Clinical trial NCT01543568: Study for Recalcitrant Age Related Macular Degeneration
Official title: AflibercepT for Subjects Who Are Incomplete Responders to mUltiple Intravitreal Injections of Ranibizumab, Anti-VegF (The TURF Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Age Related Macular Degeneration
Keywords: Age related Macular Degeneration
Recalcitrant Age Related Macular Degeneration
Lead sponsor: Greater Houston Retina Research
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2012-03-05
Enrollment: 46
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: 50 Patients with recalcitrant exudative age-related macular degeneration with a history of retinal or subretinal fluid after multiple intravitreal injections with ranibizumab 0.5mg and subsequently treated with ranibizumab 2.0mg, who are incomplete responders to 2.0mg of ranibizumab.

Detailed description: The rationale for the TURF trial is based on the greater binding affinity of VEGF Trap-eye, which theoretically may prove to be more effective for recalcitrant wet AMD and therefore may demonstrate a positive impact on visual acuity and the foveal anatomy of subjects who have a history of a less than optimal anatomical and visual response to multiple intravitreal injections of 2.0mg (super-dose) ranibizumab. Based on the anatomical data from the VIEW1 and VIEW2 trials, approximately 70% of VEGF-Trap eye patients had no evidence of fluid on OCT compared to approximately 55% of ranibizumab patients. One potential interpretation of this clinical data is that the increased binding affinity and longer half-life of VEGF-Trap eye result in the resolution of more fluid for a longer duration of effect.

Patients to be enrolled in this study have a history of requiring monthly dosing of ranibizumab 2.0mg to achieve maximum resolution of fluid on OCT and increased visual acuity. These patients initially showed minimal fluid resolution visual acuity gains while treated with Lucentis (0.5mg ranibizumab) and were subsequently treated with 2.0mg monthly. It is expected that treating these same patients with 2.0mg EYLEA™ (aflibercept injection for eye) will maintain the fluid resolution on OCT and visual acuity gains previously requiring a super-dose of ranibizumab.

Eligibility criteria: Inclusion Criteria:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study
* Age \> 50 years
* Choroidal neovascularization secondary to AMD
* History of treatment with 0.5mg ranibizumab followed by 2.0mg ranibizumab for AMD
* Best corrected visual acuity in the study eye between 20/20 to 20/400 using an ETDRS chart

Exclusion Criteria:

* Pregnancy (positive pregnancy test) or lactation
* Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
* Participation in another simultaneous medical investigation or trial
* Prior treatment with anti-VEGF therapy in the study eye within 28 days of baseline
* Prior treatment with PDT within the past 3 months or more than 4 prior PDT treatments.
* Presence of significant subfoveal fibrosis or atrophy.
* Prior treatment with intravitreal aflibercept injection
* Prior treatment with triamcinolone in the study eye within 6 months of BSL.
* Prior treatment with dexamethasone in the study eye within 30 days prior to BSL
* Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Baseline
* History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye
* Active intraocular inflammation (grade trace or above) in the study eye
* Current vitreous hemorrhage in the study eye
* History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
* Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
* Uncontrolled glaucoma in the study eye (defined as IOP ≥ 30 mmHg despite treatment with anti-glaucoma medication)
* History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment.
* History of allergy to fluorescein, ICG or iodine, not amenable to treatment
* History of retinal pigment epithelial tear or rip

Primary outcomes:
measure: The Number of Patients With no Fluid on OCT
timeFrame: 6 months
Secondary outcomes:
measure: Mean Change in OCT Central Foveal Thickness
timeFrame: 6 Months
measure: Average Time to Resolution of Intraretinal Cysts and Sub Retinal Fluid on OCT
timeFrame: 6 months
measure: The Percentage of Patients Who Lose > 15 Letters Visual Acuity
timeFrame: 6 Months
measure: Mean Change in Visual Acuity (BCVA)
timeFrame: 6 Months
measure: Quantitative Change in Area (μ) From Baseline in Choroidal Neovascular Lesion Characteristics/Size as Measured by FA/Fundus Photos
timeFrame: 6 Months
measure: Mean Number of 0.2 mg Aflibercept Injections Administered
timeFrame: at 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Retina Consultants of Houston
state: Texas
Study officials:
affiliation: Director Greater Houston Research
name: David M Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aflibercept (eylea) for age-related macular degeneration. Med Lett Drugs Ther. 2012 Feb 6;54(1383):9-10. No abstract available.
citation: Ohr M, Kaiser PK. Intravitreal aflibercept injection for neovascular (wet) age-related macular degeneration. Expert Opin Pharmacother. 2012 Mar;13(4):585-91. doi: 10.1517/14656566.2012.658368. Epub 2012 Feb 3.
citation: Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004 Dec 30;351(27):2805-16. doi: 10.1056/NEJMoa042760.
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citation: Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44. doi: 10.1056/NEJMoa062655.
citation: Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):331-5.
citation: Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006 Mar;113(3):363-372.e5. doi: 10.1016/j.ophtha.2005.11.019. Epub 2006 Feb 3.
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citation: Imamura Y, Fujiwara T, Spaide RF. Fundus autofluorescence and visual acuity in central serous chorioretinopathy. Ophthalmology. 2011 Apr;118(4):700-5. doi: 10.1016/j.ophtha.2010.08.017. Epub 2010 Nov 5.
citation: Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008 May;92(5):667-8. doi: 10.1136/bjo.2007.134874. Epub 2008 Mar 20.
citation: Kaiser PK. Vascular endothelial growth factor Trap-Eye for diabetic macular oedema. Br J Ophthalmol. 2009 Feb;93(2):135-6. doi: 10.1136/bjo.2008.144071. No abstract available.
citation: Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11393-8. doi: 10.1073/pnas.172398299. Epub 2002 Aug 12.
citation: Eyetech Study Group. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina. 2002 Apr;22(2):143-52. doi: 10.1097/00006982-200204000-00002.
citation: Wykoff CC, Brown DM, Maldonado ME, Croft DE. Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial). Br J Ophthalmol. 2014 Jul;98(7):951-5. doi: 10.1136/bjophthalmol-2013-304736. Epub 2014 Feb 11.