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

Phase 2

Terminated

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

Brief Summary: 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)

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Everolimus 5 mg	Everolimus	5 mg orally once daily plus sham ocular injection on Day 1 (Baseline) until Day 28
Ranibizumab 0.5 mg	Ranibizumab	Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on Day 1 (baseline)
Oral Everolimus (5mg) and Ranibizumab (0.5mg)	Everolimus	Everolimus orally 5 mg once daily plus Ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)
Oral Everolimus (5mg) and Ranibizumab (0.5mg)	Ranibizumab	Everolimus orally 5 mg once daily plus Ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)

Primary Outcome Measures

Name	Time	Method
Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT)	Baseline and 4 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus	Baseline and week 4	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.

Locations (7): Novartis Investigative Site
🇬🇧
Southampton, United Kingdom
Retina-Vitreous Associates Medical Group
🇺🇸
Beverley Hills, California, United States
Discover Vision Center
🇺🇸
Independence, Missouri, United States
Novartis Investigative site
🇬🇧
Portsmouth, United Kingdom
Novartis Investigator Site
🇬🇧
Wolverhampton, United Kingdom
Porter Adventist Hospital, Diagnostic Eye Laboratory
🇺🇸
Denver, Colorado, United States
Retinal Consultants Medical Group, Inc.
🇺🇸
Sacramento, California, United States