Myopia, Pathological
Conditions
Keywords
sham-controlled, pathologic myopia, mCNV, choroidal neovascularization, intravitreal injection, vision loss, macular damage
Brief summary
VEGF Trap-Eye will be tested for safety and efficacy in patients with vision loss due to choroidal neovascularization secondary to pathologic myopia. This will be a placebo-controlled trial. 3 out of 4 patients will receive an injection of VEGF Trap-Eye into the affected eye (and repeated injections if required), and 1 out of 4 patients will receive a sham injection requiring no needle stick, but making the patient unaware of whether or not he received active treatment. Outcome of the two treatment groups will be compared after 24 weeks. From week 24, sham patients may receive active treatment. Total duration of the study will be 48 weeks.
Interventions
BIOLOGICALVEGF Trap-Eye (BAY86-5321)
1 intravitreal injection of the experimental drug, followed by monthly re-injections if needed
PROCEDURENo Drug
Sham procedure NOT involving injection of any substance; patient´s eye is anesthetized and a syringe without needle gently pressed on the cornea
Sponsors
Regeneron Pharmaceuticals
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to read (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent form or a family member) and understand the informed consent form and willing to sign the informed consent form * Signed informed consent form. In Japan only, the informed consent form for a subject under the age of 20 years will require the co-signature of the subject's legally authorized representative. * Men and women ≥ 18 years of age * Myopia of greater than or equal to -6 D OR axial length of greater than or equal to 26.5 mm * Active subfoveal or juxtafoveal (within 1 to 199 μm of the center of the fovea) CNV secondary to pathologic myopia as defined by leakage on FA * Best-corrected visual acuity of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye at 4 meters * Decrease in vision in the study eye is determined by the investigator, using his/her medical judgment, to be primarily the result of the current active mCNV * Willing, committed, and able to return for all clinic visits and complete all study-related procedures
Exclusion criteria
* Only one functional eye * Ocular media of insufficient quality to obtain fundus and OCT images in the study eye * Greatest linear dimension (GLD) of the lesion in the study eye is greater than 12 disc areas * Recurrent mCNV in the study eye * Aphakia in the study eye * History or presence of CNV with an origin other than pathologic myopia in the study eye * Ocular inflammation or external ocular inflammation in the study eye * Concurrent disease in the study eye that would compromise BCVA or require medical or surgical intervention during the study period * Any ocular disorder in the study eye that, in the opinion of the investigator, may confound interpretation of the study results * Significant scarring or atrophy in the fovea that indicates substantial irreversible vision loss in the study eye * History of idiopathic or autoimmune-associated uveitis in either eye * Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection * Vitreomacular traction or traction retinal detachment, epiretinal membrane in either eye * Any iris neovascularization and/or vitreous hemorrhage in either eye * Uncontrolled glaucoma, or previous filtration surgery in either eye * Prior and concomitant treatments * In the study eye: * Any prior or concomitant treatment with another investigational agent for mCNV * Any previous panretinal photocoagulation or subfoveal thermal laser therapy * Any prior treatment with photodynamic therapy * Cataract surgery within 3 months prior to Day 1 * Yttrium-aluminum-garnet laser capsulotomy within 2 months prior to Day 1 * Any other intraocular surgery within 3 months prior to Day 1 * History of vitreoretinal surgery and/or scleral buckle surgery * Any prior treatment with anti-VEGF agents * Previous use of intraocular or periocular corticosteroids in either eye within 3 months prior to Day 1 * Previous assignment to treatment during this study * Uncontrolled hypertension * History of cerebrovascular disease or myocardial infarction within 6 months prior to Baseline/Day 1 * History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect interpretation of the results of the study, or renders the subject at high risk from treatment complications * Women of childbearing potential without contraception, women who intend to breastfeed during the study. All subjects (both men and women) of childbearing potential who are unwilling to use adequate birth control measures during the course of the study. * Renal failure requiring dialysis or renal transplant * Participation in an investigational study within 30 days prior to Screening/Visit 1 that involved treatment with any drug (excluding vitamins and minerals) or device * Known serious allergy to the fluorescein sodium for injection in angiography or Verteporfin * Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline to Week 24 - Last Observation Carried Forward (LOCF) | Baseline, Week 24 | Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases | Baseline, Week 24 | Data as observed at visit, no carrying forward from latest observation if missing data at later time points. Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. |
| Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF | Baseline, Week 24 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF | Baseline, Week 24 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF | Baseline, Week 48 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF | Baseline, Week 48 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF | Baseline, Week 48 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF | Baseline, Week 24 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF | Baseline, Week 24 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF | Baseline, Week 24 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF | Baseline, Week 48 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach | Baseline, Week 24 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF | Baseline, Week 48 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
| Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF | Baseline, Week 24 | A negative number indicates improvement (reduced thickness). |
| Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF | Baseline, Week 48 | A negative number indicates improvement (reduced thickness). |
| Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF | Baseline, Week 24 | CNV area values measured in square millimeters, each disc area is equivalent to 2.54 mm\^2 on the retina; lower values represent better outcomes |
| Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF | Baseline, Week 48 | CNV area values measured in square millimeters, each disc area is equivalent to 2.54 mm\^2 on the retina; lower values represent better outcomes |
| Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF | Baseline, Week 24 | EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best). |
| Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF | Baseline, Week 24 | The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight. |
| Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks | Baseline, Week 24 | — |
| Mean Change in Area of Leakage From Baseline at Week 24 - LOCF | Baseline, Week 24 | A negative change from baseline indicates improvement, ie, less leakage. |
| Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF | Baseline, Week 48 | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed. |
Countries
Hong Kong, Japan, Singapore, South Korea, Taiwan
Participant flow
Recruitment details
The study was conducted at 20 study centers in 5 countries. Recruitment period: 17 Dec 2010 - 28 Feb 2013.
Pre-assignment details
A total of 173 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham Participants received a single 2 mg dose of Intravitreal Aflibercept Injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) at baseline (Week 0). Following this, participants were monitored every 4 weeks and received an injection at these visits up to week 44 only if the Choroidal neovascularization (CNV) persisted or recurred, i.e. protocol defined re-treatment criteria were met. If these re-treatment criteria were not met at a given visit, participant received a sham injection. | 90 |
| Sham Treatment First, Then Aflibercept Injection or Sham Participant received a sham injection every 4 weeks from Week 0 to Week 20. At Week 24, participants received a single 2 mg Intravitreal Aflibercept Injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321). Following this, participants were monitored every 4 weeks and received an injection at these visits up to week 44 only if the Choroidal neovascularization (CNV) persisted or recurred, i.e. protocol defined re-treatment criteria were met. If these re-treatment criteria were not met at a given visit, participant received a sham injection. | 31 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | Aflibercept Injection First, Then Aflibercept or Sham | Sham Treatment First, Then Aflibercept Injection or Sham | Total |
|---|---|---|---|
| Age, Continuous | 58.5 Years STANDARD_DEVIATION 13.7 | 57.5 Years STANDARD_DEVIATION 12.1 | 58.2 Years STANDARD_DEVIATION 13.3 |
| Baseline area of leakage | 0.7005 disc area STANDARD_DEVIATION 0.683 | 0.6867 disc area STANDARD_DEVIATION 0.5563 | 0.6970 disc area STANDARD_DEVIATION 0.6507 |
| Baseline axial length | 28.791 millimeter (mm) STANDARD_DEVIATION 1.524 | 28.610 millimeter (mm) STANDARD_DEVIATION 1.696 | 28.745 millimeter (mm) STANDARD_DEVIATION 1.564 |
| Baseline Best Corrected Visual Acuity (BCVA) letter scores | 56.4 Letters correctly read STANDARD_DEVIATION 9.8 | 56.6 Letters correctly read STANDARD_DEVIATION 8.9 | 56.5 Letters correctly read STANDARD_DEVIATION 9.5 |
| Baseline Central Retinal Thickness by Optical Coherence Tomography (OCT) | 349.7 µm STANDARD_DEVIATION 91.3 | 354.2 µm STANDARD_DEVIATION 107.2 | 350.9 µm STANDARD_DEVIATION 95.2 |
| Baseline Choroidal neovascularization (CNV) size | 0.4086 disc area STANDARD_DEVIATION 0.5028 | 0.3334 disc area STANDARD_DEVIATION 0.3413 | 0.3894 disc area STANDARD_DEVIATION 0.4666 |
| Baseline intraocular pressure | 15.2 mm Hg STANDARD_DEVIATION 2.7 | 15.8 mm Hg STANDARD_DEVIATION 2.8 | 15.4 mm Hg STANDARD_DEVIATION 2.7 |
| Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) total score | 70.47 scores on a scale STANDARD_DEVIATION 13.48 | 72.73 scores on a scale STANDARD_DEVIATION 15.29 | 71.04 scores on a scale STANDARD_DEVIATION 13.94 |
| Duration of disease | 145.6 days STANDARD_DEVIATION 437.4 | 177.1 days STANDARD_DEVIATION 512 | 153.7 days STANDARD_DEVIATION 455.6 |
| European questionnaire 5 dimensions (EQ-5D) total score | 0.88 score on a scale STANDARD_DEVIATION 0.18 | 0.88 score on a scale STANDARD_DEVIATION 0.15 | 0.88 score on a scale STANDARD_DEVIATION 0.18 |
| Number of participants by category of time since mCNV diagnosis < 2 months | 73 Participants | 24 Participants | 97 Participants |
| Number of participants by category of time since mCNV diagnosis >= 2 months | 17 Participants | 7 Participants | 24 Participants |
| Race Asian | 90 Participants | 31 Participants | 121 Participants |
| Race Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 65 Participants | 27 Participants | 92 Participants |
| Sex: Female, Male Male | 25 Participants | 4 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 91 | 8 / 31 | 18 / 91 | 8 / 31 |
| serious Total, serious adverse events | 3 / 91 | 0 / 31 | 4 / 91 | 0 / 31 |
Outcome results
Primary
Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline to Week 24 - Last Observation Carried Forward (LOCF)
Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline to Week 24 - Last Observation Carried Forward (LOCF) | 12.1 Letters correctly read | Standard Deviation 8.3 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline to Week 24 - Last Observation Carried Forward (LOCF) | -2.0 Letters correctly read | Standard Deviation 9.7 |
Comparison: Null hypothesis was equality in change from baseline to Week 24 in BCVA total letter score between Eylea and Sham.p-value: <0.000195% CI: [10.8, 17.4]ANCOVA
Secondary
Mean Change in Area of Leakage From Baseline at Week 24 - LOCF
A negative change from baseline indicates improvement, ie, less leakage.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Area of Leakage From Baseline at Week 24 - LOCF | -0.4743 Disc areas | Standard Deviation 0.4839 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Area of Leakage From Baseline at Week 24 - LOCF | 0.2094 Disc areas | Standard Deviation 0.5088 |
p-value: <0.000195% CI: [-0.8056, -0.5239]ANCOVA
Secondary
Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases
Data as observed at visit, no carrying forward from latest observation if missing data at later time points. Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases | 12.0 Letters correctly read | Standard Deviation 8.4 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases | -0.8 Letters correctly read | Standard Deviation 9.3 |
p-value: <0.000195% CI: [9.4, 16.7]ANCOVA
Secondary
Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF
A negative number indicates improvement (reduced thickness).
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF | -79.1 microns | Standard Deviation 83.7 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF | -4.2 microns | Standard Deviation 127.4 |
p-value: <0.000195% CI: [-108.9, -46.9]ANCOVA
Secondary
Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF
A negative number indicates improvement (reduced thickness).
Time frame: Baseline, Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF | -83.1 microns | Standard Deviation 85.5 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF | -56.7 microns | Standard Deviation 119 |
p-value: 0.06595% CI: [-60.4, 1.8]ANCOVA
Secondary
Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF
CNV area values measured in square millimeters, each disc area is equivalent to 2.54 mm\^2 on the retina; lower values represent better outcomes
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF | -0.2233 Disc areas | Standard Deviation 0.3195 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF | 0.3007 Disc areas | Standard Deviation 0.4383 |
p-value: <0.000195% CI: [-0.599, -0.3626]ANCOVA
Secondary
Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF
CNV area values measured in square millimeters, each disc area is equivalent to 2.54 mm\^2 on the retina; lower values represent better outcomes
Time frame: Baseline, Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF | -0.1995 Disc areas | Standard Deviation 0.4281 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF | -0.0111 Disc areas | Standard Deviation 0.4031 |
p-value: 0.025695% CI: [-0.2525, -0.0167]ANCOVA
Secondary
Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF
EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best).
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF | 0.0187 Scores on a scale | Standard Deviation 0.1749 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF | 0.0341 Scores on a scale | Standard Deviation 0.1723 |
p-value: 0.86995% CI: [-0.0579, 0.049]ANCOVA
Secondary
Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF
The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF | 3.14 Scores on a scale | Standard Deviation 10.21 |
| Sham Treatment First, Then Aflibercept Injection or Sham | Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF | -2.58 Scores on a scale | Standard Deviation 10.07 |
p-value: 0.010495% CI: [1.25, 9.18]ANCOVA
Secondary
Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF | 63.3 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF | 12.9 Percentage of participants |
p-value: <0.00195% CI: [35, 66]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF | 68.9 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF | 41.9 Percentage of participants |
p-value: 0.007595% CI: [7.2, 46.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach | 38.9 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach | 9.7 Percentage of participants |
Comparison: Null hypothesis of difference of Eylea minus Sham of 0 was tested.p-value: 0.000195% CI: [14.4, 44]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF | 50.0 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF | 29.0 Percentage of participants |
p-value: 0.030895% CI: [1.9, 40.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF | 83.3 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF | 19.4 Percentage of participants |
p-value: <0.00195% CI: [47.8, 80.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF | 87.8 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF | 45.2 Percentage of participants |
p-value: <0.000195% CI: [23.7, 61.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF | 0 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF | 25.8 Percentage of participants |
p-value: 0.000695% CI: [-40.6, -11]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF | 1.1 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF | 22.6 Percentage of participants |
p-value: 0.003595% CI: [-35.9, -7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF | 0 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF | 6.5 Percentage of participants |
p-value: 0.147895% CI: [-15.2, 2.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF | 1.1 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF | 6.5 Percentage of participants |
p-value: 0.244695% CI: [-14.4, 3.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF | 3.3 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF | 35.5 Percentage of participants |
p-value: <0.000195% CI: [-48.1, -16.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Time frame: Baseline, Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF | 3.3 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF | 29.0 Percentage of participants |
p-value: 0.001295% CI: [-41.3, -10.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks
Time frame: Baseline, Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection First, Then Aflibercept or Sham | Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks | 6.7 Percentage of participants |
| Sham Treatment First, Then Aflibercept Injection or Sham | Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks | 19.4 Percentage of participants |