Safety and Efficacy of Switching From Aflibercept to Ranibizumab in Patients With nAMD

Neovascular Age-related Macular Degeneration Clinical Trial

— SAFARI  

Official title:

A Phase IV, Prospective, Open-label, Uncontrolled, European Study in Patients With Neovascular Age-related Macular Degeneration (nAMD), Evaluating the Efficacy and Safety of Switching From Intravitreal Aflibercept to Ranibizumab 0.5mg.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02161575
• Other study ID #: CRFB002AGB17
• Secondary ID: 2014-001085-10
• Status: Completed
• Phase: Phase 4
• Start date: August 28, 2014
• Est. completion date: September 14, 2017

Study information

• Verified date: February 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

AMD (Age Related Macular Degeneration) is the leading cause of severe visual loss and blindness registration in the UK . It is a disease which affects the retina (the nerve and blood vessel network at the back of the eye responsible for vision). Patients can suffer with severe visual loss and have difficulties with every day tasks such as recognising faces, reading & driving.

There are two variations of the disease, a 'dry' type & a 'wet' type also known as neovascular AMD (nAMD). In wet/nAMD new vessels grow from the blood supply underneath the retina, in part due to higher than normal levels of a protein called Vascular Endothelial Growth Factor (VEGF). Since the introduction of drugs which block VEGF, visual outcomes for patients with wAMD have dramatically improved.

There are 2 widely used treatments; ranibizumab and aflibercept. Whilst the majority of patients have a successful outcome with treatment, many patients experience suboptimal response. This study evaluated if these patients experience a benefit from a switch to a different antiVEGF drug treatment.

In this study nAMD patients who are showing no or poor to response to treatment with aflibercept were switched to ranibizumab to assess if there is any benefit in terms of treatment outcomes.

Patients visited the hospital clinic 8 times over the 7 - 8 month study period. Monthly ranibizumab injections were given for the first 3 months, then monthly as required for the next 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: September 14, 2017
• Est. primary completion date: September 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Best corrected visual acuity (BCVA) =23 ETDRS letters in study eye

• Evidence of active choroidal neovascularisation (CNV) involving the center of the fovea in study eye Patient subgroup specific inclusion criteria: - Group 1. Primary treatment failure

• Initiated treatment with aflibercept <130 days prior to the Screening Visit.

• No increase in BCVA (=5 letters) since commencing treatment with aflibercept.

• Disease activity has never been controlled in the study eye after initiating aflibercept as defined by at least one of the following: evidence of unchanged or increasing retinal or subretinal fluid; new PED; unchanged or increasing size of preexisting PED.

Group 2. Suboptimal treatment response

• Aflibercept commenced =6 months prior to the Screening Visit.

• Received =3 aflibercept injections into the study eye within 6 months of the Screening Visit.

• Evidence of previous reduced disease activity (as defined by reduction of =50µm in Central Subfield Retinal Thickness on OCT) noted in the study eye after initiating aflibercept.

• At Screening Visit, disease activity has worsened (as defined by increasing retinal* or subretinal fluid, or new or increasing size of PED) in the study eye compared to prior visits.

Exclusion Criteria:

• History of cerebrovascular accident, transient ischemic attack or myocardial infarction within 3 months of the Screening visit.

• Uncontrolled blood pressure

• Evidence of bilateral active CNV during the Screening Period or at Baseline requiring bilateral antiVEGF injections.

• Prior intravitreal injection of ranibizumab or bevacizumab into the study eye and/or prior intravitreal injection of bevacizumab into the fellow eye.

• Cataract (if causing significant visual impairment), aphakia, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause than wet AMD (e.g. ocular histoplasmosis, pathologic myopia (=8 dioptres)) at the time of Screening and Baseline.

• 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.

• Polypoidal choroidal vasculopathy (PCV), RPE tear, central serous retinopathy (CSR), or significant vitreomacular traction identified during Screening period or within 4 months of Baseline visit.

• Unable to obtain at Screening OCT images of sufficient quality to be analyzed

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• Ranibizumab
Intraveal injections of 0.5mg ranibizumab

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Mühlheim
Germany	Novartis Investigative Site	München
United Kingdom	Novartis Investigative Site	Aberdeen	Scotland
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Canterbury	Kent
United Kingdom	Novartis Investigative Site	Darlington	Durham
United Kingdom	Novartis Investigative Site	East Kilbride
United Kingdom	Novartis Investigative Site	Frimley	Surrey
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Great Yarmouth
United Kingdom	Novartis Investigative Site	Harlow	Essex
United Kingdom	Novartis Investigative Site	Harrogate
United Kingdom	Novartis Investigative Site	Ipswich	Suffolk
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Southampton
United Kingdom	Novartis Investigative Site	Sunderland
United Kingdom	Novartis Investigative Site	Uxbridge
United Kingdom	Novartis Investigative Site	York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 90.	Measurement of the change in CSRT, determined by high definition optical coherence tomography (HD-OCT) after 3 monthly injections of ranibizumab. OCT is a non-invasive technique which can determine and measure thickness of the retina. A negative change from Baseline indicates an improvement (less retinal fluid and lower disease activity). Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 90
Secondary	Change in Subfoveal Retinal Thickness (SRT) From Baseline to Day 180	Measurement of change in SRT from Baseline to Day 180 as determined by high definition optical coherence tomography (HD-OCT). A reduction indicates an improvement in overall disease activity. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 180	Measurement of change in CSRT from Baseline to Day 180 as determined by high definition optical coherence tomography (HD-OCT). A reduction indicates an improvement in overall disease activity. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Change in Central Subfield Retinal Volume (CSRV) From Baseline to Day 180	Measurement of change in CSRV from Baseline to Day 180 as determined by high definition optical coherence tomography (HD-OCT). A reduction indicates an improvement in overall disease activity. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Number of Patients With Intraretinal Fluid Assessed at Baseline and Day 180	Presence or absence of qualitative OCT parameter Intraretinal Fluid. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Number of Patients With Subretinal Fluid Assessed at Baseline and Day 180	Presence or absence of qualitative OCT parameter Subretinal Fluid. Data collected on the study eye were used for the evaluation of efficacy.	Baseline to Day 180
Secondary	Number of Patients With Intraretinal/Subretinal Fluid Within the Central Subfield Fluid Assessed at Baseline and Day 180	Presence or absence of qualitative OCT parameter Intraretinal/Subretinal Fluid Within the Central Subfield. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Number of Patients With Pigment Epithelial Detachments Assessed at Baseline and Day 180	Presence or absence of qualitative OCT parameter Pigment Epithelial Detachments. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Number of Patients With Dry Retina Assessed at Baseline and Day 180	Presence or absence of qualitative OCT parameter Dry Retina. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Change in Maximum PED Height From Baseline to Day 180	Change from Baseline to Day 180 in Maximum Pigment Epithelial Detachment (PED) Height. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Change in Maximum PED Diameter From Baseline to Day 180	Change from Baseline to Day 180 in Maximum Pigment Epithelial Detachment (PED) Diameter. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Change in Maximum IRC Height From Baseline to Day 180	Change from Baseline to Day 180 in Maximum Intraretinal Cyst (IRC) Height. Data collected on the study eye were used for the evaluation of efficacy.	Baseline and Day 180
Secondary	Change in Best Corrected Visual Acuity (BCVA) in the Study Eye	BCVA was assessed as letters read and measured in a sitting position using subjective refraction and Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters.	Baseline, Day 90 and Day 180
Secondary	Change in ETDRS Letters for Study Eye From Baseline to Day 180	Number of patients gaining at least 15 letters from Baseline to Day 180	Baseline and Day 180
Secondary	Incidence of Ocular TEAEs in the Study Eye Reported by =2% Patients From Baseline to Day 180	Incidence of ocular Treatment Emergent Adverse Events (TEAEs) in the study eye reported by =2% patients by preferred term.	Baseline to Day 180