Macular Edema Secondary to Retinal Vein Occlusion
Conditions
Brief summary
Researchers are looking for a better way to treat people who have macular edema secondary to retinal vein occlusion (RVO). In people with RVO, a blood vessel that carries blood away from the retina (vein) becomes blocked. The retina is the very back part of the eye. The blocked vein causes fluid and blood to leak into the retina and thereby causes a swelling of the macula (the center of the retina responsible for fine vision). This swelling is called macular edema. When a vein in the retina is blocked, the levels of a protein called vascular endothelial growth factor (VEGF) rises. VEGF helps the growth of new blood vessels. This can lead to macular edema and may cause the vision to become blurry. The study treatment intravitreal (IVT) aflibercept is given as an injection into the eye. It works by blocking VEGF and this can help repair vision problems related to RVO. IVT aflibercept is already available and is prescribed by doctors as the standard of care treatment for macula edema secondary to RVO. Standard of care is a treatment that medical experts consider most appropriate for a disease. Standard of care is given every 4 weeks in people with macula edema secondary to RVO. While repeated injections of aflibercept may prevent worsening of vision, it may place a burden on the patient. However, a higher amount (8 mg) compared to the standard of care (2 mg) of IVT aflibercept is being tested in studies. This higher amount could be given less often. The amount of IVT aflibercept given is measured in milligrams, also known as mg. The main purpose of this study is to learn how well a higher amount of the study treatment aflibercept works in people with macular edema secondary to RVO. To answer this, researchers will measure changes in vision called best corrected visual acuity (BCVA) in the study participants between study start and after 36 weeks of treatment. Changes will then be compared between those participants who received the higher amount of IVT aflibercept and those that received standard of care. To learn how safe the study treatment is in the participants, the researchers will count the number of participants from study start and up to 64 weeks later that have: * adverse events * serious adverse events Adverse events are any medical problems that the participants have during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think they might be related to the study treatments. An adverse event is considered serious when it leads to death, puts the participants' lives at risk, requires hospitalization, causes disability, causes a baby being born with medical problems or is otherwise medically important. Dependent on the treatment group, the participants will either receive the higher amount of aflibercept or standard of care as an intravitreal injection for up to 60 weeks. The study will consist of a test (screening) phase, a treatment phase and an end of study phase. Each participant will be in the study for up to 64 weeks. One visit to the study site is planned during the screening phase, followed by visits approximately every 4 weeks (16 in total) during treatment and one visit at the end of the study. During the study, the study doctors and their team will: * check patients' eye health using various eye examination techniques * measure patients' eye vision (BCVA) * take blood and urine samples * do physical examinations * check vital signs * examine heart health using electrocardiogram (ECG) * do pregnancy tests in women of childbearing age In addition, participants will be asked to fill a questionnaire on vision-related quality of life.
Interventions
DRUGAflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_higher dose
Intravitreally (IVT) injection.
DRUGAflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_2 mg
Intravitreally (IVT) injection.
DRUGSham
Sham procedure will be given on visits when an active injection is not planned.
DIAGNOSTIC_TESTFluorescein
Fluorescein 100 mg/mL solution for injection is a dye that makes the retinal vessels visible during FA examinations, and as such, it will be used as an auxiliary medicinal product (AxMP) in this periodic ophthalmic examination. This medicine is for diagnostic use only. It is not used to treat any condition.
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
* Adult ≥18 years of age (or country's legal age of adulthood if the legal age is \>18 years) at the time of signing the informed consent. * Treatment-naïve macular edema involving the foveal center secondary to RVO (BRVO, HRVO, or CRVO) diagnosed within 16 weeks (112 days) before the screening visit in the study eye. * Early Treatment Diabetic Retinopathy Study BCVA letter score of 73 to 24 (20/40 to 20/320) at screening and baseline visits in the study eye. Decrease in BCVA determined to be primarily the result of RVO in the study eye. * Mean CST ≥300 μm on optical coherence tomography (OCT) if excluding Bruch's membrane (e.g., Cirrus or Topcon) or ≥320 μm if including Bruch's membrane (e.g., Heidelberg Spectralis), confirmed by the reading center at the screening visit and by the site at baseline visit in the study eye. * Capable of giving signed informed consent form (ICF) by study participant or legally acceptable representative, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. * US participants will be required to have a Health Insurance Portability and Accountability Act (HIPAA) authorization; in other countries, as applicable according to national laws. * Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for participation in clinical studies and fulfil the conditions set on Section 10.4.2.
Exclusion criteria
* Concurrent disease that causes substantial decrease of BCVA, is expected to limit BCVA recovery or is likely to require medical or surgical intervention during the study in the study eye. * Presence or history of the following ocular conditions: 1. Advanced age-related macular degeneration (neovascular AMD or geographic atrophy) in the study eye. 2. Diabetic macular edema or diabetic retinopathy, defined in diabetic participants as diabetic retinopathy lesions outside the area of the vein occlusion in the study eye and anywhere in the retina in the fellow eye. 3. Anterior segment neovascularization, vitreous hemorrhage, retinal detachment in the study eye. 4. Vitreomacular traction, epiretinal membrane or structural damage to the macula that is considered by the Investigator to significantly affect central vision or preclude improvement in vision in the study eye. 5. Macular hole of stage 2 and above in the study eye. 6. Myopia of a spherical equivalent of at least 8 diopters prior to any refractive or cataract surgery in the study eye. 7. Corneal transplant or corneal dystrophy in the study eye. 8. Idiopathic or autoimmune uveitis in the study or in the fellow eye. * Presence of the following ocular conditions at screening or baseline visit: 1. Significant media opacities, including cataract, that interfere with BCVA, or imaging assessments (e.g., fundus photography \[FP\], OCT) in the study eye. 2. Aphakia, or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium-aluminum-garnet \[YAG\] posterior capsulotomy performed more than 30 days before the screening visit), in the study eye. 3. Uncontrolled glaucoma (defined as IOP \>25 mmHg despite treatment with anti-glaucoma medication); or history or likely future need of glaucoma surgery in the study eye. 4. Intraocular inflammation/infection (including trace, or above, cells in the anterior chamber and/or vitreous) within 12 weeks (84 days) of the screening visit in the study or in the fellow eye. 5. Extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in the study or in the fellow eye. * Uncontrolled blood pressure (defined as systolic \>160 mmHg or diastolic \>95 mmHg) at the screening visit or baseline visit. * Uncontrolled diabetes mellitus, defined by hemoglobin A1c (HbA1c) \>12% at the screening visit. * History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) before the screening visit or between screening and baseline visits. * Renal failure requiring dialysis, or renal transplant at screening or potentially during the study. * Any prior or concomitant ocular or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for RVO in the study eye. * Previous administration of systemic anti-angiogenic medications for any condition. * Prior treatment of the study eye with any of the following drugs (any route of ophthalmic administration) or procedures: 1. Anti-angiogenic drugs at any time including investigational therapy (e.g., with anti-angiopoietin/anti-VEGF bispecific monoclonal antibodies). 2. Previous use topical steroids within 4 weeks (28 days) from the screening visit, or intraocular or periocular steroids within 16 weeks (112 days) from the screening visit, or steroid implants at any time. 3. Previous treatment with intraocular or periocular implant, gene therapy, or cell therapy at any time. 4. Treatment with ocriplasmin at any time. 5. Vitreoretinal surgery (including scleral buckling) at any time. 6. Any intraocular surgery, including cataract surgery, within 12 weeks (84 days) before the screening visit. 7. Previous treatment with retinal laser photocoagulation. * Prior treatment of the fellow eye with any of the following: a. Gene therapy, or cell therapy in the fellow eye at any time. * Participation in other clinical studies requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening visit, or within 30 days or 5 half-lives of administration of the previous study intervention, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 36 | At Week 36 | BCVA: Best-Corrected Visual Acuity; ETDRS: Early Treatment Diabetic Retinopathy Study; ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 36 | From baseline at Week 36 | — |
| Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 36 | At Week 36 | ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity) |
| Participants Having no Intraretinal Fluid (IRF) and no Sub-retinal Fluid (SRF) in the Center Subfield at Week 36 | At Week 36 | Number of participants with no retinal fluid (no IRF and no SRF) in the central subfield at Week 36 |
| Change From Baseline in Central Sub-field Thickness (CST) at Week 36 | From baseline to Week 36 | — |
| Number of Active Injections From Baseline to Week 36 | From baseline to Week 36 | Active injections refer to the number of injections that were actually administered, as opposed to the number of planned injections. |
| Participants Dosed Only Q8 Through Week 36 in the 8 mg Q8 Group | Through Week 36 | Number of participants in the aflibercept 8q8/3 and the aflibercept 8q8/5 groups who were able to maintain every 8 weeks (Q8) dosing through Week 36. Only participants who did not discontinue study intervention prior to Week 36, and were therefore considered completers for Week 36, were included in the analysis of this endpoint. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Through Week 36 | TEAEs were defined as AEs that occurred in the time frame from first injection (active or sham) to the last injection (active or sham) plus 30 days. Ocular TEAEs in study eye and non-ocular TEAEs are included (ocular TEAEs in fellow eye are excluded) |
| Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | From baseline through Week 36 | Total aflibercept is the sum of free and adjusted bound aflibercept. |
| Change From Baseline in NEI VFQ 25 Total Score at Week 36 | From baseline to Week 36 | NEI-VFQ-25: National Eye Institute Visual Functioning Questionnaire-25; The NEI VFQ-25 total score ranges from 0 to 100. A higher score means a better outcome (better patient-reported visual function). |
Countries
Australia, Austria, Bulgaria, China, Czechia, Estonia, France, Georgia, Germany, Hungary, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Poland, Portugal, Serbia, Slovakia, South Korea, Spain, Switzerland, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 237 centers in Europe, America, Japan, and Asia-Pacific between 15-May-2023 (first participant first visit) and 07-Nov-2024 (primary completion date).
Pre-assignment details
In total 1282 participants were screened, of whom 388 participants were screen failures. Overall, 892 participants were randomized and treated. Of these, 838 participants completed the treatment phase through Week 36 (primary completion date).
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept 2q4 Participants received aflibercept 2 mg administered every 4 weeks. | 301 |
| Aflibercept 8q8/3 Participants received aflibercept 8 mg administered every 8 weeks, after 3 initial injections at 4-week intervals. | 293 |
| Aflibercept 8q8/5 Participants received aflibercept 8 mg administered every 8 weeks, after 5 initial injections at 4-week intervals. | 298 |
| Total | 892 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Death | 2 | 2 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 | 2 |
| Overall Study | No information was available on whether follow-up was completed or not | 0 | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol deviation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 8 | 16 |
Baseline characteristics
| Characteristic | Aflibercept 2q4 | Aflibercept 8q8/3 | Aflibercept 8q8/5 | Total |
|---|---|---|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 11.7 | 65.8 Years STANDARD_DEVIATION 11.5 | 65.8 Years STANDARD_DEVIATION 11.5 | 65.9 Years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 25 Participants | 14 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 267 Participants | 254 Participants | 273 Participants | 794 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 14 Participants | 11 Participants | 37 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 101 Participants | 91 Participants | 97 Participants | 289 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 7 Participants | 9 Participants | 24 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not reported | 13 Participants | 22 Participants | 11 Participants | 46 Participants |
| Race/Ethnicity, Customized White | 178 Participants | 173 Participants | 177 Participants | 528 Participants |
| Sex: Female, Male Female | 144 Participants | 136 Participants | 146 Participants | 426 Participants |
| Sex: Female, Male Male | 157 Participants | 157 Participants | 152 Participants | 466 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 | 2 / 301 | 2 / 293 | 3 / 298 | 5 / 591 |
| other Total, other adverse events | 188 / 301 | 184 / 293 | 176 / 298 | 360 / 591 |
| serious Total, serious adverse events | 32 / 301 | 23 / 293 | 26 / 298 | 49 / 591 |
Outcome results
Primary
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 36
BCVA: Best-Corrected Visual Acuity; ETDRS: Early Treatment Diabetic Retinopathy Study; ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity)
Time frame: At Week 36
Population: Full analysis set (FAS): All participants randomly assigned to study intervention who were exposed to study intervention (active or sham injection) at least once.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q4 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 36 | 17.5 Letters | Standard Error 0.7 |
| Aflibercept 8q8/3 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 36 | 17.4 Letters | Standard Error 0.7 |
| Aflibercept 8q8/5 | Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 36 | 18.3 Letters | Standard Error 0.6 |
Comparison: 8q8/3 -2q4p-value: <0.000195% CI: [-2, 1.9]Mixed Models Analysis
Comparison: 8q8/5 -2q4p-value: <0.000195% CI: [-1.1, 2.7]Mixed Models Analysis
Secondary
Change From Baseline in Central Sub-field Thickness (CST) at Week 36
Time frame: From baseline to Week 36
Population: Full analysis set (FAS): All participants randomly assigned to study intervention who were exposed to study intervention (active or sham injection) at least once.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q4 | Change From Baseline in Central Sub-field Thickness (CST) at Week 36 | -370.8 μm | Standard Error 3.9 |
| Aflibercept 8q8/3 | Change From Baseline in Central Sub-field Thickness (CST) at Week 36 | -370.9 μm | Standard Error 3.1 |
| Aflibercept 8q8/5 | Change From Baseline in Central Sub-field Thickness (CST) at Week 36 | -369.5 μm | Standard Error 2.3 |
Comparison: 8q8/3 - 2q4p-value: 0.980495% CI: [-10, 9.8]Mixed Models Analysis
Comparison: 8q8/5 - 2q4p-value: 0.786395% CI: [-7.7, 10.2]Mixed Models Analysis
Secondary
Change From Baseline in NEI VFQ 25 Total Score at Week 36
NEI-VFQ-25: National Eye Institute Visual Functioning Questionnaire-25; The NEI VFQ-25 total score ranges from 0 to 100. A higher score means a better outcome (better patient-reported visual function).
Time frame: From baseline to Week 36
Population: Full analysis set (FAS): All participants randomly assigned to study intervention who were exposed to study intervention (active or sham injection) at least once.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q4 | Change From Baseline in NEI VFQ 25 Total Score at Week 36 | 6.27 Scores on a scale | Standard Error 0.67 |
| Aflibercept 8q8/3 | Change From Baseline in NEI VFQ 25 Total Score at Week 36 | 5.91 Scores on a scale | Standard Error 0.61 |
| Aflibercept 8q8/5 | Change From Baseline in NEI VFQ 25 Total Score at Week 36 | 6.92 Scores on a scale | Standard Error 0.63 |
Comparison: 8q8/3 - 2q4p-value: 0.686995% CI: [-2.1, 1.4]ANCOVA
Comparison: 8q8/5 - 2q495% CI: [-1.2, 2.45]ANCOVA
Secondary
Number of Active Injections From Baseline to Week 36
Active injections refer to the number of injections that were actually administered, as opposed to the number of planned injections.
Time frame: From baseline to Week 36
Population: Full analysis set (FAS): All participants randomly assigned to study intervention who were exposed to study intervention (active or sham injection) at least once.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept 2q4 | Number of Active Injections From Baseline to Week 36 | 8.8 Number of active injections | Standard Error 0 |
| Aflibercept 8q8/3 | Number of Active Injections From Baseline to Week 36 | 6.1 Number of active injections | Standard Error 0 |
| Aflibercept 8q8/5 | Number of Active Injections From Baseline to Week 36 | 6.9 Number of active injections | Standard Error 0 |
Comparison: 8q8/3 -2q4p-value: <0.000195% CI: [-2.8, -2.6]ANCOVA
Comparison: 8q8/5 -2q4p-value: <0.000195% CI: [-1.9, -1.7]ANCOVA
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36
TEAEs were defined as AEs that occurred in the time frame from first injection (active or sham) to the last injection (active or sham) plus 30 days. Ocular TEAEs in study eye and non-ocular TEAEs are included (ocular TEAEs in fellow eye are excluded)
Time frame: Through Week 36
Population: Safety analysis set (SAF): All participants randomly assigned to study intervention who were exposed to study intervention (active or sham injection) at least once. Analysis of the SAF was performed according to the treatment the participant actually received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aflibercept 2q4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TEAEs | 188 Participants |
| Aflibercept 2q4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TESAEs | 32 Participants |
| Aflibercept 8q8/3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TESAEs | 23 Participants |
| Aflibercept 8q8/3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TEAEs | 184 Participants |
| Aflibercept 8q8/5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TEAEs | 176 Participants |
| Aflibercept 8q8/5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TESAEs | 26 Participants |
| All Aflibercept HD | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TEAEs | 360 Participants |
| All Aflibercept HD | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36 | Number of participants with TESAEs | 49 Participants |
Secondary
Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 36
ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity)
Time frame: At Week 36
Population: Full analysis set (FAS): All participants randomly assigned and exposed to study intervention (active or sham injection) at least once.~The Overall Number of Participants Analyzed differs from the Overall Number of Baseline Participants because only observed cases were used, excluding data after an intercurrent event (ICE) (e.g., stopping intervention or using prohibited medication before Week 36). Missing cases were not included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept 2q4 | Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 36 | 179 Participants |
| Aflibercept 8q8/3 | Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 36 | 189 Participants |
| Aflibercept 8q8/5 | Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 36 | 189 Participants |
Secondary
Participants Dosed Only Q8 Through Week 36 in the 8 mg Q8 Group
Number of participants in the aflibercept 8q8/3 and the aflibercept 8q8/5 groups who were able to maintain every 8 weeks (Q8) dosing through Week 36. Only participants who did not discontinue study intervention prior to Week 36, and were therefore considered completers for Week 36, were included in the analysis of this endpoint.
Time frame: Through Week 36
Population: SAF: All participants randomly assigned to study intervention who were exposed to study intervention (active or sham injection) at least once. Analysis of the SAF was performed according to the treatment the participant actually received (as treated).~The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants because only participants considered as completers for Week 36 were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept 2q4 | Participants Dosed Only Q8 Through Week 36 in the 8 mg Q8 Group | 246 Participants |
| Aflibercept 8q8/3 | Participants Dosed Only Q8 Through Week 36 in the 8 mg Q8 Group | 255 Participants |
| Aflibercept 8q8/5 | Participants Dosed Only Q8 Through Week 36 in the 8 mg Q8 Group | 501 Participants |
Secondary
Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 36
Time frame: From baseline at Week 36
Population: Full analysis set (FAS): All participants randomly assigned and exposed to study intervention (active or sham injection) at least once.~The Overall Number of Participants Analyzed differs from the Overall Number of Baseline Participants because only observed cases were used, excluding data after an intercurrent event (ICE) (e.g., stopping intervention or using prohibited medication before Week 36). Missing cases were not included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept 2q4 | Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 36 | 158 Participants |
| Aflibercept 8q8/3 | Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 36 | 153 Participants |
| Aflibercept 8q8/5 | Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 36 | 161 Participants |
Secondary
Participants Having no Intraretinal Fluid (IRF) and no Sub-retinal Fluid (SRF) in the Center Subfield at Week 36
Number of participants with no retinal fluid (no IRF and no SRF) in the central subfield at Week 36
Time frame: At Week 36
Population: Full analysis set (FAS): All participants randomly assigned and exposed to study intervention (active or sham injection) at least once.~The Overall Number of Participants Analyzed differs from the Overall Number of Baseline Participants because only observed cases were used, excluding data after an intercurrent event (ICE) (e.g., stopping intervention or using prohibited medication before Week 36). Missing cases were not included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept 2q4 | Participants Having no Intraretinal Fluid (IRF) and no Sub-retinal Fluid (SRF) in the Center Subfield at Week 36 | 221 Participants |
| Aflibercept 8q8/3 | Participants Having no Intraretinal Fluid (IRF) and no Sub-retinal Fluid (SRF) in the Center Subfield at Week 36 | 211 Participants |
| Aflibercept 8q8/5 | Participants Having no Intraretinal Fluid (IRF) and no Sub-retinal Fluid (SRF) in the Center Subfield at Week 36 | 202 Participants |
Secondary
Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36
Total aflibercept is the sum of free and adjusted bound aflibercept.
Time frame: From baseline through Week 36
Population: Pharmacokinetic analysis set (PKS): All participants randomly assigned to study intervention with at least one non-missing PK result after the first dose of study intervention.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Aflibercept 2q4 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 4 | 91.6 ng/mL | Geometric Coefficient of Variation 55.82 |
| Aflibercept 2q4 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 24 | 165.6 ng/mL | Geometric Coefficient of Variation 58.72 |
| Aflibercept 2q4 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 16 | 241.6 ng/mL | Geometric Coefficient of Variation 48.4 |
| Aflibercept 2q4 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 36 | 167.8 ng/mL | Geometric Coefficient of Variation 58.81 |
| Aflibercept 2q4 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 12 | 151.5 ng/mL | Geometric Coefficient of Variation 56.99 |
| Aflibercept 8q8/3 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 36 | 366.0 ng/mL | Geometric Coefficient of Variation 57.87 |
| Aflibercept 8q8/3 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 4 | 281.8 ng/mL | Geometric Coefficient of Variation 52.16 |
| Aflibercept 8q8/3 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 12 | 451.7 ng/mL | Geometric Coefficient of Variation 58.83 |
| Aflibercept 8q8/3 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 16 | 470.5 ng/mL | Geometric Coefficient of Variation 58.24 |
| Aflibercept 8q8/3 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 24 | 179.8 ng/mL | Geometric Coefficient of Variation 73.07 |
| Aflibercept 8q8/5 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 12 | 452.6 ng/mL | Geometric Coefficient of Variation 57.04 |
| Aflibercept 8q8/5 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 36 | 313.8 ng/mL | Geometric Coefficient of Variation 97.3 |
| Aflibercept 8q8/5 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 24 | 202.5 ng/mL | Geometric Coefficient of Variation 80.94 |
| Aflibercept 8q8/5 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 4 | 270.7 ng/mL | Geometric Coefficient of Variation 63.78 |
| Aflibercept 8q8/5 | Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 | Week 16 | 729.0 ng/mL | Geometric Coefficient of Variation 43.82 |