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

NCT02161575 | Completed Phase 4 Results

• 2 other identifiers: CRFB002AGB172014-001085-10
• Study Type: interventional
• Target: 103
• Locations: 2 countries
• Sites: 28

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change in Subfoveal Retinal Thickness (SRT) From Baseline to Day 180

  Baseline and Day 180

• Change in Central Subfield Retinal Thickness (CSRT) From Baseline to Day 180

  Baseline and Day 180

• Change in Central Subfield Retinal Volume (CSRV) From Baseline to Day 180

  Baseline and Day 180

• Number of Patients With Intraretinal Fluid Assessed at Baseline and Day 180

  Baseline and Day 180

• Number of Patients With Subretinal Fluid Assessed at Baseline and Day 180

  Baseline to Day 180

Study Arms (1)

Ranibizumab

EXPERIMENTAL

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

Interventions

Ranibizumab DRUG

Intraveal injections of 0.5mg ranibizumab

Ranibizumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

Novartis Investigative Site

Bonn, 53127, Germany

Location

Novartis Investigative Site

Karlsruhe, 76135, Germany

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Novartis Investigative Site

Leipzig, 04103, Germany

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Novartis Investigative Site

Mühlheim, 45468, Germany

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Novartis Investigative Site

München, 80336, Germany

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Novartis Investigative Site

Münster, 48149, Germany

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Novartis Investigative Site

Darlington, Durham, DL3 6HX, United Kingdom

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Novartis Investigative Site

Harlow, Essex, CM20 1QX, United Kingdom

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Novartis Investigative Site

Canterbury, Kent, CT1 3NG, United Kingdom

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Novartis Investigative Site

Aberdeen, Scotland, AB25 2ZN, United Kingdom

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Novartis Investigative Site

Ipswich, Suffolk, IP4 5PD, United Kingdom

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Novartis Investigative Site

Frimley, Surrey, GU16 7UJ, United Kingdom

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Novartis Investigative Site

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

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Novartis Investigative Site

Belfast, BT12 6BA, United Kingdom

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Novartis Investigative Site

East Kilbride, G75 8RG, United Kingdom

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Novartis Investigative Site

Glasgow, G12 OYN, United Kingdom

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Novartis Investigative Site

Great Yarmouth, NR31 6LA, United Kingdom

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Novartis Investigative Site

Harrogate, HG2 7SX, United Kingdom

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Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

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Novartis Investigative Site

London, EC1V 2PD, United Kingdom

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Novartis Investigative Site

London, NW1 5QH, United Kingdom

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Novartis Investigative Site

London, SE5 9RS, United Kingdom

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Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

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Novartis Investigative Site

Oxford, OX3 9DU, United Kingdom

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Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

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Novartis Investigative Site

Sunderland, SR2 9HP, United Kingdom

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Novartis Investigative Site

Uxbridge, UB8 3NN, United Kingdom

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Novartis Investigative Site

York, YO31 8HE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31383649 DERIVED

MeSH Terms

Conditions

Macular Degeneration; Vision Disorders; Geographic Atrophy; Wet Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 11, 2014
• Study Start: August 28, 2014
• Primary Completion: September 14, 2017
• Study Completion: September 14, 2017
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2019-02

Locations

DE (6); GB (22)