Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central Retinal Vein Occlusion (CRVO)
Official Title
A Randomized, Double-masked, Sham-controlled Phase 3 Study of the Efficacy, Safety and Tolerability of Repeated Intravitreal Administration of VEGF Trap-Eye in Subjects With Macular Edema Secondary to Central Retinal Vein Occlusion (CRVO)
Acronym
GALILEO
Organization
BayerINDUSTRY
Status Module
Record Verification Date
Oct 2014
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 2009
Primary Completion Date
Feb 2011Actual
Completion Date
Feb 2012Actual
First Submitted Date
Oct 30, 2009
First Submission Date that Met QC Criteria
Nov 12, 2009
First Posted Date
Nov 13, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 23, 2012
Results First Submitted that Met QC Criteria
Oct 23, 2012
Results First Posted Date
Nov 22, 2012Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 26, 2012
Certification/Extension First Submitted that Passed QC Review
Jan 26, 2012
Certification/Extension First Posted Date
Jan 30, 2012Estimated
Last Update Submitted Date
Oct 27, 2014
Last Update Posted Date
Nov 3, 2014Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
BayerINDUSTRY
Collaborators
Name
Class
Regeneron Pharmaceuticals
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
To determine the efficacy of vascular endothelial growth factor (VEGF) Trap-Eye injected into the eye on vision function in subjects with macular edema as a consequence of central retinal vein occlusion
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Intravitreal injection. Weeks 0 to 20 of Aflibercept Injection every 4 weeks; Weeks 24 to 52 every 4 weeks PRN (pro re nata, on demand); plus additional on Week 60 and 68.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 24 With Discontinued Participants Before Week 24 Evaluated as Failures
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed.
Baseline and Week 24
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in BCVA as Measured by Early Treatment Diabetic Retinopathy Study (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. However, because this was assessed at the screening visit, subjects may have had a higher BCVA recorded at the baseline visit and would not have been excluded from the study.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Center-involved macular edema secondary to central retinal vein occlusion (CRVO) for no longer than 9 months with mean central subfield thickness ≥ 250 μm on optical coherence tomography (OCT)
Adults ≥ 18 years
Early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) of 20/40 to 20/320 (73 to 24 letters) in the study eye
Exclusion Criteria:
Any prior treatment with anti-VEGF agents in the study eye (Pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc.) or previous administration of systemic anti-angiogenic medications
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
Holz FG, Roider J, Ogura Y, Korobelnik JF, Simader C, Groetzbach G, Vitti R, Berliner AJ, Hiemeyer F, Beckmann K, Zeitz O, Sandbrink R. VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol. 2013 Mar;97(3):278-84. doi: 10.1136/bjophthalmol-2012-301504. Epub 2013 Jan 7.
Aflibercept Injection First, Then Aflibercept Injection
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
Baseline and Week 24
Percentage of Participants Who Developed Neovascularization During the First 24 Weeks
Formation of blood vessels in the anterior segment, optic disc, or elsewhere in the fundus up to Week 24
From baseline until Week 24
Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 24 - LOCF
The NEI VFQ-25 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
Baseline and Week 24
Change From Baseline in European Five-dimensional Health Scale (EQ-5D) Score at Week 24 - LOCF
EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best).
Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U, Lorenz K, Honda M, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014 Jan;121(1):202-208. doi: 10.1016/j.ophtha.2013.08.012. Epub 2013 Sep 29.
FG001
Sham Treatment First, Then Aflibercept Injection
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
FG000106 subjects
FG00171 subjects
Participants Received Treatment
FG000104 subjectsSafety Population: Participants received treatment
FG00168 subjectsSafety Population: Participants received treatment
Fulfilled Requirements of FAS Population
FG000103 subjectsFull Analysis Set (FAS) Population: Participants received treatment with post baseline measurements
FG00168 subjectsFull Analysis Set (FAS) Population: Participants received treatment with post baseline measurements
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
BG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000104
BG00168
BG002172
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00060.0± 12.3
BG00163.8± 13.3
BG00261.5± 12.8
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00045
BG00131
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0004
BG0011
BG002
Baseline Best Corrected Visual Acuity (BCVA) letter scores
Infiormation retrieved from all baseline participants. Only participants with a ETDRS (Early Treatment Diabetic Retinopathy Study) Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters were included; a higher score represents better functioning.
Mean
Standard Deviation
Letters correctly read
Title
Denominators
Categories
Title
Measurements
BG00053.5± 15.7
BG001
Number of participants with baseline retinal perfusion
Retinal perfusion defined as less than 10 disc areas of capillary nonperfusion using fluorescein angiography (FA)
Number
Participants
Title
Denominators
Categories
Perfused
Title
Measurements
BG00090
BG00154
Baseline Retinal Thickness by Optical Coherence Tomography (OCT)
Mean
Standard Deviation
microns
Title
Denominators
Categories
Title
Measurements
BG000682.78± 233.36
BG001638.66± 224.69
BG002
Baseline intraocular pressure
Mean
Standard Deviation
mm Hg
Title
Denominators
Categories
Title
Measurements
BG00015.2± 2.8
BG00114.4± 2.7
BG002
Number of participants with time since Central retinal vein occlusion (CRVO) diagnosis
Number
Participants
Title
Denominators
Categories
>= 2 months
Title
Measurements
BG00046
BG00133
BG002
Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) total score
The NEI VFQ-25 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.
Mean
Standard Deviation
scores on a scale
Title
Denominators
Categories
Title
Measurements
BG00079.66± 13.06
BG001
European questionnaire 5 dimensions (EQ-5D) total score
The EQ-5D total score ranges from -0.594 to 1.000 with -0.594 being the worst.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
Title
Measurements
BG0000.87± 0.15
BG0010.86± 0.16
Race
Number
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG00026
BG00115
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 24 With Discontinued Participants Before Week 24 Evaluated as Failures
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed.
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
OG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Units
Counts
Participants
OG000103
OG00168
Title
Denominators
Categories
Title
Measurements
OG00060.2
OG00122.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Null hypothesis of difference of Eylea minus Sham of 0 was tested. In the database close after Week 24, basis for primary efficacy evaluation, 56 Sham / 96 Eylea subjects were considered as week 24 completers.
Cochran-Mantel-Haenszel
<.0001
CMH adjusted difference
38.3
2-Sided
95
24.4
52.1
The estimate is calculated as Eylea minus Sham. A positive value shows Eylea showed a higher BCVA total score compared to Sham.
No
Superiority or Other
Secondary
Change From Baseline in BCVA as Measured by Early Treatment Diabetic Retinopathy Study (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. However, because this was assessed at the screening visit, subjects may have had a higher BCVA recorded at the baseline visit and would not have been excluded from the study.
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
OG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Secondary
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
Full-Analysis Set with assessment for this outcome measure; imputation technique: LOCF
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
OG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Units
Counts
Participants
Secondary
Percentage of Participants Who Developed Neovascularization During the First 24 Weeks
Formation of blood vessels in the anterior segment, optic disc, or elsewhere in the fundus up to Week 24
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
OG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Units
Counts
Participants
Secondary
Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 24 - LOCF
The NEI VFQ-25 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
Full-Analysis Set with assessment for this outcome measure; imputation technique: LOCF
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
OG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Secondary
Change From Baseline in European Five-dimensional Health Scale (EQ-5D) Score at Week 24 - LOCF
EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best).
Full-Analysis Set with assessment for this outcome measure; imputation technique: LOCF
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.
OG001
Sham Treatment
Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.
Units
Counts
Time Frame
Not provided
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Aflibercept Injection (Until Week 20)
Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20. Participants were observed until Week 24. Participants in the safety population were at risk.
8
104
52
104
EG001
Sham Treatment (Until Week 20)
Participants received sham treatment administered every 4 weeks from Day 1 through Week 20. Participants were observed until Week 24. Participants in the safety population were at risk.
8
68
44
68
EG002
Aflibercept Injection (Until Week 48)
Participants who continued the study drug until Week 24 received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Participants were observed from Week 24 until Week 52. Participants in the safety population that completed Week 24 were at risk.
14
97
66
97
EG003
Sham Treatment (Until Week 48)
Participants who continued the study drug until Week 24 received sham treatment administered every 4 weeks from Week 24 to Week 48. Participants were observed from Week 24 until Week 52. Participants in the safety population that completed Week 24 were at risk.
7
57
30
57
EG004
Aflibercept Injection Continued (Until Week 68)
Participants on IAI who continued the study drug until Week 52, received 2 mg dose of IAI depending on the study retreatment criteria at Week 52, 60 and 68. Participants were observed starting from Week 52. Participants in the safety population that completed Week 52 were at risk.
4
91
38
91
EG005
Sham Treatment Then Aflibercept Injection (Until Week 68)
Participants on sham treatment switched to IAI, received a 2 mg dose of IAI at Week 52 and depending on the study retreatment criteria at Week 60 and 68. Participants were observed starting from Week 52. Participants in the safety population that completed Week 52 were at risk.
3
52
19
52
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Aortic valve incompetence
Cardiac disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG0030 affected57 at risk
EG0040 affected91 at risk
EG0051 affected52 at risk
Cardiac failure
Cardiac disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Coronary artery stenosis
Cardiac disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Diastolic dysfunction
Cardiac disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Mitral valve incompetence
Cardiac disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Blindness unilateral
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Glaucoma
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Iris neovascularisation
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Macular fibrosis
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Macular ischaemia
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Macular oedema
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0012 affected68 at risk
EG0024 affected97 at risk
EG003
Retinal vein occlusion
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Visual acuity reduced
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0021 affected97 at risk
EG003
Vitreous detachment
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Vitreous haemorrhage
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0021 affected97 at risk
EG003
Diverticular perforation
Gastrointestinal disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Hepatic function abnormal
Hepatobiliary disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Furuncle
Infections and infestations
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0021 affected97 at risk
EG003
Vestibular neuronitis
Infections and infestations
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Hand fracture
Injury, poisoning and procedural complications
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0021 affected97 at risk
EG003
Radius fracture
Injury, poisoning and procedural complications
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Spinal compression fracture
Injury, poisoning and procedural complications
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Spinal column stenosis
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Oropharyngeal cancer stage unspecified
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Syncope
Nervous system disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Laryngeal granuloma
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Pulmonary hypertension
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Ischaemic heart disease prophylaxis
Surgical and medical procedures
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Circulatory collapse
Vascular disorders
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0010 affected68 at risk
EG0020 affected97 at risk
EG0033 affected57 at risk
EG0040 affected91 at risk
EG0050 affected52 at risk
Conjunctival haemorrhage
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG00010 affected104 at risk
EG0013 affected68 at risk
EG0023 affected97 at risk
EG003
Eye irritation
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0003 affected104 at risk
EG0017 affected68 at risk
EG0024 affected97 at risk
EG003
Eye pain
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG00012 affected104 at risk
EG0013 affected68 at risk
EG0026 affected97 at risk
EG003
Foreign body sensation in eyes
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0006 affected104 at risk
EG0015 affected68 at risk
EG0022 affected97 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0003 affected104 at risk
EG0014 affected68 at risk
EG0023 affected97 at risk
EG003
Macular fibrosis
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0011 affected68 at risk
EG0025 affected97 at risk
EG003
Macular ischaemia
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0007 affected104 at risk
EG0015 affected68 at risk
EG0023 affected97 at risk
EG003
Macular oedema
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0002 affected104 at risk
EG0019 affected68 at risk
EG00230 affected97 at risk
EG003
Ocular hyperaemia
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0005 affected104 at risk
EG0014 affected68 at risk
EG0022 affected97 at risk
EG003
Optic disc vascular disorder
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0005 affected104 at risk
EG0013 affected68 at risk
EG0023 affected97 at risk
EG003
Retinal exudates
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0008 affected104 at risk
EG0015 affected68 at risk
EG0024 affected97 at risk
EG003
Retinal haemorrhage
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0004 affected104 at risk
EG0016 affected68 at risk
EG00211 affected97 at risk
EG003
Retinal vascular disorder
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0006 affected104 at risk
EG0017 affected68 at risk
EG00210 affected97 at risk
EG003
Visual acuity reduced
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0002 affected104 at risk
EG0017 affected68 at risk
EG00210 affected97 at risk
EG003
Vitreous detachment
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0002 affected104 at risk
EG0011 affected68 at risk
EG0027 affected97 at risk
EG003
Vitreous floaters
Eye disorders
MedDRA (14.1)
Non-systematic Assessment
EG0006 affected104 at risk
EG0010 affected68 at risk
EG0021 affected97 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0020 affected97 at risk
EG003
Influenza
Infections and infestations
MedDRA (14.1)
Non-systematic Assessment
EG0002 affected104 at risk
EG0010 affected68 at risk
EG0025 affected97 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (14.1)
Non-systematic Assessment
EG0008 affected104 at risk
EG0016 affected68 at risk
EG00210 affected97 at risk
EG003
Intraocular pressure increased
Investigations
MedDRA (14.1)
Non-systematic Assessment
EG0009 affected104 at risk
EG0014 affected68 at risk
EG00214 affected97 at risk
EG003
Visual acuity tests abnormal
Investigations
MedDRA (14.1)
Non-systematic Assessment
EG0000 affected104 at risk
EG0011 affected68 at risk
EG0025 affected97 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Non-systematic Assessment
EG0001 affected104 at risk
EG0015 affected68 at risk
EG0022 affected97 at risk
EG003
Headache
Nervous system disorders
MedDRA (14.1)
Non-systematic Assessment
EG0007 affected104 at risk
EG0014 affected68 at risk
EG0024 affected97 at risk
EG003
Hypertension
Vascular disorders
MedDRA (14.1)
Non-systematic Assessment
EG0004 affected104 at risk
EG0013 affected68 at risk
EG0024 affected97 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Publishing of result communication only after Bayer´s written approval. Manuscript to Bayer sixty days before public release. If no written Bayer comment within 60 days consider approval given. If multi-site study, principal investigator (PI) not do independently publish results before publication of the multi-site paper, but PI not restricted from 24 months from study to completion onwards.
Point of Contact
Title
Organization
Phone
Extension
Email
Therapeutic Area Head
BAYER
clinical-trials-contact@bayerhealthcare.com
ID
Term
D012170
Retinal Vein Occlusion
D008269
Macular Edema
Ancestor Terms
ID
Term
D012164
Retinal Diseases
D005128
Eye Diseases
D020246
Venous Thrombosis
D013927
Thrombosis
D016769
Embolism and Thrombosis
D014652
Vascular Diseases
D002318
Cardiovascular Diseases
D008268
Macular Degeneration
D012162
Retinal Degeneration
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C533178
aflibercept
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
76
Male
BG00059
BG00137
BG00296
5
Not Hispanic or Latino
BG000100
BG00166
BG002166
Unknown or Not Reported
BG0000
BG0011
BG0021
50.9
± 15.4
BG00252.5± 15.6
BG002
144
Nonperfused
Title
Measurements
BG0007
BG0017
BG00214
Indeterminate
Title
Measurements
BG0007
BG0017
BG00214
665.34
± 230.33
14.9
± 2.8
79
< 2 months
Title
Measurements
BG00056
BG00135
BG00291
Missing
Title
Measurements
BG0002
BG0010
BG0022
78.94
± 14.00
BG00279.38± 13.40
BG0020.87± 0.15
41
White
Title
Measurements
BG00075
BG00149
BG002124
Unknown or Not Reported
Title
Measurements
BG0003
BG0014
BG0027
Units
Counts
Participants
OG000103
OG00168
Title
Denominators
Categories
Title
Measurements
OG00071.6± 17.1
OG00154.3± 20.2
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Null hypothesis was equality in change from baseline to Week 24 in BCVA total letter score between Eylea and Sham. If primary efficacy was successful, secondary efficacy endpoints were tested in a pre-specified fixed sequence testing procedure. Change in BCVA letter score was to be tested first in this sequence.
ANOVA
ANOVA, adjusting for region and baseline BCVA category as fixed factors.
<.0001
As primary efficacy evaluation was significant, and this p-value was below significance level of two-sided <.05, the fixed sequence testing did continue with next secondary endpoint.
Difference in Least square means
14.7
2-Sided
95
10.8
18.7
The difference is calculated as Eylea minus Sham. A positive value indicates Eylea showed a higher change in BCVA total score until week 24 compared to Sham.
No
Superiority or Other
OG000103
OG00167
Title
Denominators
Categories
Title
Measurements
OG000-448.58± 256.02
OG001-169.27± 224.72
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Null hypothesis was equality in change from baseline to Week 24 in central retinal thickness between Eylea and Sham. If primary efficacy was successful, secondary efficacy end points were to be tested in a pre-specified fixed sequence testing procedure. Change in central retinal thickness was to be tested at second place in this sequence.
ANCOVA
ANCOVA, stratified by region and baseline BCVA category, baseline central retinal thickness added as covariate.
<.0001
As fixed sequence testing did reject nullhypothesis of change from baseline in BCVA until week 24, and this p-value was below significance level of two-sided <.05, the fixed sequence testing did continue with next secondary endpoint.
Difference in Least square (LS) means
-239.42
2-Sided
95
-286.31
-192.53
The difference is calculated as Eylea minus Sham. A negative value indicates Eylea showed a higher reduction in change in central retinal thickness until week 24 compared to Sham.
No
Superiority or Other
OG000103
OG00168
Title
Denominators
Categories
Any neovascularization
Title
Measurements
OG0002.9
OG0014.4
Anterior segment neovascularization
Title
Measurements
OG0001.9
OG0011.5
Neovascularization of the optic disc (NVD)
Title
Measurements
OG0000.0
OG0010.0
Neovascularization elsewhere in the fundus (NVE)
Title
Measurements
OG0001.0
OG0012.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Nullhypothesis of no difference in development of neovascularizations between Eylea and Sham group was tested. (Any neovascularization)
Cochran-Mantel-Haenszel
Cochrane-Mantel-Haenszel test, stratified by region and baseline BCVA category.
0.5947
As fixed sequence testing did reject nullhypothesis of change from baseline in CRT until week 24, and this p-value was not below significance level of two-sided <.05, the fixed sequence testing did end with this evaluation.
CMH adjusted Difference
-1.5
2-Sided
95
-7.4
4.4
No
Superiority or Other
Units
Counts
Participants
OG00096
OG00165
Title
Denominators
Categories
Title
Measurements
OG0007.46± 9.55
OG0013.55± 9.74
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in LS means
4.2
2-Sided
95
1.7
6.8
As the fixed sequence of secondary endpoints stopped with proportion of neovascularizations developed until week 24, 95% confidence interval is only of descriptive nature.
No
Superiority or Other
Participants
OG00095
OG00164
Title
Denominators
Categories
Title
Measurements
OG0000.029± 0.139
OG001-0.002± 0.195
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in LS Means
0.044
2-Sided
95
-0.002
0.09
As the fixed sequence of secondary endpoints stopped with proportion of neovascularizations developed until week 24, 95% confidence interval is only of descriptive nature.