on TER (randomization ratio of 1:1) and will receive the first dose of Investigational treatment. Patients in Group I the following visits will perform on monthly intervals. For patients in Group II the investigator will evaluate disease activity (i.e., signs of exudation) based on SD-OCT, and in case of absence of disease activity every next visit will be 2 weeks), with a maximum of a 12-week interval.

Official Title
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A 12-month, Phase 3b, Randomized, Visual Acuity Assessor-masked, Multicenter Study Assessing the Efficacy and Safety of Ranibizumab 0.5mg in Treat and Extend Regimen Compared to Monthly Regimen, in Patients With Neovascular Age-related Macular Degeneration

Conditions
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Age-related Macular Degeneration, Choroidal Neovascularization

Intervention / Treatment
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* Drug: Ranibizumab 0.5mg
* Drug: Ranibizumab 0.5mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female patients, ≥50 years of age with signed informed consent before study procedures Visual impairment predominantly due to nAMD. Active CNV secondary to AMD confirmed by presence of active leakage from CNV seen by fluorescein angiography (FA) and/or color fundus photography Presence of intra- or subretinal fluid/hemorrhage seen by SD-OCT BCVA score must be ≤ 78 and ≥ 23 letters at 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts (approximate Snellen equivalent of 20/32 and 20/320) Key Exclusion Criteria: Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk. Stroke or myocardial infarction within 3 months prior to Screening. Any active periocular or ocular infection or inflammation in both eyes. Ocular disorders in the study eye at the time of enrollment that may confound interpretation of study results and compromise visual acuity. Presence of amblyopia or amaurosis in the fellow eye. History of treatment with any anti-angiogenic drugs (including any anti- vascular endothelial growth factor (anti-VEGF) agents) e.g., bevacizumab [Avastin®], aflibercept [Eylea®]) or vPDT in the study eye. History of intravitreal treatment with corticosteroids within 6 months and history of intra-ocular surgery within 3 months in the study eye prior to the Screening. Pregnant or nursing (lactating) women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Ages Eligible for Study
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Minimum Age: 50 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I ranibizumab 0.5 mg monthly<br>Ranibizumab 0.5 mg/0.05 mL (Monthly regimen) up to month 11 | Drug: Ranibizumab 0.5mg<br>* 0.5 mg ranibizumab (intravitreal injections) prefilled syringe)<br>* Other names: Lucentis;|
| Active Comparator: Group II ranibizumab 0.5 mg TER<br>Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen up to month 11 | Drug: Ranibizumab 0.5mg<br>* 0.5 mg ranibizumab (intravitreal injections) prefilled syringe)<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement | Baseline to month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Visits Scheduled | The number of visits scheduled according to the treat and extend regimen after treatment initiation | From Month1 to Month 11 | 
| Change in BCVA From Baseline to Month 12 | Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters | Baseline to Month 12 | 
| Average BCVA Change From Baseline to Month 12 | Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from Baseline to Month 12 | Baseline and every month for 12 months | 
| Mean Change in Visual Acuity BCVA (Letters) From Baseline to Month 12 | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like charts while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and compare to Baseline | Baseline and every month for 12 months | 
| Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 | 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 increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 12 as compared with baseline | Baseline and every month for 12 months | 
| Number of Patients With Best Corrected Visual Acuity (BCVA) Loss <5, <10, and <15 Letters by Visit | Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters.Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. | Baseline and every month for 12 months | 
| Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 | Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 12 indicates a positive outcome | Baseline and every month for 12 months | 
| The Mean Number of Treatment Frequency | The number of injections received | Month 12 | 
| The Average Number of Days Between Injections | The average dosing interval was measured as the average number of days between injections | Month 12 | 
| Percentage of Participants With Fluid Free Macula Over Time up to Month 12 | OCT (optical coherence tomography) was used to assess intra-retinal fluid as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography). Fluid free macula refers to absence of macular edema (as assessed by the reading center). The full analysis set was used for this evaluation but the count presented are the counts of patients in the specific treatment group who have a value for the macular edema (center involvement) at study completion. These total counts are used as the denominator for the percentages | Month 12 | 
| Change in Central Subfield Retinal Thickness (CSFT) Over Time | OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center. The Ns in the rows is the number of patients with a value for both baseline and the specific post-baseline visit | Month 12 | 
| Percentage of Patients With Choroidal Neovascularization (CNV) Leakage Assessed by Fluorescein Angiography (FA) in the Study Eye at | To evaluate presence of active CNV leakage on fluorescein angiography (FA) by reading center over time up to Month 12. The full analysis set was used for this evaluation but the count presented are the counts of patients in the specific treatment group who have a value for the presence of leakage at study completion. These total counts are used as the denominator for the percentages. | Month 12 | 
| Change From Baseline in Composite Score of the National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25) | The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicates the best possible response. The composite score and score of each of each construct also ranged from 0 to 100 as they are calculated as total scores divided by the number of questions. The higher the values of total scores represent better outcome | Baseline, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ranibizumab, Lucentis, choroidal neovascularization, age-related macular degeneration, treat and extend regimen