Macular Edema Secondary to Central Retinal Vein Occlusion
Conditions
Keywords
Macular edema, Retinal vein occlusion, CRVO, VEGF Trap-Eye, best-corrected visual acuity, Regeneron, COPERNICUS
Brief summary
This is a phase 3 study to determine the efficacy of VEGF Trap-Eye injected into the eye on vision function in subjects with macular edema as a consequence of central retinal vein occlusion.
Interventions
BIOLOGICALVEGF Trap-Eye 2.0mg
Monthly intravitreal injection out to the Week 24 Primary endpoint
DRUGSham
Monthly sham intravitreal injection out to Week 24 Primary Endpoint
Sponsors
Bayer
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects at least 18 years of age with center-involved macular edema secondary to CRVO with mean central retinal thickness ≥ 250 μm on OCT * ETDRS best corrected visual acuity of 20/40 to 20/320 (73 to 24 letters) in the study eye
Exclusion criteria
* Previous treatment with anti-angiogenic drugs in the study eye (Pegaptanib sodium,anecortave acetate, bevacizumab, ranibizumab, etc.) * Prior panretinal laser photocoagulation or macular laser photocoagulation in the study eye * CRVO disease duration \> 9 months from date of diagnosis * Previous use of intraocular corticosteroids in the study eye or use of periocular corticosteroids in the study eye within the 3 months prior to Day 1 * Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in either the study eye or fellow eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score | Baseline and at Week 24 | Percentage values indicate the number of subjects in each arm who were able to read an additional 15 letters or more at Week 24 compared to baseline. Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 letters (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF) | Baseline and at Week 24 | Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. |
| Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF | Baseline and at Week 24 | — |
| Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Baseline to Week 24 | — |
| Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF) | Baseline and at Week 24 | The NEI VFQ-25 assesses visual function and quality of life. Total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight. |
Countries
Canada, Colombia, India, Israel, United States
Participant flow
Recruitment details
The study was conducted at 55 study centers in the United States, Canada, Columbia, India, and Israel. The recruitment period occurred between 08 Jul 2009 and 29 Apr 2010.
Pre-assignment details
273 participants were screened, 189 randomized, and 188 were included in the Safety Analysis Set (SAF). The Full Analysis Set (FAS) included 187 participants with at least one post-baseline assessment.
Participants by arm
| Arm | Count |
|---|---|
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24. | 114 |
| Sham Treatment Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24. | 74 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Lack of Efficacy | 0 | 4 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Sham Treatment | Total | Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) |
|---|---|---|---|
| Age Continuous | 67.5 years STANDARD_DEVIATION 14.22 | 66.3 years STANDARD_DEVIATION 13.83 | 65.5 years STANDARD_DEVIATION 13.57 |
| Baseline Best Corrected Visual Acuity (BCVA) Letter Score | 48.7 letters correctly read STANDARD_DEVIATION 14.41 | 49.9 letters correctly read STANDARD_DEVIATION 14.1 | 50.7 letters correctly read STANDARD_DEVIATION 13.9 |
| Baseline Intraocular Pressure | 15.0 millimeters of mercury (mmHg) STANDARD_DEVIATION 2.83 | 15.1 millimeters of mercury (mmHg) STANDARD_DEVIATION 3.09 | 15.1 millimeters of mercury (mmHg) STANDARD_DEVIATION 3.26 |
| Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score | 78.01 scores on a scale STANDARD_DEVIATION 16.26 | 77.81 scores on a scale STANDARD_DEVIATION 16.04 | 77.67 scores on a scale STANDARD_DEVIATION 15.96 |
| Baseline Retinal Thickness by Optical Coherence Tomography (OCT) | 678.4 microns STANDARD_DEVIATION 248.66 | 668.1 microns STANDARD_DEVIATION 241.23 | 661.7 microns STANDARD_DEVIATION 237.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 30 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 158 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants with Retinal Perfusion at Baseline Indeterminate | 12 participants | 32 participants | 20 participants |
| Number of Participants with Retinal Perfusion at Baseline Non-Perfused | 12 participants | 29 participants | 17 participants |
| Number of Participants with Retinal Perfusion at Baseline Perfused | 50 participants | 127 participants | 77 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 18 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 60 Participants | 148 Participants | 88 Participants |
| Sex: Female, Male Female | 35 Participants | 80 Participants | 45 Participants |
| Sex: Female, Male Male | 39 Participants | 108 Participants | 69 Participants |
| Time Since Central Retinal Vein Occlusion (CRVO) Diagnosis </= 2 Months | 53 participants | 117 participants | 64 participants |
| Time Since Central Retinal Vein Occlusion (CRVO) Diagnosis > 2 Months | 21 participants | 70 participants | 49 participants |
| Time Since Central Retinal Vein Occlusion (CRVO) Diagnosis Missing | 0 participants | 1 participants | 1 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 | 57 / 114 | 34 / 74 | 76 / 110 | 50 / 60 |
| serious Total, serious adverse events | 6 / 114 | 6 / 74 | 20 / 110 | 14 / 60 |
Outcome results
Primary
Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score
Percentage values indicate the number of subjects in each arm who were able to read an additional 15 letters or more at Week 24 compared to baseline. Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 letters (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.
Time frame: Baseline and at Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score | 64 percentage of participants |
| Sham Treatment | Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score | 9 percentage of participants |
p-value: <0.000195% CI: [33, 56.6]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF)
Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.
Time frame: Baseline and at Week 24
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF) | 17.3 letters correctly read | Standard Deviation 12.78 |
| Sham Treatment | Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF) | -4.0 letters correctly read | Standard Deviation 17.96 |
p-value: <0.000195% CI: [17.36, 26.04]ANCOVA
ANCOVA
Secondary
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
Time frame: Baseline and at Week 24
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF | -457.2 microns | Standard Deviation 238.21 |
| Sham Treatment | Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF | -144.8 microns | Standard Deviation 291.07 |
p-value: <0.000195% CI: [-389.4, -234.4]ANCOVA
ANCOVA
Secondary
Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF)
The NEI VFQ-25 assesses visual function and quality of life. Total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.
Time frame: Baseline and at Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF) | 7.2 scores on a scale | Standard Deviation 12.11 |
| Sham Treatment | Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF) | 0.8 scores on a scale | Standard Deviation 9.79 |
p-value: 0.000995% CI: [2.61, 9.91]ANCOVA
ANCOVA
Secondary
Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks
Time frame: Baseline to Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Any neovascularization | 0 percentage of participants |
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Neovascularization of the optic disc (NVD) | 0 percentage of participants |
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Neovascularization elsewhere in the fundus (NVE) | 0 percentage of participants |
| Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Anterior segment neovascularization | 0 percentage of participants |
| Sham Treatment | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Neovascularization elsewhere in the fundus (NVE) | 0 percentage of participants |
| Sham Treatment | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Any neovascularization | 6.8 percentage of participants |
| Sham Treatment | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Anterior segment neovascularization | 6.8 percentage of participants |
| Sham Treatment | Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks | Neovascularization of the optic disc (NVD) | 0 percentage of participants |
p-value: 0.005995% CI: [-12.2, -1.1]Cochran-Mantel-Haenszel