Neovascular Age-Related Macular Degeneration
Conditions
Keywords
nAMD
Brief summary
In this study researchers want to learn more about changes in visual acuity (clarity of vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood into the light sensitive lining inside the eye (retina). The fluid buildup causes the central part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken (edema), which distorts vision.
Interventions
DRUGAflibercept High Dose VEGF Trap-Eye (BAY86-5321)
Solution in Vial, intravitreal (IVT) injection
DRUGAflibercept VEGF Trap-Eye (Eylea, BAY86-5321)
Solution in Vial, 2 mg, intravitreal (IVT) injection
Sponsors
Regeneron Pharmaceuticals
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Up to Week 108: Participant and Investigator masked. Week 108 to Week 156: Participant and Investigator unmasked to treatment intervals.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye. * Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye. * BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye. * Decrease in BCVA determined to be primarily the result of nAMD in the study eye. * Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT. * Contraceptive use by men or women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical studies. * Other protocol-specified inclusion criteria. Additional inclusion criteria for Year 3: * At least one BCVA value and one central subfield retinal thickness (CST) value from measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or Visit 26 (Week 92). * Participant is enrolled at a site that participates in the extension period.
Exclusion criteria
* Causes of CNV other than nAMD in the study eye. * Scar, fibrosis, or atrophy involving the central subfield in the study eye. * Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye. * Uncontrolled glaucoma (defined as IOP \>25 mmHg despite treatment with anti-glaucoma medication) in the study eye. * History of idiopathic or autoimmune uveitis in the study eye. * Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery. * History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye. * Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization. * Uncontrolled blood pressure (defined as systolic \>160 mmHg or diastolic \>95 mmHg). * Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 | At baseline and Week 48 | Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 | At Week 16 | — |
| Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48 | At baseline and Week 48 | — |
| Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48 | At Week 48 | — |
| Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48 | At baseline and Week 48 | — |
| Change in Total Lesion Area From Baseline to Week 48 | At baseline and Week 48 | — |
| Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60 | At baseline and Week 60 | Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best). |
| Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48 | At baseline and Week 48 | — |
| Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48 | At baseline and Week 48 | NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems) |
| Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Up to Week 48 | — |
| Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Up to week 96 | — |
| Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48 | At Week 48 | — |
Countries
Argentina, Australia, Austria, Bulgaria, Canada, China, Czechia, Estonia, France, Georgia, Hungary, Israel, Italy, Japan, Latvia, Lithuania, Portugal, Russia, Serbia, Singapore, Slovakia, South Korea, Spain, Switzerland, Taiwan, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 251 centers in 27 countries/regions with first participant first visit on 20-AUG-2020 and last participant last visit (Week 156) on 07-Aug-2024.
Pre-assignment details
Overall, 1395 participants were screened, of whom 383 participants did not complete screening, 1 participant was randomized in error although he/she did not complete screening and had withdrawn consent. A total of 1011 participants were randomized in nearly equal numbers to 1 of the 3 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept 2q8 Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals, up to 96 weeks. | 336 |
| Aflibercept HDq12 Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals, up to 96 weeks. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria | 335 |
| Aflibercept HDq16 Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals, up to 96 weeks. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria | 338 |
| Total | 1,009 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Phase | Adverse Event | 2 | 3 | 1 |
| Extension Phase | Death | 4 | 7 | 2 |
| Extension Phase | Lack of Efficacy | 2 | 0 | 1 |
| Extension Phase | Logistical problems | 0 | 1 | 1 |
| Extension Phase | Lost to Follow-up | 0 | 2 | 3 |
| Extension Phase | Other | 1 | 0 | 0 |
| Extension Phase | Physician Decision | 1 | 0 | 1 |
| Extension Phase | Withdrawal by Subject | 11 | 11 | 7 |
| Main Study | Adverse Event | 9 | 5 | 8 |
| Main Study | COVID-19 pandemic | 2 | 2 | 2 |
| Main Study | Death | 10 | 7 | 7 |
| Main Study | Lack of Efficacy | 2 | 1 | 0 |
| Main Study | Lost to Follow-up | 3 | 3 | 4 |
| Main Study | Other | 7 | 3 | 2 |
| Main Study | Physician Decision | 3 | 3 | 2 |
| Main Study | Protocol Violation | 0 | 0 | 1 |
| Main Study | Withdrawal by Subject | 14 | 20 | 20 |
Baseline characteristics
| Characteristic | Total | Aflibercept HDq16 | Aflibercept 2q8 | Aflibercept HDq12 |
|---|---|---|---|---|
| Age, Continuous | 74.5 Years STANDARD_DEVIATION 8.4 | 74.5 Years STANDARD_DEVIATION 8.5 | 74.2 Years STANDARD_DEVIATION 8.8 | 74.7 Years STANDARD_DEVIATION 7.9 |
| Baseline BCVA measured by the ETDRS letter score | 59.6 scores on a scale STANDARD_DEVIATION 13.3 | 60.0 scores on a scale STANDARD_DEVIATION 12.4 | 58.9 scores on a scale STANDARD_DEVIATION 14 | 59.9 scores on a scale STANDARD_DEVIATION 13.4 |
| Baseline central subfield retinal thickness (CST) | 369.3 µm STANDARD_DEVIATION 130 | 370.7 µm STANDARD_DEVIATION 132.7 | 367.1 µm STANDARD_DEVIATION 133.6 | 370.3 µm STANDARD_DEVIATION 123.7 |
| Baseline choroidal neovascularization (CNV) size | 6.2946 mm² STANDARD_DEVIATION 5.1433 | 6.5459 mm² STANDARD_DEVIATION 5.5315 | 6.3593 mm² STANDARD_DEVIATION 5.0394 | 5.9768 mm² STANDARD_DEVIATION 4.8306 |
| Baseline NEI-VFQ-25 total score | 77.2733 scores on a scale STANDARD_DEVIATION 14.9843 | 77.6670 scores on a scale STANDARD_DEVIATION 15.398 | 77.8082 scores on a scale STANDARD_DEVIATION 14.4206 | 76.3575 scores on a scale STANDARD_DEVIATION 15.1213 |
| Baseline total lesion area | 6.7097 mm² STANDARD_DEVIATION 5.3827 | 6.8814 mm² STANDARD_DEVIATION 5.6514 | 6.8647 mm² STANDARD_DEVIATION 5.4145 | 6.3820 mm² STANDARD_DEVIATION 5.0664 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 9 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 970 Participants | 326 Participants | 322 Participants | 322 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 3 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 550 Participants | 180 Participants | 188 Participants | 182 Participants |
| Sex: Female, Male Male | 459 Participants | 158 Participants | 148 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 336 | 11 / 335 | 7 / 338 | 18 / 673 | 4 / 208 | 7 / 210 | 2 / 207 | 9 / 417 |
| other Total, other adverse events | 179 / 336 | 163 / 335 | 180 / 338 | 343 / 673 | 136 / 208 | 120 / 210 | 135 / 207 | 255 / 417 |
| serious Total, serious adverse events | 69 / 336 | 83 / 335 | 72 / 338 | 155 / 673 | 49 / 208 | 61 / 210 | 61 / 207 | 122 / 417 |
Outcome results
Primary
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48
Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best).
Time frame: At baseline and Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment. Estimand mainly based on hypothetical strategy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q8 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 | 7.03 scores on a scale | Standard Error 0.74 |
| Aflibercept HDq12 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 | 6.06 scores on a scale | Standard Error 0.77 |
| Aflibercept HDq16 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 | 5.89 scores on a scale | Standard Error 0.72 |
Comparison: HDq12 - 2q8p-value: 0.000995% CI: [-2.87, 0.92]Mixed Models Analysis
Comparison: HDq16 - 2q8p-value: 0.001195% CI: [-2.97, 0.69]Mixed Models Analysis
Secondary
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60
Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best).
Time frame: At baseline and Week 60
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment. Estimand mainly based on hypothetical strategy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q8 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60 | 7.23 scores on a scale | Standard Error 0.68 |
| Aflibercept HDq12 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60 | 6.37 scores on a scale | Standard Error 0.74 |
| Aflibercept HDq16 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60 | 6.31 scores on a scale | Standard Error 0.66 |
Comparison: HDq12 - 2q8p-value: 0.000295% CI: [-2.57, 0.84]Mixed Models Analysis
Comparison: HDq16 - 2q8p-value: <0.000195% CI: [-2.51, 0.66]Mixed Models Analysis
Secondary
Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48
Time frame: At baseline and Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q8 | Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48 | -136.25 µm | Standard Error 4.24 |
| Aflibercept HDq12 | Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48 | -147.37 µm | Standard Error 4.01 |
| Aflibercept HDq16 | Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48 | -146.76 µm | Standard Error 3.76 |
Comparison: HDq12 - 2q8p-value: 0.028395% CI: [-21.06, -1.18]Mixed Models Analysis
Comparison: HDq16 - 2q8p-value: 0.032195% CI: [-20.12, -0.9]Mixed Models Analysis
Secondary
Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48
NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)
Time frame: At baseline and Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q8 | Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48 | 4.22 scores on a scale | Standard Error 0.7 |
| Aflibercept HDq12 | Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48 | 3.50 scores on a scale | Standard Error 0.7 |
| Aflibercept HDq16 | Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48 | 3.35 scores on a scale | Standard Error 0.72 |
Comparison: HDq12 - 2q8p-value: 0.381795% CI: [-2.35, 0.9]Mixed Models Analysis
Comparison: HDq16 - 2q8p-value: 0.30795% CI: [-2.55, 0.8]Mixed Models Analysis
Secondary
Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48
Time frame: At baseline and Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q8 | Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48 | -2.43 mm^2 | Standard Error 0.31 |
| Aflibercept HDq12 | Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48 | -3.65 mm^2 | Standard Error 0.28 |
| Aflibercept HDq16 | Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48 | -2.91 mm^2 | Standard Error 0.29 |
Comparison: HDq12 - 2q8p-value: 0.000995% CI: [-1.94, -0.51]Mixed Models Analysis
Comparison: HDq16 - 2q8p-value: 0.207695% CI: [-1.22, 0.27]Mixed Models Analysis
Secondary
Change in Total Lesion Area From Baseline to Week 48
Time frame: At baseline and Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q8 | Change in Total Lesion Area From Baseline to Week 48 | 0.09 mm^2 | Standard Error 0.22 |
| Aflibercept HDq12 | Change in Total Lesion Area From Baseline to Week 48 | -0.46 mm^2 | Standard Error 0.19 |
| Aflibercept HDq16 | Change in Total Lesion Area From Baseline to Week 48 | -0.35 mm^2 | Standard Error 0.2 |
Comparison: HDq12 - 2q8p-value: 0.028795% CI: [-1.04, -0.06]Mixed Models Analysis
Comparison: HDq16 - 2q8p-value: 0.08795% CI: [-0.94, 0.06]Mixed Models Analysis
Secondary
Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response
Time frame: Up to week 96
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aflibercept 2q8 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Low (< 1000) | 8 Participants |
| Aflibercept 2q8 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - High (> 10000) | 0 Participants |
| Aflibercept 2q8 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Moderate (1000-10000) | 0 Participants |
| Aflibercept HDq12 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Low (< 1000) | 14 Participants |
| Aflibercept HDq12 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - High (> 10000) | 0 Participants |
| Aflibercept HDq12 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Moderate (1000-10000) | 0 Participants |
| Aflibercept HDq16 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Moderate (1000-10000) | 0 Participants |
| Aflibercept HDq16 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Low (< 1000) | 13 Participants |
| Aflibercept HDq16 | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - High (> 10000) | 0 Participants |
| All Aflibercept HD | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Low (< 1000) | 27 Participants |
| All Aflibercept HD | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - High (> 10000) | 0 Participants |
| All Aflibercept HD | Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response | Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Moderate (1000-10000) | 0 Participants |
Secondary
Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48
Time frame: At Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.~The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to 1 participant per each treatment group with no post-baseline BCVA. These participants with missing assessments were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept 2q8 | Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48 | 57.9 Percentage of participants |
| Aflibercept HDq12 | Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48 | 56.9 Percentage of participants |
| Aflibercept HDq16 | Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48 | 54.3 Percentage of participants |
Comparison: HDq12 - 2q8p-value: 0.955495% CI: [-6.565, 6.2]Cochran-Mantel-Haenszel
Comparison: HDq16 - 2q8p-value: 0.483495% CI: [-8.435, 3.994]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48
Time frame: At baseline and Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.~The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to 1 participant per each treatment group with no post-baseline BCVA. These participants with missing assessments were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept 2q8 | Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48 | 22.1 Percentage of participants |
| Aflibercept HDq12 | Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48 | 20.7 Percentage of participants |
| Aflibercept HDq16 | Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48 | 21.7 Percentage of participants |
Comparison: HDq12 - 2q8p-value: 0.570495% CI: [-7.784, 4.287]Cochran-Mantel-Haenszel
Comparison: HDq16 - 2q8p-value: 0.761195% CI: [-6.997, 5.119]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16
Time frame: At Week 16
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment. Estimand mainly based on hypothetical strategy.~The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to missing assessment at the respective visit. These participants with missing assessments were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept 2q8 | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 | 51.6 Percentage of participants |
| Aflibercept HDq12 | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 | 61.6 Percentage of participants |
| Aflibercept HDq16 | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 | 65.0 Percentage of participants |
| All Aflibercept HD | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 | 63.3 Percentage of participants |
Comparison: All HD - 2q8p-value: 0.000295% CI: [5.263, 18.204]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48
Time frame: At Week 48
Population: Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.~The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to missing assessments at the respective visit. These participants with missing assessments were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept 2q8 | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48 | 59.4 Percentage of participants |
| Aflibercept HDq12 | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48 | 71.1 Percentage of participants |
| Aflibercept HDq16 | Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48 | 66.8 Percentage of participants |
Comparison: HDq12 - 2q8p-value: 0.001595% CI: [4.527, 18.923]Cochran-Mantel-Haenszel
Comparison: HDq16 - 2q8p-value: 0.045895% CI: [0.142, 14.76]Cochran-Mantel-Haenszel
Secondary
Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48
Time frame: Up to Week 48
Population: Pharmacokinetic analysis set: included all participants who received any study treatment and who had at least 1 non-missing drug concentration measurement following the first dose of study treatment
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Aflibercept 2q8 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 28 | NA mg/L | — |
| Aflibercept 2q8 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 48 | NA mg/L | — |
| Aflibercept 2q8 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Visit 5: within 3 to 7 days after the Week 8 | 0.03 mg/L | Geometric Coefficient of Variation 70.29 |
| Aflibercept 2q8 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 4 | NA mg/L | — |
| Aflibercept 2q8 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 12 | NA mg/L | — |
| Aflibercept HDq12 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 4 | NA mg/L | — |
| Aflibercept HDq12 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 28 | NA mg/L | — |
| Aflibercept HDq12 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Visit 5: within 3 to 7 days after the Week 8 | 0.14 mg/L | Geometric Coefficient of Variation 78.69 |
| Aflibercept HDq12 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 48 | NA mg/L | — |
| Aflibercept HDq12 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 12 | 0.02 mg/L | Geometric Coefficient of Variation 81.35 |
| Aflibercept HDq16 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 48 | NA mg/L | — |
| Aflibercept HDq16 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 4 | NA mg/L | — |
| Aflibercept HDq16 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Visit 5: within 3 to 7 days after the Week 8 | 0.13 mg/L | Geometric Coefficient of Variation 82.5 |
| Aflibercept HDq16 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 12 | 0.02 mg/L | Geometric Coefficient of Variation 84.06 |
| Aflibercept HDq16 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 | Week 28 | NA mg/L | — |