Study for Recalcitrant Age Related Macular Degeneration

Phase 4

Completed

Conditions: Age Related Macular Degeneration

Interventions: Drug: aflibercept 2.0 mg

Registration Number: NCT01543568

Lead Sponsor: David M. Brown, M.D.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
2.0 mg intravitreal Aflibercept	aflibercept 2.0 mg	open label, Subjects seen monthly \& given mandatory 2.0 mg aflibercept at baseline, months 1, 2 and 4. Pro re nata (PRN) retreatment at months 3 and 5 was performed upon evidence of disease on spectral domain-optical coherence tomography (SD-OCT)

Primary Outcome Measures

Name	Time	Method
The Number of Patients With no Fluid on OCT	6 months

Secondary Outcome Measures

Name	Time	Method
Mean Change in OCT Central Foveal Thickness	6 Months
Average Time to Resolution of Intraretinal Cysts and Sub Retinal Fluid on OCT	6 months
Mean Change in Visual Acuity (BCVA)	6 Months	Change in Early Treatment of Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS-BCVA) from baseline to month 6. BCVA is measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Quantitative Change in Area (μ) From Baseline in Choroidal Neovascular Lesion Characteristics/Size as Measured by FA/Fundus Photos	6 Months
Mean Number of 0.2 mg Aflibercept Injections Administered	at 6 months
The Percentage of Patients Who Lose > 15 Letters Visual Acuity	6 Months