Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02161575
Recruitment Status : Completed
First Posted : June 11, 2014
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Neovascular Age-related Macular Degeneration Drug: Ranibizumab Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : August 28, 2014
Actual Primary Completion Date : September 14, 2017
Actual Study Completion Date : September 14, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Ranibizumab

Arm Intervention/treatment
Experimental: Ranibizumab
All patients received 3 monthly intraveal injections of 0.5mg ranibizumab followed by monthly injections of ranibizumab 0.5mg for a further 3 months on a prn (as required) basis, as determined by the study doctor.
Drug: Ranibizumab
Intraveal injections of 0.5mg ranibizumab




Primary Outcome Measures :
  1. Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 90. [ Time Frame: Baseline and 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.


Secondary Outcome Measures :
  1. Change in Subfoveal Retinal Thickness (SRT) From Baseline to Day 180 [ Time Frame: Baseline and 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.

  2. Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 180 [ Time Frame: Baseline and 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.

  3. Change in Central Subfield Retinal Volume (CSRV) From Baseline to Day 180 [ Time Frame: Baseline and 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.

  4. Number of Patients With Intraretinal Fluid Assessed at Baseline and Day 180 [ Time Frame: 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.

  5. Number of Patients With Subretinal Fluid Assessed at Baseline and Day 180 [ Time Frame: Baseline to Day 180 ]
    Presence or absence of qualitative OCT parameter Subretinal Fluid. Data collected on the study eye were used for the evaluation of efficacy.

  6. Number of Patients With Intraretinal/Subretinal Fluid Within the Central Subfield Fluid Assessed at Baseline and Day 180 [ Time Frame: 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.

  7. Number of Patients With Pigment Epithelial Detachments Assessed at Baseline and Day 180 [ Time Frame: 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.

  8. Number of Patients With Dry Retina Assessed at Baseline and Day 180 [ Time Frame: 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.

  9. Change in Maximum PED Height From Baseline to Day 180 [ Time Frame: Baseline and 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.

  10. Change in Maximum PED Diameter From Baseline to Day 180 [ Time Frame: Baseline and 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.

  11. Change in Maximum IRC Height From Baseline to Day 180 [ Time Frame: Baseline and 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.

  12. Change in Best Corrected Visual Acuity (BCVA) in the Study Eye [ Time Frame: Baseline, Day 90 and Day 180 ]
    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.

  13. Change in ETDRS Letters for Study Eye From Baseline to Day 180 [ Time Frame: Baseline and Day 180 ]
    Number of patients gaining at least 15 letters from Baseline to Day 180

  14. Incidence of Ocular TEAEs in the Study Eye Reported by ≥2% Patients From Baseline to Day 180 [ Time Frame: Baseline to Day 180 ]
    Incidence of ocular Treatment Emergent Adverse Events (TEAEs) in the study eye reported by ≥2% patients by preferred term.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02161575


Locations
Layout table for location information
Germany
Novartis Investigative Site
Bonn, Germany, 53127
Novartis Investigative Site
Karlsruhe, Germany, 76135
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
Mühlheim, Germany, 45468
Novartis Investigative Site
München, Germany, 80336
United Kingdom
Novartis Investigative Site
Darlington, Durham, United Kingdom, DL3 6HX
Novartis Investigative Site
Harlow, Essex, United Kingdom, CM20 1QX
Novartis Investigative Site
Canterbury, Kent, United Kingdom, CT1 3NG
Novartis Investigative Site
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Novartis Investigative Site
Ipswich, Suffolk, United Kingdom, IP4 5PD
Novartis Investigative Site
Frimley, Surrey, United Kingdom, GU16 7UJ
Novartis Investigative Site
Bradford, West Yorkshire, United Kingdom, BD9 6RJ
Novartis Investigative Site
Belfast, United Kingdom, BT12 6BA
Novartis Investigative Site
East Kilbride, United Kingdom, G75 8RG
Novartis Investigative Site
Glasgow, United Kingdom, G12 OYN
Novartis Investigative Site
Great Yarmouth, United Kingdom, NR31 6LA
Novartis Investigative Site
Harrogate, United Kingdom, HG2 7SX
Novartis Investigative Site
Liverpool, United Kingdom, L7 8XP
Novartis Investigative Site
London, United Kingdom, EC1V 2PD
Novartis Investigative Site
London, United Kingdom, NW1 5QH
Novartis Investigative Site
London, United Kingdom, SE5 9RS
Novartis Investigative Site
Manchester, United Kingdom, M13 9WL
Novartis Investigative Site
Oxford, United Kingdom, OX3 9DU
Novartis Investigative Site
Southampton, United Kingdom, SO16 6YD
Novartis Investigative Site
Sunderland, United Kingdom, SR2 9HP
Novartis Investigative Site
Uxbridge, United Kingdom, UB8 3NN
Novartis Investigative Site
York, United Kingdom, YO31 8HE
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] May 11, 2016
Statistical Analysis Plan  [PDF] October 12, 2017


Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02161575     History of Changes
Other Study ID Numbers: CRFB002AGB17
2014-001085-10 ( EudraCT Number )
First Posted: June 11, 2014    Key Record Dates
Results First Posted: February 15, 2019
Last Update Posted: February 15, 2019
Last Verified: February 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Macular degeneration
age-related macular degeneration (ARMD)
vision loss
macula damage
retina damage
dry macular degeneration
wet macular degeneration
AMD
Additional relevant MeSH terms:
Layout table for MeSH terms
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents