Wet Macular Degeneration
Conditions
Keywords
Eylea,, Aflibercept, Treat and Extend regimen, Age-related macular degeneration
Brief summary
To assess the efficacy of intravitreal (IVT) administration of aflibercept with two different approaches of Treat and Extend dosing regimens in Japanese subjects with neovascular (wet) Age-related Macular Degeneration (wAMD) . To assess the safety of IVT administration of aflibercept with two different approaches of Treat and Extend dosing regimen in Japanese subjects with wAMD for up to 2 years.
Interventions
DRUGAflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Aflibercept 2mg is intravitreally injected.
Sponsors
Regeneron Pharmaceuticals
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Japanese men and women ≥ 50 years of age * Active primary subfoveal choroidal neovascularization (CNV) lesions secondary to wAMD, including juxta-foveal lesions that affect the fovea as evidenced by fluorescein angiography (FA) in the study eye * Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) of 73 to 25 letters (approximately 20/40 to 20/320 at Snellen equivalent) in the study eye
Exclusion criteria
* Prior treatment of the study eye with intraocular anti-VEGF(Vascular Endothelial Growth Factor) agents, verteporfin photodynamic therapy (PDT), other laser, intraocular corticosteroids, surgical interventions (except cataract surgery more than 30 days prior to screening) or systemic use of anti-VEGF products within 3 months prior to study entry * Active or suspected infection in or surrounding of the study eye * Active severe intraocular inflammation in the study eye * Intraocular pressure (IOP) ≥ 25 mmHg in the study eye * Ocular condition in the study eye which may impact vision and confound study outcomes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in BCVA at Week 52 | Baseline and Week 52 | Visual functions of the study eye (at every visit) and the fellow eye were assessed, according to the ETDRS protocol as described in detail in the operation manual. A higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained Vision at Week 52 | 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. |
| Percentage of Participants Who Gained at Least 15 Letters of Vision Compared to Baseline at Week 52 | Baseline and Week 52 | — |
| Mean Change in Central Retinal Thickness (CRT) From Baseline at Week 52 | Baseline and week 52 | — |
| Percentage of Participants Without Fluid on Optical Coherence Tomography (OCT) at Week 52 | Week 52 | A participant was classified as without fluid if Evidence of new or persistent fluid on OCT was No. |
Countries
Japan
Participant flow
Recruitment details
Study was conducted in Japan between 19 December 2014 (first participant first visit) and 08 November 2017 (last participant last visit).
Pre-assignment details
288 participants were enrolled and 255 entered run-in phase. 8 were randomization failures. 247 participants were randomized (2 Weeks \[2W\] adjustment group: 124; 4 Weeks \[4W\] adjustment group: 123) at Week 16. All 247 participant:s were treated and 227 participants (111 in the 2W adjustment, 116 in the 4W adjustment) completed Week 52 treatment.
Participants by arm
| Arm | Count |
|---|---|
| 2 Weeks Adjustment Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96. | 124 |
| 4 Weeks Adjustment Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96. | 123 |
| Randomization Failure Participants entered run-in phase but discontinued the study before randomization after receiving at least one injection. | 7 |
| Total | 254 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 0 |
| Overall Study | Death | 2 | 1 | 0 |
| Overall Study | Logistical difficulties | 1 | 3 | 0 |
| Overall Study | Physician Decision | 2 | 1 | 0 |
| Overall Study | Progressive disease | 4 | 4 | 0 |
| Overall Study | Protocol Violation | 0 | 3 | 0 |
| Overall Study | Randomized failure | 0 | 0 | 8 |
| Overall Study | Required procedure failed | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 0 |
Baseline characteristics
| Characteristic | 2 Weeks Adjustment | 4 Weeks Adjustment | Randomization Failure | Total |
|---|---|---|---|---|
| Age, Continuous | 73.0 years STANDARD_DEVIATION 7.9 | 75.0 years STANDARD_DEVIATION 8.1 | 80.3 years STANDARD_DEVIATION 7.8 | 74.2 years STANDARD_DEVIATION 8.1 |
| Best-corrected visual acuity (BCVA) | 54.6 letters STANDARD_DEVIATION 13.1 | 55.3 letters STANDARD_DEVIATION 12 | 54.9 letters STANDARD_DEVIATION 17.9 | 55.0 letters STANDARD_DEVIATION 12.7 |
| Central Retinal Thickness | 386.5 μm STANDARD_DEVIATION 158.6 | 370.3 μm STANDARD_DEVIATION 120 | 371.6 μm STANDARD_DEVIATION 88.5 | 378.3 μm STANDARD_DEVIATION 139.4 |
| Choroidal neovascularization Classic CNV | 35 Participants | 42 Participants | 1 Participants | 78 Participants |
| Choroidal neovascularization Classic & Occult | 15 Participants | 17 Participants | 2 Participants | 34 Participants |
| Choroidal neovascularization No CNV | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Choroidal neovascularization Occult | 72 Participants | 62 Participants | 4 Participants | 138 Participants |
| Choroidal neovascularization Unknown | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Polypoidal Choroidal Vasculopathy Missing | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Polypoidal Choroidal Vasculopathy No | 76 Participants | 79 Participants | 5 Participants | 160 Participants |
| Polypoidal Choroidal Vasculopathy Yes | 46 Participants | 44 Participants | 2 Participants | 92 Participants |
| Retinal Angiomatous Proliferation Missing | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Retinal Angiomatous Proliferation No | 118 Participants | 114 Participants | 6 Participants | 238 Participants |
| Retinal Angiomatous Proliferation Yes | 4 Participants | 9 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Female | 36 Participants | 32 Participants | 1 Participants | 69 Participants |
| Sex: Female, Male Male | 88 Participants | 91 Participants | 6 Participants | 185 Participants |
| Typical age-related macular degeneration Missing | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Typical age-related macular degeneration No | 46 Participants | 48 Participants | 2 Participants | 96 Participants |
| Typical age-related macular degeneration Yes | 76 Participants | 75 Participants | 5 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 49 / 124 | 61 / 123 | 4 / 7 |
| serious Total, serious adverse events | 19 / 124 | 20 / 123 | 3 / 7 |
Outcome results
Primary
Mean Change From Baseline in BCVA at Week 52
Visual functions of the study eye (at every visit) and the fellow eye were assessed, according to the ETDRS protocol as described in detail in the operation manual. A higher score represents better functioning.
Time frame: Baseline and Week 52
Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 Weeks Adjustment | Mean Change From Baseline in BCVA at Week 52 | 9.0 letters | Standard Deviation 14.6 |
| 4 Weeks Adjustment | Mean Change From Baseline in BCVA at Week 52 | 8.4 letters | Standard Deviation 13.4 |
95% CI: [-3.8, 3]
Secondary
Mean Change in Central Retinal Thickness (CRT) From Baseline at Week 52
Time frame: Baseline and week 52
Population: The outcome measure is analyzed based on full analysis set (FAS) with number of subjects evaluable for this specific end point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 2 Weeks Adjustment | Mean Change in Central Retinal Thickness (CRT) From Baseline at Week 52 | -134.4 μm |
| 4 Weeks Adjustment | Mean Change in Central Retinal Thickness (CRT) From Baseline at Week 52 | -126.1 μm |
95% CI: [-24.3, 12.7]
Secondary
Percentage of Participants Who Gained at Least 15 Letters of Vision Compared to Baseline at Week 52
Time frame: Baseline and Week 52
Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Weeks Adjustment | Percentage of Participants Who Gained at Least 15 Letters of Vision Compared to Baseline at Week 52 | 32.5 percentage of participants |
| 4 Weeks Adjustment | Percentage of Participants Who Gained at Least 15 Letters of Vision Compared to Baseline at Week 52 | 30.9 percentage of participants |
95% CI: [-12.7, 9.8]
Secondary
Percentage of Participants Who Maintained Vision 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.
Time frame: Week 52
Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Weeks Adjustment | Percentage of Participants Who Maintained Vision at Week 52 | 96.7 percentage of participants |
| 4 Weeks Adjustment | Percentage of Participants Who Maintained Vision at Week 52 | 95.9 percentage of participants |
95% CI: [-5.7, 4]
Secondary
Percentage of Participants Without Fluid on Optical Coherence Tomography (OCT) at Week 52
A participant was classified as without fluid if Evidence of new or persistent fluid on OCT was No.
Time frame: Week 52
Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Weeks Adjustment | Percentage of Participants Without Fluid on Optical Coherence Tomography (OCT) at Week 52 | 68.3 Percentage of participants |
| 4 Weeks Adjustment | Percentage of Participants Without Fluid on Optical Coherence Tomography (OCT) at Week 52 | 69.1 Percentage of participants |
95% CI: [-10.6, 12.7]