Macular Degeneration
Conditions
Keywords
Age-related macular degeneration (AMD), Eylea treatment, Treat and Extend, Intravitreal
Brief summary
To compare the efficacy of 2 mg aflibercept administered by two different intravitreal (IVT) treatment regimens to subjects with neovascular age-related macular degeneration (nAMD)
Detailed description
330 Patients who have completed at least one year of treatment with aflibercept will be randomized to two different aflibercept regimens and followed for 76 weeks.
Interventions
DRUGAflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
A dose of 2 mg aflibercept injected intravitreally
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
51 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The following criteria must have been met at the initial start of aflibercept treatment (i.e. start of aflibercept treatment at least 1 year before this study): * Subject had primary subfoveal choroidal neovascularization (CNV) lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea, as evidenced by fluorescein angiography/photography (FA/FP) of the study eye within 3 weeks before the initiation of aflibercept treatment. * The area of CNV occupied at least 50% of the total lesion within 3 weeks before the initiation of aflibercept treatment. * Documented best-corrected visual acuity (BCVA) was 20/40 to 20/320 (letter score of 73 to 25) in the study eye at the initiation of treatment. * Men and women \>= 51 years of age * The subject's history of aflibercept treatment meets ALL of the following: * Treatment in the study eye was initiated with three monthly (-1 week/+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed * Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks
Exclusion criteria
\- Any prior or concomitant therapy with an investigational or approved agent to treat neovascular AMD in the study eye other than aflibercept. * Total lesion size \> 12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by fluorescein angiography (FA) in the study eye * Subretinal hemorrhage that was: 1. 50% or more of the total lesion area, or 2. if the blood was under the fovea, and 3. the blood under the fovea was 1 or more disc areas in size in the study eye. * Scar or fibrosis making up more than 50% of the total lesion in the study eye. * Scar, fibrosis, or atrophy involving the center of the fovea in the study eye. * Presence of retinal pigment epithelial tears or rips involving the macula in the study eye. * Causes of CNV other than AMD in the study eye.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye | From baseline to Week 52 | Visual function was assessed with the procedure from the ETDRS adapted for the Age Related Eye Disease Study using charts with 70 letters at a starting distance of 4 meters. Charts are organized in 14 lines of decreasing size with 5 letters each. Participants reading up to 19 letters at 4 meters were tested at 1 meter to read the first 6 lines. The score equals the sum of letters read at 1 meter and 4 meters. If more than 19 letters are read at 4 meters the score equals the number of letters read plus 30. The score range is 0 to 100, and a higher score represents better visual function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye | At week 52 | — |
| Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | From baseline to week 52 | Retinal characteristic was evaluated using Optical coherence tomography (OCT). |
| Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye | From baseline to week 52 | Choroidal neovascularization measured by optical coherence tomography (OCT). |
| Percentage of Participants Maintaining Vision in the Study Eye | At week 52 | A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline. |
| Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire | From baseline to week 52 | National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) total score ranges from 0 to 100, where 100 represents the best possible score and 0 represents the worst. |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | Started after the first application of aflibercept in the study and less than or equal to 30 days after the last dose of study drug over approximately 1.5 years | — |
| Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye | At week 52 | — |
Countries
Austria, Canada, Czechia, France, Germany, Hungary, Italy, Lithuania, Poland, Portugal, Slovakia, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
Study was conducted at 76 centers in 14 countries or regions, between 29-SEP-2015 (first participant first visit) and 04-JUN-2020 (last participant last visit)
Pre-assignment details
At baseline, 336 participants were randomized to one of 2 treatment groups; 168 participants were randomized to the extended-dosing group and 168 participants were randomized to the 2Q8 (2 mg aflibercept administered every 8 weeks) group.
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept Extended Dosing Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed). | 167 |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed. | 168 |
| Total | 335 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other reason | 4 | 2 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Treatment failure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Total | Aflibercept Extended Dosing | Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) |
|---|---|---|---|
| Age, Continuous | 75.5 years STANDARD_DEVIATION 7.7 | 76.3 years STANDARD_DEVIATION 8.3 | 74.7 years STANDARD_DEVIATION 7 |
| Central retinal thickness (CRT) in the study eye | 260.9 μm STANDARD_DEVIATION 63.8 | 257.3 μm STANDARD_DEVIATION 67.8 | 264.4 μm STANDARD_DEVIATION 59.7 |
| Choroidal neovascularization (CNV) area in the study eye | 4.875 mm*2 STANDARD_DEVIATION 4.07 | 4.695 mm*2 STANDARD_DEVIATION 4.043 | 5.060 mm*2 STANDARD_DEVIATION 4.105 |
| Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual | 69.6 Letters read correctly STANDARD_DEVIATION 11.5 | 69.0 Letters read correctly STANDARD_DEVIATION 12.1 | 70.1 Letters read correctly STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 264 Participants | 136 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 71 Participants | 31 Participants | 40 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 64 Participants | 28 Participants | 36 Participants |
| Race (NIH/OMB) White | 271 Participants | 139 Participants | 132 Participants |
| Sex: Female, Male Female | 215 Participants | 107 Participants | 108 Participants |
| Sex: Female, Male Male | 120 Participants | 60 Participants | 60 Participants |
| Total score for National Eye Institute 25-Item Visual Function | 74.340 Score on a scale STANDARD_DEVIATION 17.034 | 72.889 Score on a scale STANDARD_DEVIATION 18.414 | 75.757 Score on a scale STANDARD_DEVIATION 15.495 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 167 | 3 / 168 |
| other Total, other adverse events | 60 / 167 | 70 / 168 |
| serious Total, serious adverse events | 26 / 167 | 23 / 168 |
Outcome results
Primary
Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye
Visual function was assessed with the procedure from the ETDRS adapted for the Age Related Eye Disease Study using charts with 70 letters at a starting distance of 4 meters. Charts are organized in 14 lines of decreasing size with 5 letters each. Participants reading up to 19 letters at 4 meters were tested at 1 meter to read the first 6 lines. The score equals the sum of letters read at 1 meter and 4 meters. If more than 19 letters are read at 4 meters the score equals the number of letters read plus 30. The score range is 0 to 100, and a higher score represents better visual function.
Time frame: From baseline to Week 52
Population: The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Extended Dosing | Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye | -0.3 Letters read correctly | Standard Deviation 7.5 |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye | -0.5 Letters read correctly | Standard Deviation 8.4 |
p-value: <0.000195% CI: [-1.51, 1.96]ANCOVA
Secondary
Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
Retinal characteristic was evaluated using Optical coherence tomography (OCT).
Time frame: From baseline to week 52
Population: The outcome measure was analyzed based on full analysis set (FAS) with number of participants evaluable for this specific end point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Extended Dosing | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | -24.4 μm | Standard Deviation 55.2 |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | -33.4 μm | Standard Deviation 47.1 |
Secondary
Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye
Choroidal neovascularization measured by optical coherence tomography (OCT).
Time frame: From baseline to week 52
Population: The outcome measure was analyzed based on full analysis set (FAS) with number of participants evaluable for this specific end point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Extended Dosing | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye | 0.274 mm*2 | Standard Deviation 2.723 |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye | 0.204 mm*2 | Standard Deviation 2.813 |
Secondary
Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire
National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) total score ranges from 0 to 100, where 100 represents the best possible score and 0 represents the worst.
Time frame: From baseline to week 52
Population: The outcome measure was analyzed based on full analysis set (FAS) with number of participants evaluable for this specific end point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Extended Dosing | Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire | 0.186 Score on a scale | Standard Deviation 9.601 |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire | -1.694 Score on a scale | Standard Deviation 10.328 |
95% CI: [-4.152, 0.392]
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time frame: Started after the first application of aflibercept in the study and less than or equal to 30 days after the last dose of study drug over approximately 1.5 years
Population: Number of participants with TEAE was analyzed based on safety analysis set (SAF) with number of participants evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aflibercept Extended Dosing | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 130 Participants |
| Aflibercept Extended Dosing | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 26 Participants |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 124 Participants |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 23 Participants |
Secondary
Percentage of Participants Maintaining Vision in the Study Eye
A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline.
Time frame: At week 52
Population: The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Extended Dosing | Percentage of Participants Maintaining Vision in the Study Eye | 95.2 Percentage of participants |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Percentage of Participants Maintaining Vision in the Study Eye | 94.0 Percentage of participants |
95% CI: [-3.7, 6]
Secondary
Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye
Time frame: At week 52
Population: The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Extended Dosing | Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye | 24.2 Percentage of participants |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye | 21.0 Percentage of participants |
Secondary
Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye
Time frame: At week 52
Population: The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Extended Dosing | Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye | 0 Percentage of participants |
| Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks) | Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye | 0.6 Percentage of participants |