The Efficacy of Oral Everolimus in Patients With Neovascular Age-related Macular Degeneration

Study Overview
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Brief Summary
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The study will assess the safety and efficacy of Everolimus (RAD001) alone or in combination with Lucentis in patients with neo-vascular age related macular degeneration (AMD)

Official Title
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A Randomized, Double-masked, Parallel Group Study to Assess the Efficacy of Oral Everolimus, Either Alone or Added to Lucentis, in Patients With Neovascular Age-related Macular Degeneration

Conditions
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Choroidal Neo-Vascular Age-onset Macular Degeneration, Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Everolimus
* Drug: Ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with neovascular Age-Related Macular Degeneration (AMD) Best corrected visual acuity ( BCVA) of 20/40 or worse in study eye Patients with predominantly classic, minimally classic, or occult choroidal neovascularization in the macula of one eye (the study eye) who have had an inadequate response to VEGF inhibitors in the study eye. Inadequate response is defined as a gain of less than one line of visual acuity and persistent macular edema (central sub-fiel thickness ≥ 300 μm as measured by Optical Coherence Tomography (OCT) despite a minimum of 3 treatments with Lucentis or Avastin Exclusion Criteria: Any concurrent ocular condition in the study eye that may result in substantial change in vision during the study Uncontrolled medical conditions such as cancer, angina, diabetes, viral or fungal infections, impaired lung function, history of stroke Patients who have macular edema in the study eye that, in the judgment of the investigator, is unlikely to respond to treatment. Examples of features that may guide the investigator's judgment about unresponsiveness are large regions of geographic atrophy, retinal angiomatous proliferation, or large regions of sub-retinal fibrosis. The presence of one of these features excludes a patient only if the investigator judges the study eye to have irreversible macular edema. active bacterial, fungal or viral infections at the time of enrollment, e.g. hepatitis B or C infection. Patients with risk factors for hepatitis B should be tested for hepatitis B viral load and serological markers at screening (a positive HBV-DNA, HBsAg). Patients with risk factors for hepatitis C should be tested using HCVRNA-PCR at screening. A clinical history of hepatitis B or hepatitis C will exclude the patient from the study. Other protocol-defined inclusion/exclusion criteria may apply

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus 5 mg<br>5 mg orally once daily plus sham ocular injection on Day 1 (Baseline) until Day 28 | Drug: Everolimus<br>* 5 mg oral tablet<br>|
| Active Comparator: Ranibizumab 0.5 mg<br>Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on Day 1 (baseline) | Drug: Ranibizumab<br>* 0.5 mg administered by intravitreal injection<br>|
| Active Comparator: Oral Everolimus (5mg) and Ranibizumab (0.5mg)<br>Everolimus orally 5 mg once daily plus Ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline) | Drug: Everolimus<br>* 5 mg oral tablet<br>Drug: Ranibizumab<br>* 0.5 mg administered by intravitreal injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Central retinal thickness was assessed by Optical coherence tomography (OCT). The primary thickness endpoint was the mean thickness of the foveal field of the macula map produced by the analysis of the sequence of six radial scans. Foveal field thickness was the average thickness of a circular field with a diameter of 1 mm. OCT images were analyzed by a central reading center. | Baseline and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Best corrected visual acuity (BCVA) was assessed on both eyes. BCVA measurements were taken in sitting position using Early Treatment Diabetic Retinopathy Study (ETDRs)-like visual acuity testing charts at an initial testing distance specific to test charts. BCVA is measured from the number of letters the patient can read on the eye chart. | Baseline and week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, macular degeneration, Everolimus, Lucentis, Ranibizumab, Choroidal Neo-Vascular (CNV) age-onset macular degeneration, Age-related Macular Degeneration (AMD)