Efficacy and Safety of Two Treatment Regimens of 0.5 mg Ranibizumab Intravitreal Injections Guided by Functional and/or Anatomical Criteria, in Patients With Neovascular Age-related Macular Degeneration

Study Overview
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Brief Summary
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This study will evaluate and compare two individualized ranibizumab treatment regimens in patients with neovascular (wet) AMD aiming to achieve and to maintain a maximum visual function benefit, while aiming to avoid unnecessary intravitreal injections. The results will be used to generate further recommendations on functional and anatomical monitoring of the disease and timing of treatment administration for patients with neovascular AMD. In this context, the study will investigate the utility of optical coherence tomography (OCT) to aid retreatment decisions with ranibizumab.

Detailed Description
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During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.

Official Title
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A 24-month, Phase IIIb, Randomized, Double-masked, Multicenter Study Assessing the Efficacy and Safety of Two Treatment Regimens of 0.5 mg Ranibizumab Intravitreal Injections Guided by Functional and/or Anatomical Criteria, in Patients With Neovascular Age-related Macular Degeneration

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Visual impairment predominantly due to neovascular age-related macular degeneration AMD Active, newly diagnosed, untreated CNV due to AMD CNV involving the center of the retina A qualifying vision score at study entry Exclusion Criteria: Stroke or myocardial infarction less than 3 Months prior to study entry Active injection or inflammation of either eye at the time of study entry

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RBZ 0.5 mg: VA only (Group I)<br>RBZ 0.5 mg: Visual Acuity (VA) only (Group I) 0.5 mg intravitreal injections of ranibizumab with retreatment based on best-corrected visual acuity (BCVA) loss due to neovascular (wet) age-related macular degeneration (nAMD) | Drug: Ranibizumab<br>* Intravitreal injections of 0.5 mg Ranibizumab<br>|
| Experimental: RBZ 0.5 mg: VA and/or OCT (Group II)<br>RBZ 0.5 mg: VA and/or OCT (Group II) 0.5 mg intravitreal injections of ranibizumab with retreatment based on best-corrected visual acuity (BCVA)loss due to neovascular (wet) age-related macular degeneration (nAMD) and/or signs of wet AMD disease activity on optical coherence tomography (OCT). | Drug: Ranibizumab<br>* Intravitreal injections of 0.5 mg Ranibizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Best-corrected Visual Acuity (BCVA) (Letters) Change up to Month 12 | Visual acuity (VA) was assessed during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the Visual Acuity averaged up to Month 12 Level of VA (Letters) of the Study Eye. | up to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Acuity (Letters) of the Study Eye up to Month 12 | Visual acuity (VA) was assessed using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the Visual Acuity averaged from Baseline to Month 12 Level of VA (Letters) of the Study Eye. | up to Month 12 | 
| Gain of Equal or More Than 1, 5, 10, or 15 Letters in Visual Acuity of the Study Eye From Baseline, at Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Loss of Less Than 5, 10, and 15 Letters in Visual Acuity in the Study Eye From Baseline, at Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Visual Acuity of 73 Letters or More in the Study Eye at Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Month 12 and 24 | 
| Average Visual Acuity Change From Month 3 to Month 4 Through Month 24 in the Study Eye | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Month 3 to Month 24 | 
| Average Visual Acuity Change From Baseline to Month 1 Through Month 12 and 24 in the Study Eye | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Change From Baseline in Central Sub-Field Thickness (CSFT) and Central Sub-Field Volume (CSFV) of the Study Eye Over Time | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Dry Retina in the Study Eye on OCT at Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Month 12 and 24 | 
| Change From Baseline in Lesion Size and Morphology Based on Fluorescein Angiography at Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Treatment Patterns Over Time in Both Treatment Arms | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Change From Baseline in the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) Scores Over Time | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Baseline to Month 12 and 24 | 
| Frequency and Severity of Ocular and Non-ocular Adverse Events Over Time | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. | Screening to Month 12 and 24 |