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CompletedNCT00943072Updated May 27, 2013Results posted

Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central Retinal Vein Occlusion (CRVO)

A Phase 3 interventional study of VEGF Trap-Eye 2.0mg and Sham in Macular Edema Secondary to Central Retinal Vein Occlusion, sponsored by Regeneron Pharmaceuticals. Completed at 61 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-05-27.

Sponsored by Regeneron Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
189
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Macular Edema Secondary to Central Retinal Vein Occlusion

Keywords

  • Macular edema
  • Retinal vein occlusion
  • CRVO
  • VEGF Trap-Eye
  • best-corrected visual acuity
  • Regeneron
  • COPERNICUS
03

In context

Neoplasm Metastasis

3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.

This study's enrollment of 189 is above the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.

Browse Neoplasm Metastasis studies →

Lead sponsor

Regeneron Pharmaceuticals is the lead sponsor of 400 studies on the registry; 91 are open to participants now.

Of its 120 completed or terminated interventional studies of FDA-regulated products, 77 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
189 participants (actual)

Study arms

  • Experimental
    VEGF Trap-Eye

    Monthly IVT injection of VEGF Trap-Eye 2.0 mg until Week 24 Primary Endpoint

    Biological: VEGF Trap-Eye 2.0mg

  • Sham comparator
    Sham

    Monthly Sham IVT injection until Week 24 Primary Endpoint

    Drug: Sham

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

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF

    Time frame: Baseline and at Week 24

  3. 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

  4. 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

07

Results

Posted May 27, 2013

Participant flow

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.

Participant flow — Overall Study
MilestoneIntravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham Treatment
Started11574
Participants received treatment11474
Full analysis set (fas) population11473
Completed11060
Not completed514
Withdrew: Adverse event03
Withdrew: Death02
Withdrew: Withdrawal by subject31
Withdrew: Protocol violation01
Withdrew: Lost to follow-up12
Withdrew: Lack of efficacy04
Withdrew: Other11

Outcome measures

PrimaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score
percentage of participantsIntravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham Treatment
Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score649
Statistical analysis
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · Cochran-Mantel-Haenszel · p = < 0.0001 (P-value for the primary endpoint was calculated using 2-sided Cochran-Mantel-Haenszel test adjusted by regions (North America vs. Rest of World) and baseline BCVA (BCVA \> 20/200 and BCVA ≤ 20/200)) · Risk difference (rd): 44.8 · 95% CI 33.0 to 56.6The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
SecondaryChange 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
Reported as:
Mean · letters correctly read
Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF)
letters correctly readIntravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham Treatment
Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF)17.3 ± 12.78-4.0 ± 17.96
Statistical analysis
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · ANCOVA · p = < 0.0001 · Risk difference (rd): 21.70 · 95% CI 17.36 to 26.04RD is the IAI group minus sham group. 95% confidence interval is for the RD.
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · ANCOVA · Least square mean: 16.36LS Mean indicates is the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
SecondaryChange From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
Time frame:
Baseline and at Week 24
Reported as:
Mean · microns
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
micronsIntravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham Treatment
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF-457.2 ± 238.21-144.8 ± 291.07
Statistical analysis
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · ANCOVA · p = < 0.0001 · Risk difference (rd): -311.9 · 95% CI -389.4 to -234.4The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group. 95% confidence interval is for the RD.
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · ANCOVA · Least square mean: -487.1The Least Square Mean indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
SecondaryPercentage 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
Reported as:
Number · percentage of participants
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
percentage of participantsIntravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham Treatment
Any neovascularization06.8
Anterior segment neovascularization06.8
Neovascularization of the optic disc (NVD)00
Neovascularization elsewhere in the fundus (NVE)00
Statistical analysis
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · Cochran-Mantel-Haenszel · p = 0.0059 · Risk difference (rd): -6.6 · 95% CI -12.2 to -1.1The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group. 95% confidence interval is for the RD.
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF)
scores on a scaleIntravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham Treatment
Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF)7.2 ± 12.110.8 ± 9.79
Statistical analysis
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · ANCOVA · p = 0.0009 · Risk difference (rd): 6.26 · 95% CI 2.61 to 9.91The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group. 95% confidence interval is for the RD.
  • Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) vs Sham Treatment · ANCOVA · Least square mean: 8.80Least Square Mean indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.

Adverse events

Collected over Baseline to Week 24; Week 24 to Week 100. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intravitreal Aflibercept Injection (IAI) (Baseline to Week 24)—6/114 (5.3%)57/114 (50%)
Sham Treatment (Baseline to Week 24)—6/74 (8.1%)34/74 (45.9%)
IAI to IAI (Week 24 to Week 100)—20/110 (18.2%)76/110 (69.1%)
Sham Treatment to IAI (Week 24 to Week 100)—14/60 (23.3%)50/60 (83.3%)
Most frequent serious events
Showing 10 of 124
Most frequent serious events
EventIntravitreal Aflibercept Injection (IAI) (Baseline to Week 24)Sham Treatment (Baseline to Week 24)IAI to IAI (Week 24 to Week 100)Sham Treatment to IAI (Week 24 to Week 100)
PneumoniaInfections and infestations0/1141/740/1103/60
Renal failure acuteRenal and urinary disorders0/1140/741/1102/60
GlaucomaEye disorders0/1142/740/1101/60
Iris neovascularisationEye disorders0/1142/740/1100/60
Cystoid macular oedemaEye disorders0/1140/742/1100/60
Inguinal herniaGastrointestinal disorders0/1140/742/1100/60
Coronary artery stenosisCardiac disorders0/1140/742/1100/60
Urinary tract infectionInfections and infestations0/1140/742/1100/60
AnaemiaBlood and lymphatic system disorders1/1140/740/1101/60
NeutropeniaBlood and lymphatic system disorders0/1140/740/1101/60
Most frequent other events
Showing 10 of 25
Most frequent other events
EventIntravitreal Aflibercept Injection (IAI) (Baseline to Week 24)Sham Treatment (Baseline to Week 24)IAI to IAI (Week 24 to Week 100)Sham Treatment to IAI (Week 24 to Week 100)
Visual acuity reducedEye disorders7/11412/7427/1108/60
Retinal pigment epitheliopathyEye disorders0/1140/740/11012/60
Macular oedemaEye disorders0/1140/7420/1100/60
HypertensionVascular disorders10/1144/7413/1109/60
Eye painEye disorders16/1144/749/1104/60
Cystoid macular oedemaEye disorders0/1140/7414/1104/60
MaculopathyEye disorders10/1140/746/1100/60
Optic disc vascular disorderEye disorders8/1140/746/1105/60
Retinal exudatesEye disorders7/1140/740/1105/60
Protein urine presentInvestigations0/1140/740/1105/60

Baseline characteristics

Age Continuous
Age Continuous(years)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Mean65.5 ± 13.5767.5 ± 14.2266.3 ± 13.83
Sex: Female, Male
Sex: Female, Male(Participants)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Female453580
Male6939108
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Hispanic or Latino181230
Not Hispanic or Latino9662158
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
American Indian or Alaska Native202
Asian729
Native Hawaiian or Other Pacific Islander011
Black or African American5510
White8860148
More than one race12618
Unknown or Not Reported000
Baseline Retinal Thickness by Optical Coherence Tomography (OCT)
Baseline Retinal Thickness by Optical Coherence Tomography (OCT)(microns)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Mean661.7 ± 237.37678.4 ± 248.66668.1 ± 241.23
Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score
Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score(scores on a scale)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Mean77.67 ± 15.9678.01 ± 16.2677.81 ± 16.04
Baseline Intraocular Pressure
Baseline Intraocular Pressure(millimeters of mercury (mmHg))Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Mean15.1 ± 3.2615.0 ± 2.8315.1 ± 3.09
Number of Participants with Retinal Perfusion at Baseline
Number of Participants with Retinal Perfusion at Baseline(participants)Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)Sham TreatmentTotal
Perfused7750127
Non-Perfused171229
Indeterminate201232

2 further baseline measures are reported on the registry.

08

Study locations

61 sites
  • Phoenix, Arizona 85014, United States
  • Phoenix, Arizona 85020, United States
  • Tucson, Arizona 85704, United States
  • Arcadia, California 91007, United States
  • Beverly Hills, California 90211, United States
  • La Jolla, California 92037, United States
  • Mountain View, California 94040, United States
  • Oakland, California 94609, United States
  • Sacramento, California 95841, United States
  • Torrance, California 90503, United States
  • New London, Connecticut 06320, United States
  • Altamonte Springs, Florida 32701, United States
  • Fort Lauderdale, Florida 33334, United States
  • Fort Myers, Florida 33907, United States
  • Fort Myers, Florida 33912, United States
  • Miami, Florida 33143, United States
  • Palm Beach Gardens, Florida 33410, United States
  • Winter Haven, Florida 33880, United States
  • Augusta, Georgia 30909, United States
  • Chicago, Illinois 60612, United States
  • Wichita, Kansas 67214, United States
  • Baltimore, Maryland 21209, United States
  • Hagerstown, Maryland 21740, United States
  • Towson, Maryland 21204, United States
  • Boston, Massachusetts 02114, United States
  • Grand Rapids, Michigan 49525, United States
  • Jackson, Michigan 48104, United States
  • Lincoln, Nebraska 68506, United States
  • Las Vegas, Nevada 89135, United States
  • Northfield, New Jersey 08225, United States
  • Toms River, New Jersey 08755, United States
  • Rochester, New York 14620, United States
  • Winston-Salem, North Carolina 27157, United States
  • Cleveland, Ohio 44195, United States
  • Oklahoma City, Oklahoma 73104, United States
  • Portland, Oregon 97210, United States
  • Salem, Oregon 97302, United States
  • Kingston, Pennsylvania 18704, United States
  • Pittsburgh, Pennsylvania 15213, United States
  • West Columbia, South Carolina 29169, United States
  • Rapid City, South Dakota 57701, United States
  • Nashville, Tennessee 37203, United States
  • Abilene, Texas 79606, United States
  • Ft Worth, Texas 76102, United States
  • Houston, Texas 77030, United States
  • San Antonio, Texas 78240, United States
  • Vancouver, British Columbia V5Z 3N9, Canada
  • Victoria, British Columbia V8V 4X3, Canada
  • Halifax, Nova Scotia B3H 2Y9, Canada
  • London, Ontario N6A 4V2, Canada
  • Mississauga, Ontario L4W 1W9, Canada
  • Toronto, Ontario M4N 3M5, Canada
  • Medellin, Antioquia, Colombia
  • Bogota, Colombia
  • Hyderabad, A.p. 500034, India
  • Bangalore, Karnataka 560010, India
  • Kolkata, West Bengal 700073, India
  • Kfar-Saba, 44281, Israel
  • Petah Tikva, 49100, Israel
  • Rehovot, 76100, Israel
  • Tel Aviv, 64239, Israel
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 27, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00943072
Lead sponsor
Regeneron Pharmaceuticals
Collaborators
Bayer
Responsible party
Sponsor
First posted
Jul 21, 2009
Start date
Jul 2009
Primary completion
Oct 2010
Completion
Apr 2012
Results posted
May 27, 2013
Last update
May 27, 2013

Study contacts

Clinical Trial Management
study director · Regeneron Pharmaceuticals

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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