Macular Degeneration
Conditions
Brief summary
This study will assess the efficacy and safety of intravitreally (IVT), i.e. directly into the eye administered VEGF Trap-Eye compared with photodynamic therapy (PDT) on visual function in Chinese subjects with age-related neovascular or wet age-related macular degeneration. Subjects will be randomized in a 3:1 ratio to either receive VEGF Trap-Eye or PDT. Both treatment groups will receive the other treatment as a sham procedure.
Detailed description
Adverse events collection will be covered in Adverse Events section.
Interventions
BIOLOGICALAflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Participants in the VEGF Trap-Eye group received intravitreal injections every 8 weeks following a loading phase with injections given every 4 weeks for an overall treatment period of 48 weeks. Additionally, sham PDT treatments was administered as needed.
DRUGVisudyne
Participants in the PDT group (Visudyne group) received Visudyne as needed. Additionally, sham IVT injections was administered until week 28. Thereafter, subjects in the PDT group received active (= no sham) VEGF Trap-Eye treatment until week 48.
Sponsors
Regeneron Pharmaceuticals
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent form * Men and women ≥ 50 years of age. * Active predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to wAMD (wet Age-Related Macular Degeneration) * BCVA (best corrected visual acuity) of 20/40 to 20/320 in the study eye
Exclusion criteria
* Only one functional eye * Presence of CNV with an origin other than wAMD * Any prior ocular or systemic treatment or surgery for wAMD, except dietary supplements or vitamins
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 28 - Last Observation Carried Forward (LOCF) | Baseline and at week 28 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Lost Fewer Than 15 Letters at Week 28 - LOCF | At week 28 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321) Participants received 2.0 mg intravitreal aflibercept injection (IAI) every 4 weeks for the first 12 weeks, followed by additional 2.0 mg IAI every 8 weeks until week 48. Additionally, sham photodynamic therapy (PDT) treatments was administered as needed. | 228 |
| PDT Treatments Participants received PDT as needed. Additionally, sham IAI injections was administered until week 28. Thereafter, participants received active IAI treatment until week 48. | 76 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 2 |
Baseline characteristics
| Characteristic | Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321) | PDT Treatments | Total |
|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 8.8 | 64.9 Years STANDARD_DEVIATION 8.5 | 65.1 Years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 86 Participants | 22 Participants | 108 Participants |
| Sex: Female, Male Male | 142 Participants | 54 Participants | 196 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 77 / 228 | 33 / 76 | 18 / 216 | 9 / 71 |
| serious Total, serious adverse events | 13 / 228 | 4 / 76 | 5 / 216 | 3 / 71 |
Outcome results
Primary
Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 28 - Last Observation Carried Forward (LOCF)
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
Time frame: Baseline and at week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321) | Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 28 - Last Observation Carried Forward (LOCF) | 14.0 Letters correctly read | Standard Deviation 12.1 |
| PDT Treatments | Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 28 - Last Observation Carried Forward (LOCF) | 3.9 Letters correctly read | Standard Deviation 14.6 |
Comparison: Null hypothesis: mean changes are identical in both groups. A sample size of 300 subjects with a 3:1 (EYLEA to PDT) randomization ratio is sufficient to detect the superiority of EYLEA to PDT assuming a two-sided alpha level of 0.05, a power of 90%, a treatment difference of 7.5 letters and a common standard deviation of 14 letters.p-value: <0.000195% CI: [6.8, 13.4]ANCOVA
Secondary
Percentage of Participants Who Lost Fewer Than 15 Letters at Week 28 - LOCF
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
Time frame: At week 28
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321) | Percentage of Participants Who Lost Fewer Than 15 Letters at Week 28 - LOCF | 98.7 Percentage of participants |
| PDT Treatments | Percentage of Participants Who Lost Fewer Than 15 Letters at Week 28 - LOCF | 92.1 Percentage of participants |
Comparison: Null hypothesis: proportions are identical in both groupsp-value: 0.035995% CI: [0.4, 12.9]Cochran-Mantel-Haenszel