Visual impairment due to neovascular AMD MedDRA version: 19.0 Level: LLT Classification code 10060837 Term: Choroidal neovascularization System Organ Class: 100000004853
Conditions
Sponsors
Novartis Pharmaceuticals UK Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for patient 1. Written informed consent must be obtained before any assessment is performed. 2. Age =50 years. 3. BCVA =23 ETDRS letters, at both the Screening Visit and Baseline Visit in the Study eye. 4. Active, angiographically documented CNV lesion in study eye (e.g. leakage on fluorescein angiography plus intraretinal, subretinal or sub-retinal pigment epithelium (RPE) fluid on SD/HD-OCT) secondary to AMD at Screening. 5. Evidence of active CNV involving the center of the fovea in the study eye (e.g. pigment epithelium detachment, subretinal or sub-RPE hemorrhage, macular edema, or subretinal, sub-RPE or intraretinal fluid) at Baseline. 6. The total area of fibrosis in the study eye comprising less than 50% of the lesion area. Patient subgroup specific inclusion criteria Patients need to meet all the criteria for one of the following two groups: Group 1. Primary treatment failure 7. No prior anti-VEGF treatment prior to initiating aflibercept. 8. Received no more than 3 injections of aflibercept into the study eye prior to the Screening Visit. 9. Historical OCT volume scan acquired =65 years) yes F.1.3.1 Number of subjects for this age range 109
Exclusion criteria
Exclusion criteria: Exclusion criteria for patient 1. Inability to comply with study or follow-up procedures. 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 3. 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. Exclusion criteria for systemic medical history and conditions 4. History of cerebrovascular accident, transient ischemic attack or myocardial infarction within 3 months of the Screening visit. 5. Any type of systemic disease or its treatment, 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. 6. Uncontrolled blood pressure defined as a persistent systolic value of >160 mm Hg or persistent diastolic value of >100 mm Hg at Screening or Baseline. 7. Simultaneous participation in any other clinical study for the duration of this study. 8. Use of other investigational drugs (excluding vitamins and minerals) or participation in any other clinical study within 90 days or 5 half-lives of the Screening visit, or until the expected pharmacodynamic effect has resolved, whichever is longer. 9. History of hypersensitivity to either ranibizumab (or any component of the ranibizumab formulation), or fluorescein, or indocyanine green, or to drugs of similar chemical classes. Exclusion criteria for ocular medical history and conditions For either eye 10. Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of Screening or Baseline. 11. Uncontrolled glaucoma (intraocular pressure [IOP] =30 mm Hg on medication or according to Investigator’s judgment) at the time of Screening or Baseline. 12. Evidence of bilateral active CNV during the Screening Period or at Baseline requiring bilateral anti-VEGF injections. Patients with active CNV in the study eye with quiescent CNV in the fellow eye who may have received IVT aflibercept or ranibizumab injections into the fellow eye >40 days prior to the Screening visit are not excluded from the study; however, should the fellow eye require anti-VEGF treatment during the study only ranibizumab may be utilized. 13. Prior intravitreal injection of ranibizumab or bevacizumab into the study eye and/or prior intravitreal injection of bevacizumab into the fellow eye Study eye exclusion criteria 14. At Baseline, intraocular surgery was performed within the previous 28 days or intraocular surgery is planned at any time during the 6 month study period. 15. Cataract (if causing significant visual impairment), aphakia, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause for CNV other than wet AMD (e.g., ocular histoplasmosis, pathologic myopia (=-8 dioptres)) at the time of Screening and Baseline. 16. Irreversible structural damage involving the center of the fovea (e.g. advanced fibrosis or geographic atrophy) which in the opinion of the Investigator is sufficient to irreversibly impair visual acuity. 17. Polypoidal chor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate whether treatment with intravitreal ranibizumab is associated with improvement (i.e. reduction at Day 90 from Baseline) in central subfield retinal thickness (CSRT) as determined by spectral domain/high definition optical coherence tomography (SD/HD-OCT) after 3 monthly injections of ranibizumab. The CSRT represents the average retinal thickness (µm) of the circular area within 1 mm diameter around the foveal center.;Secondary Objective: To evaluate whether treatment with intravitreal ranibizumab is associated with improvements in various retinal morphology parameters as determined by SD/HD-OCT at various time points over a period of 6 months and evaluated by the Central Reading Centre (CRC) including: - The change in subfoveal retinal thickness (SRT), central subfield retinal thickness (CSRT) and central subfield retinal volume (CSRV). - The proportion of patients with subretinal fluid (SF), intra-retinal cystoid changes (IRC), pigment epithelial detachments (PEDs), or dry retina. - The change in size (height or volume as appropriate) of various anatomical parameters including SF, IRC, and PEDs. To evaluate changes from Baseline BCVA at various time points over a period of 6 months including changes in BCVA between 3 and 6 months. To evaluate ocular and systemic safety by determining the incidence of ocular and systemic adverse events (AEs) up to Day 180. ;Primary end point(s): The primary objective is to demonstrate that the mean change from baseline in CSRT (as determined by OCT) at Day 90 is less than zero. The primary variable is the difference from baseline to Day 90 in CSRT.;Timepoint(s) of evaluation of this end point: Month 3 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine whether ranibizumab treatment is associated with improvements in various retinal morphology parameters as determined by OCT over a period of 6 months including: o The change in subfoveal retinal thickness (SRT), central subfield retinal thickness (CSRT) and central subfield retinal volume (CSRV). o The proportion of patients with subretinal fluid (SF), intra-retinal cystoid changes (IRC), pigment epithelial detachments (PEDs), or dry retina. o The change in size (height or volume as appropriate) of various anatomical parameters including SF, IRC, and PEDs. ? To evaluate changes from Baseline BCVA at various time points over a period of 6 months including changes in BCVA between 3 and 6 months. To evaluate ocular and systemic safety by determining the incidence of ocular and systemic adverse events (AEs).;Timepoint(s) of evaluation of this end point: Months 1-6 | — |
Countries
Germany, United Kingdom
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed