Age Related Macular Degeneration
Conditions
Keywords
Age related Macular Degeneration, Recalcitrant Age Related Macular Degeneration
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.
Interventions
Intravitreal aflibercept injection 2.0 mg
Sponsors
Regeneron Pharmaceuticals
David M. Brown, M.D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Number of Patients With no Fluid on OCT | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Time to Resolution of Intraretinal Cysts and Sub Retinal Fluid on OCT | 6 months | — |
| The Percentage of Patients Who Lose > 15 Letters Visual Acuity | 6 Months | — |
| Mean Change in OCT Central Foveal Thickness | 6 Months | — |
| 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 | — |
| 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. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from March 2012 to September 2012. 50 subjects from 1 site of the United States from a medical clinic. Each subject was was over 50 years of age, diagnosed with choroidal neovascularization secondary to AMD, and had a history of treatment with 0.5 mg ranibizumab followed by 2.0 mg ranibizumab for AMD.
Participants by arm
| Arm | Count |
|---|---|
| 2.0 mg Intravitreal Aflibercept 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)
aflibercept 2.0 mg: Intravitreal aflibercept injection 2.0 mg | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | 2.0 mg Intravitreal Aflibercept |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 41 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 77.8 years |
| Gender Female | 24 Participants |
| Gender Male | 22 Participants |
| Region of Enrollment United States | 46 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 45 |
| serious Total, serious adverse events | 9 / 45 |
Outcome results
Primary
The Number of Patients With no Fluid on OCT
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.0 mg Intravitreal Aflibercept | The Number of Patients With no Fluid on OCT | 10 participants |
Secondary
Average Time to Resolution of Intraretinal Cysts and Sub Retinal Fluid on OCT
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 2.0 mg Intravitreal Aflibercept | Average Time to Resolution of Intraretinal Cysts and Sub Retinal Fluid on OCT | 4 months |
Secondary
Mean Change in OCT Central Foveal Thickness
Time frame: 6 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 2.0 mg Intravitreal Aflibercept | Mean Change in OCT Central Foveal Thickness | -27.3 micrometers |
Secondary
Mean Change in Visual Acuity (BCVA)
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.
Time frame: 6 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 2.0 mg Intravitreal Aflibercept | Mean Change in Visual Acuity (BCVA) | 0.2 ETDRS BCVA letters |
Secondary
Mean Number of 0.2 mg Aflibercept Injections Administered
Time frame: at 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 2.0 mg Intravitreal Aflibercept | Mean Number of 0.2 mg Aflibercept Injections Administered | 5.6 injections |
Secondary
Quantitative Change in Area (μ) From Baseline in Choroidal Neovascular Lesion Characteristics/Size as Measured by FA/Fundus Photos
Time frame: 6 Months
Population: Given lack of visual benefit upon switching to aflibercept (Eylea), such analyses were not performed.
Secondary
The Percentage of Patients Who Lose > 15 Letters Visual Acuity
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.0 mg Intravitreal Aflibercept | The Percentage of Patients Who Lose > 15 Letters Visual Acuity | 0 Percentage of patients |