Clinical trial NCT02161575: Safety and Efficacy of Switching From Aflibercept to Ranibizumab in Patients With nAMD
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neovascular Age-related Macular Degeneration
Keywords: Macular degeneration
age-related macular degeneration (ARMD)
vision loss
macula damage
retina damage
dry macular degeneration
wet macular degeneration
AMD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-06-11
Enrollment: 103
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 90.
timeFrame: Baseline and Day 90
Secondary outcomes:
measure: Change in Subfoveal Retinal Thickness (SRT) From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Change in Central Subfield Retinal Volume (CSRV) From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Number of Patients With Intraretinal Fluid Assessed at Baseline and Day 180
timeFrame: Baseline and Day 180
measure: Number of Patients With Subretinal Fluid Assessed at Baseline and Day 180
timeFrame: Baseline to Day 180
measure: Number of Patients With Intraretinal/Subretinal Fluid Within the Central Subfield Fluid Assessed at Baseline and Day 180
timeFrame: Baseline and Day 180
measure: Number of Patients With Pigment Epithelial Detachments Assessed at Baseline and Day 180
timeFrame: Baseline and Day 180
measure: Number of Patients With Dry Retina Assessed at Baseline and Day 180
timeFrame: Baseline and Day 180
measure: Change in Maximum PED Height From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Change in Maximum PED Diameter From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Change in Maximum IRC Height From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Change in Best Corrected Visual Acuity (BCVA) in the Study Eye
timeFrame: Baseline, Day 90 and Day 180
measure: Change in ETDRS Letters for Study Eye From Baseline to Day 180
timeFrame: Baseline and Day 180
measure: Incidence of Ocular TEAEs in the Study Eye Reported by ≥2% Patients From Baseline to Day 180
timeFrame: Baseline to Day 180
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Karlsruhe
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Mühlheim
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Darlington
country: United Kingdom
facility: Novartis Investigative Site
state: Durham
city: Harlow
country: United Kingdom
facility: Novartis Investigative Site
state: Essex
city: Canterbury
country: United Kingdom
facility: Novartis Investigative Site
state: Kent
city: Aberdeen
country: United Kingdom
facility: Novartis Investigative Site
state: Scotland
city: Ipswich
country: United Kingdom
facility: Novartis Investigative Site
state: Suffolk
city: Frimley
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: East Kilbride
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Great Yarmouth
country: United Kingdom
facility: Novartis Investigative Site
city: Harrogate
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
city: Sunderland
country: United Kingdom
facility: Novartis Investigative Site
city: Uxbridge
country: United Kingdom
facility: Novartis Investigative Site
city: York
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Gale RP, Pearce I, Eter N, Ghanchi F, Holz FG, Schmitz-Valckenberg S, Balaskas K, Burton BJL, Downes SM, Eleftheriadis H, George S, Gilmour D, Hamilton R, Lotery AJ, Patel N, Prakash P, Santiago C, Thomas S, Varma D, Walters G, Williams M, Wolf A, Zakri RH, Igwe F, Ayan F. Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study. Br J Ophthalmol. 2020 Apr;104(4):493-499. doi: 10.1136/bjophthalmol-2019-314251. Epub 2019 Aug 5.