Neovascular (Wet) Age-Related Macular Degeneration
Conditions
Brief summary
The primary objectives of the study are to determine the safety of high-dose aflibercept (hereafter referred to as HD) and to determine if HD provides greater intraocular pharmacodynamic (PD) effect and/or longer duration of action compared to intravitreal aflibercept injection (hereafter referred to as IAI).
Interventions
DRUGaflibercept
Intravitreally (IVT) administered as a liquid formulation in a vial
Intravitreally (IVT) administered as a liquid formulation in a vial
Sponsors
Bayer
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Single-masked: The patients, visual acuity examiners, imaging technicians and reading center will be masked to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Men or women ≥50 years of age with active subfoveal choroidal neovascularization (CNV) secondary to nAMD * Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 78 to 24 (Snellen equivalent of 20/32 to 20/320) in the study eye Key
Exclusion criteria
* Evidence of CNV due to any cause other than nAMD in either eye * Evidence of diabetic macular edema (DME) or diabetic retinopathy (defined as more than 1 microaneurysm) in either eye in diabetic patients * Prior use of IVT anti-VEGF agents (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) in the study eye * Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy) * Previous use of intraocular or periocular corticosteroids within 120 days of screening or treatment with an IVT steroid implant at any time in the study eye * History of vitreoretinal surgery (including scleral buckling) in the study eye * Any other intraocular surgery within 12 weeks (84 days) before the screening visit * History of corneal transplant or corneal dystrophy in study eye NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Up to Week 44 | — |
| Number of Participants With at Least One Serious TEAE | Up to Week 44 | — |
| Number of Participants Without Retinal Fluid in the Center Subfield of Study Eye | At Week 16 | Center subfield=the circular area in 1 millimeter (mm) diameter centered around the center point of the fovea. Without fluid defined as absence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the center subfield. Presence of retinal fluid was assessed by spectral domain optical coherence tomography (SD-OCT) |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Of the 245 participants screened, 106 participants were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Intravitreal Aflibercept Injection (IAI) Treatment-naïve participants with neovascular wet age-related macular degeneration (nAMD) were randomized in a 1:1 ratio to receive IAI (2 mg) monthly for 3 initial injections (baseline, week 4, and week 8), followed by additional doses at weeks 20 and 32. | 53 |
| High-Dose Aflibercept Injection (HD) Treatment-naïve participants with nAMD were randomized in a 1:1 ratio to receive HD aflibercept (8 mg) monthly for 3 initial injections (baseline, week 4, and week 8), followed by additional doses at weeks 20 and 32. | 53 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Intravitreal Aflibercept Injection (IAI) | High-Dose Aflibercept Injection (HD) | Total |
|---|---|---|---|
| Age, Continuous | 77.7 years STANDARD_DEVIATION 8.27 | 77.0 years STANDARD_DEVIATION 7.69 | 77.4 years STANDARD_DEVIATION 7.95 |
| Number of Participants without Retinal Fluid in the Center Subfield of Study Eye | 9 Participants | 10 Participants | 19 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic of Latino | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 49 Participants | 51 Participants | 100 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 51 Participants | 52 Participants | 103 Participants |
| Sex: Female, Male Female | 36 Participants | 30 Participants | 66 Participants |
| Sex: Female, Male Male | 17 Participants | 23 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 1 / 53 |
| other Total, other adverse events | 14 / 53 | 19 / 53 |
| serious Total, serious adverse events | 4 / 53 | 7 / 53 |
Outcome results
Primary
Number of Participants With at Least One Serious TEAE
Time frame: Up to Week 44
Population: SAF: All randomized participants who received any study drug; it was based on the treatment received (as treated)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intravitreal Aflibercept Injection (IAI) | Number of Participants With at Least One Serious TEAE | Participants with at least 1 Non-Ocular Serious TEAE | 4 Participants |
| Intravitreal Aflibercept Injection (IAI) | Number of Participants With at Least One Serious TEAE | Participants with at least 1 Ocular Serious TEAE of the Study Eye | 1 Participants |
| Intravitreal Aflibercept Injection (IAI) | Number of Participants With at Least One Serious TEAE | Participants with at least 1 Ocular Serious TEAE of the Fellow Eye | 0 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants With at Least One Serious TEAE | Participants with at least 1 Non-Ocular Serious TEAE | 5 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants With at Least One Serious TEAE | Participants with at least 1 Ocular Serious TEAE of the Study Eye | 2 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants With at Least One Serious TEAE | Participants with at least 1 Ocular Serious TEAE of the Fellow Eye | 0 Participants |
Primary
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: Up to Week 44
Population: Safety analysis set (SAF): All randomized participants who received any study drug; it was based on the treatment received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intravitreal Aflibercept Injection (IAI) | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Participants with at least 1 Ocular TEAE of the Study Eye | 20 Participants |
| Intravitreal Aflibercept Injection (IAI) | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Participants with at least 1 Ocular TEAE of the Fellow Eye | 13 Participants |
| Intravitreal Aflibercept Injection (IAI) | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Participants with at least 1 Non-Ocular TEAE | 24 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Participants with at least 1 Ocular TEAE of the Study Eye | 20 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Participants with at least 1 Ocular TEAE of the Fellow Eye | 13 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Participants with at least 1 Non-Ocular TEAE | 28 Participants |
Primary
Number of Participants Without Retinal Fluid in the Center Subfield of Study Eye
Center subfield=the circular area in 1 millimeter (mm) diameter centered around the center point of the fovea. Without fluid defined as absence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the center subfield. Presence of retinal fluid was assessed by spectral domain optical coherence tomography (SD-OCT)
Time frame: At Week 16
Population: Full analysis set (FAS): All randomized participants; it was based on the treatment allocated (as randomized). Missing post-baseline values for a given participant were imputed using the last observation carried forward (LOCF).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intravitreal Aflibercept Injection (IAI) | Number of Participants Without Retinal Fluid in the Center Subfield of Study Eye | 18 Participants |
| High-Dose Aflibercept Injection (HD) | Number of Participants Without Retinal Fluid in the Center Subfield of Study Eye | 27 Participants |