Neovascular Age-related Macular Degeneration
Conditions
Keywords
Eyes, Neovascular, Macular Degeneration, Retina, AMD, VEGF Trap-Eye, Best Corrected Visual Acuity
Brief summary
The primary objective is to assess long-term safety and tolerability of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) in patients with neovascular AMD.
Detailed description
The dose evaluated in this study, Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg, will be the higher of the 2 dose strengths evaluated in parent study VGFT-OD-0605 (NCT00509795) and is the dose level administered in study VGFT-OD-0702 (NCT00527423), a long-term open-label extension study. For these reasons, this dose has been selected for this extension study. Participants will be seen in the clinic for quarterly visits starting with day 1 to assess safety. Study drug will be administered on an as-needed basis at the discretion of the investigator with a minimum allowed interval of every 4 weeks and a maximum allowed interval of every 12 weeks. This study will assess the frequency that re-treatment is needed and the effect of continued Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) treatment on BCVA.
Interventions
Sponsors
Bayer
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participation in Study VGFT-OD-0605 through week 96. * In the opinion of the investigator, the study eye has neovascular AMD and may continue to require treatment.
Exclusion criteria
* Presence of any condition that would jeopardize the patient's participation in this study. * Females who are pregnant, breastfeeding, or of childbearing potential, unwilling to practice adequate contraception throughout the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Baseline (day 1) through end of treatment (Week 180) | The primary endpoint in the study is the safety and tolerability of Intravitreal Aflibercept Injection in patients with neovascular AMD (Age-related Macular Degeneration) from day 1 through the end of treatment visit (week 180) based on the number of participants who experienced any treatment-emergent adverse event (TEAE). Treatment-emergent adverse events were categorized according to Ocular TEAEs in the study eye, Ocular TEAEs in the fellow eye, and Non-Ocular TEAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in BCVA Letter Score (mLOCF) | Baseline through Week 116 | The secondary endpoint in the study is the change in BCVA letter score from baseline through Week 116. (mLOCF: The last non-missing observation prior to the missing visit was carried forward to impute the missing data; no imputation after last visit; no baseline value carried forward). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Summary of Treatment Duration (Weeks) | Baseline through end of treatment (Week 180) | Treatment Duration = (last dose date - first dose date + 28)/7 |
| Summary of Study Duration (Weeks) | Baseline through end of treatment (Week 180) | Study Duration = (last visit/ discontinuation date - first dose date + 28)/7 |
Countries
Canada, United States
Participant flow
Recruitment details
After informed consent was obtained, the 323 participants who completed the parent study, VGFT-OD-0605 (NCT00509795), and met the protocol eligibility criteria, were enrolled at 71 clinical sites in the US & Canada. The first visit occurred concurrently with the last visit in the parent study. The last participant entered this study on 18-May-2011.
Pre-assignment details
Intravitreal Aflibercept Injection \[commercially known EYLEA® (aflibercept) Injection\] was approved in the US for treatment of neovascular (wet) age-related macular degeneration (AMD) as the study was ongoing. For collection of long-term safety and best corrected visual acuity data on EYLEA®, the study was extended in the US from 30 to 45 months.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Intravitreal Aflibercept Injection Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above. | 323 |
| Total | 323 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Death | 14 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Other | 23 |
| Overall Study | Termination of Study by Sponsor | 169 |
| Overall Study | Unwilling to sign ICF for amendment 4 | 3 |
| Overall Study | Withdrawal by Subject | 79 |
Baseline characteristics
| Characteristic | Open-label Intravitreal Aflibercept Injection |
|---|---|
| Age, Continuous | 79 years STANDARD_DEVIATION 7.83 |
| Sex: Female, Male Female | 196 Participants |
| Sex: Female, Male Male | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 102 / 323 |
| serious Total, serious adverse events | 105 / 323 |
Outcome results
Primary
Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD
The primary endpoint in the study is the safety and tolerability of Intravitreal Aflibercept Injection in patients with neovascular AMD (Age-related Macular Degeneration) from day 1 through the end of treatment visit (week 180) based on the number of participants who experienced any treatment-emergent adverse event (TEAE). Treatment-emergent adverse events were categorized according to Ocular TEAEs in the study eye, Ocular TEAEs in the fellow eye, and Non-Ocular TEAEs
Time frame: Baseline (day 1) through end of treatment (Week 180)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Number of participants with any TEAE | 290 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Any ocular TEAE | 239 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Any ocular TEAE: Study eye | 204 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Any ocular TEAE: Fellow eye | 169 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Any non-ocular TEAE | 232 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Any serious TEAE | 105 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Discontinuation of study due to AE | 12 participants |
| Open-label Intravitreal Aflibercept Injection | Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD | Any Death due to TEAE | 17 participants |
Secondary
Change in BCVA Letter Score (mLOCF)
The secondary endpoint in the study is the change in BCVA letter score from baseline through Week 116. (mLOCF: The last non-missing observation prior to the missing visit was carried forward to impute the missing data; no imputation after last visit; no baseline value carried forward).
Time frame: Baseline through Week 116
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Intravitreal Aflibercept Injection | Change in BCVA Letter Score (mLOCF) | -2.7 letters correctly read | Standard Deviation 12.5 |
Other Pre-specified
Summary of Study Duration (Weeks)
Study Duration = (last visit/ discontinuation date - first dose date + 28)/7
Time frame: Baseline through end of treatment (Week 180)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Intravitreal Aflibercept Injection | Summary of Study Duration (Weeks) | 116.9 weeks | Standard Deviation 44.3 |
Other Pre-specified
Summary of Treatment Duration (Weeks)
Treatment Duration = (last dose date - first dose date + 28)/7
Time frame: Baseline through end of treatment (Week 180)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Intravitreal Aflibercept Injection | Summary of Treatment Duration (Weeks) | 110.4 weeks | Standard Deviation 42.16 |