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Trial record 1 of 1 for:    vgfte-rvo-1027
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Study to Assess the Clinical Efficacy and Safety of Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) in Patients With Branch Retinal Vein Occlusion (BRVO) (VIBRANT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01521559
Recruitment Status : Completed
First Posted : January 30, 2012
Results First Posted : November 13, 2014
Last Update Posted : November 13, 2014
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Condition Branch Retinal Vein Occlusion
Interventions Procedure: Macular Laser Photocoagulation
Drug: Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Enrollment 183
Recruitment Details Participants with macular edema secondary to branch retinal vein occlusion (BRVO) involving the center of the macula in the study eye were eligible to participate in the study.
Pre-assignment Details Of 281 participants who were screened for inclusion in the study, 183 were enrolled (started) and 183 received treatment.
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Hide Arm/Group Description Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24. Participants received treatment with Intravitreal Aflibercept Injection (IAI) starting at week 24 if they met rescue criteria. Treatment with IAI once initiated was 3 initial monthly doses followed by Q8 week dosing. Participants received 2 milligrams (mg) Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24 followed by injections every 8 weeks (2Q8) through week 48. Participants in this group could receive laser rescue at week 36.
Period Title: Overall Study
Started 92 91
Completed Week 24 83 85
Completed Week 52 77 73
Completed 77 73
Not Completed 15 18
Reason Not Completed
Adverse Event             0             4
Death             1             0
Withdrawal by Subject             9             11
Lost to Follow-up             3             1
Protocol Violation             1             0
Other             1             2
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) Total
Hide Arm/Group Description Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24. Participants received treatment with Intravitreal Aflibercept Injection (IAI) starting at week 24 if they met rescue criteria. Treatment with IAI once initiated was 3 initial monthly doses followed by Q8 week dosing. Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24 followed by injections every 8 weeks (2Q8) through week 48. Participants in this group could receive laser rescue at week 36. Total of all reporting groups
Overall Number of Baseline Participants 90 91 181
Hide Baseline Analysis Population Description
Full analysis set (FAS): All enrolled subjects who received any investigational product, had a baseline best corrected visual acuity (BCVA) assessment, and at least 1 post-baseline BCVA assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants 91 participants 181 participants
63.9  (11.37) 67.0  (10.41) 65.5  (10.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 91 participants 181 participants
Female
36
  40.0%
47
  51.6%
83
  45.9%
Male
54
  60.0%
44
  48.4%
98
  54.1%
1.Primary Outcome
Title Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF
Hide Description Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at every visit from baseline through week 24. Last observation carried forward (LOCF) method was used to impute missing data.
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Hide Arm/Group Description:
Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24.
Overall Number of Participants Analyzed 90 91
Measure Type: Number
Unit of Measure: participants
24 48
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macular Laser Photocoagulation Treatment (Control), Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments P-value was calculated using 2-sided Cochran-Mantel-Haenszel test adjusted by regions (Japan vs North America) and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA >20/200).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 26.6
Confidence Interval (2-Sided) 95%
13.0 to 40.1
Estimation Comments Difference was IAI group minus laser group; Difference and confidence interval were calculated using Mantel-Haenszel weighting scheme adjusted by regions (Japan vs North America) and baseline BCVA (BCVA ≤20/200 and BCVA >20/200).
2.Secondary Outcome
Title Change From Baseline to Week 24 in BCVA Score - LOCF
Hide Description Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at every visit from baseline through week 24 - Last observation carried forward (LOCF) method was used to impute missing data.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Hide Arm/Group Description:
Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24.
Overall Number of Participants Analyzed 90 91
Mean (Standard Deviation)
Unit of Measure: letters correctly read
6.9  (12.91) 17.0  (11.88)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macular Laser Photocoagulation Treatment (Control), Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Comments Difference was IAI group minus laser group. P-value, Point estimate and 95% confidence interval (CI) were based on an analysis of covariance (ANCOVA) model with baseline measurement as covariate and treatment group, region, and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA >20/200) as fixed factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.5
Confidence Interval (2-Sided) 95%
7.1 to 14.0
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
Hide Description CRT was evaluated at every visit from baseline through week 24 using spectral domain Optical Coherence Tomography (OCT).
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Hide Arm/Group Description:
Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24
Overall Number of Participants Analyzed 90 91
Mean (Standard Deviation)
Unit of Measure: microns
-128.0  (195.02) -280.5  (189.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macular Laser Photocoagulation Treatment (Control), Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Comments Difference was IAI group minus laser group; P-value, Point estimate, and 95% CI, were based on an ANCOVA model with baseline measurement as covariate and treatment group, region, and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA >20/200) as fixed factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -148.6
Confidence Interval (2-Sided) 95%
-179.8 to -117.4
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) Questionnaire Total Score at Week 24 - LOCF
Hide Description 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 that are all scored from 0-100. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf.
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Hide Arm/Group Description:
Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24.
Overall Number of Participants Analyzed 87 88
Mean (Standard Deviation)
Unit of Measure: scores on a scale
6.3  (12.34) 7.7  (11.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macular Laser Photocoagulation Treatment (Control), Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Comments Difference was IAI group minus laser group; P-value, Point estimate, and 95% CI, were based on an ANCOVA model with baseline measurement as covariate and treatment group, region, and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA >20/200) as fixed factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0833
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-0.3 to 5.5
Estimation Comments [Not Specified]
Time Frame Through Week 52 (end of study)
Adverse Event Reporting Description The safety analysis set (SAF) included all enrolled participants who received any investigational product; it is based on the treatment received (as treated).
 
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Hide Arm/Group Description Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24. Participants received treatment with Intravitreal Aflibercept Injection (IAI) starting at week 24 if they met rescue criteria. Treatment with IAI once initiated was 3 initial monthly doses followed by Q8 week dosing. Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24 followed by injections every 8 weeks (2Q8) through week 48. Participants in this group could receive laser rescue at week 36.
All-Cause Mortality
Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Affected / at Risk (%) Affected / at Risk (%)
Total   10/92 (10.87%)   13/91 (14.29%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/92 (0.00%)  2/91 (2.20%) 
Cardiac disorders     
Atrial fibrillation * 1  0/92 (0.00%)  1/91 (1.10%) 
Atrial flutter * 1  1/92 (1.09%)  0/91 (0.00%) 
Atrioventricular block second degree * 1  0/92 (0.00%)  1/91 (1.10%) 
Bradycardia * 1  0/92 (0.00%)  1/91 (1.10%) 
Cardiac failure acute * 1  1/92 (1.09%)  0/91 (0.00%) 
Cardiomyopathy * 1  0/92 (0.00%)  1/91 (1.10%) 
Coronary artery disease * 1  0/92 (0.00%)  1/91 (1.10%) 
Myocardial infarction * 1  1/92 (1.09%)  0/91 (0.00%) 
Gastrointestinal disorders     
Gastritis * 1  0/92 (0.00%)  1/91 (1.10%) 
Intestinal fistula * 1  0/92 (0.00%)  1/91 (1.10%) 
Large intestine polyp * 1  0/92 (0.00%)  1/91 (1.10%) 
Small intestinal obstruction * 1  0/92 (0.00%)  1/91 (1.10%) 
General disorders     
Chest pain * 1  0/92 (0.00%)  1/91 (1.10%) 
Hernia * 1  1/92 (1.09%)  0/91 (0.00%) 
Non-cardiac chest pain * 1  1/92 (1.09%)  0/91 (0.00%) 
Infections and infestations     
Gastroenteritis * 1  0/92 (0.00%)  1/91 (1.10%) 
Osteomyelitis * 1  1/92 (1.09%)  0/91 (0.00%) 
Pelvic abscess * 1  0/92 (0.00%)  1/91 (1.10%) 
Pneumonia * 1  1/92 (1.09%)  2/91 (2.20%) 
Pyelonephritis * 1  0/92 (0.00%)  1/91 (1.10%) 
Injury, poisoning and procedural complications     
Cataract traumatic * 1 [1]  0/92 (0.00%)  1/91 (1.10%) 
Delayed haemolytic transfusion reaction * 1  0/92 (0.00%)  1/91 (1.10%) 
Road traffic accident * 1  1/92 (1.09%)  0/91 (0.00%) 
Investigations     
Transaminases increased * 1  0/92 (0.00%)  1/91 (1.10%) 
Metabolism and nutrition disorders     
Dehydration * 1  2/92 (2.17%)  0/91 (0.00%) 
Hypomagnesaemia * 1  1/92 (1.09%)  0/91 (0.00%) 
Musculoskeletal and connective tissue disorders     
Cervical spinal stenosis * 1  1/92 (1.09%)  0/91 (0.00%) 
Osteonecrosis * 1  1/92 (1.09%)  0/91 (0.00%) 
Spinal column stenosis * 1  1/92 (1.09%)  0/91 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer metastatic * 1  0/92 (0.00%)  1/91 (1.10%) 
Lung adenocarcinoma * 1  0/92 (0.00%)  1/91 (1.10%) 
Squamous cell carcinoma * 1  0/92 (0.00%)  1/91 (1.10%) 
Nervous system disorders     
Cerebrovascular accident * 1  1/92 (1.09%)  0/91 (0.00%) 
Hypoaesthesia * 1  0/92 (0.00%)  1/91 (1.10%) 
Presyncope * 1  0/92 (0.00%)  1/91 (1.10%) 
Subarachnoid haemorrhage * 1  1/92 (1.09%)  0/91 (0.00%) 
Syncope * 1  1/92 (1.09%)  0/91 (0.00%) 
Renal and urinary disorders     
Hydronephrosis * 1  0/92 (0.00%)  1/91 (1.10%) 
Nephrolithiasis * 1  0/92 (0.00%)  1/91 (1.10%) 
Renal failure * 1  1/92 (1.09%)  0/91 (0.00%) 
Renal failure acute * 1  1/92 (1.09%)  1/91 (1.10%) 
Vascular disorders     
Aortic stenosis * 1  1/92 (1.09%)  0/91 (0.00%) 
Hypertension * 1  1/92 (1.09%)  1/91 (1.10%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
[1]
Study eye
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Affected / at Risk (%) Affected / at Risk (%)
Total   30/92 (32.61%)   25/91 (27.47%) 
Eye disorders     
Conjunctival haemorrhage * 1 [1]  14/92 (15.22%)  22/91 (24.18%) 
Eye irritation * 1 [1]  1/92 (1.09%)  7/91 (7.69%) 
Eye pain * 1 [1]  7/92 (7.61%)  5/91 (5.49%) 
Infections and infestations     
Bronchitis * 1  2/92 (2.17%)  6/91 (6.59%) 
Nasopharyngitis * 1  8/92 (8.70%)  8/91 (8.79%) 
Urinary tract infection * 1  7/92 (7.61%)  3/91 (3.30%) 
Investigations     
Blood pressure increased * 1  5/92 (5.43%)  4/91 (4.40%) 
Vascular disorders     
Hypertension * 1  15/92 (16.30%)  9/91 (9.89%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
[1]
Study eye
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Without the prior written agreement of the Sponsor, the Institution (I) shall not publish, submit or present for publication, directly or indirectly, any Manuscript (M) prior to publication of an article in a peer-reviewed scientific journal summarizing data generated by all Study centers, unless no such article is so published before the first anniversary of the finalization of the clinical study report, in which case the (I) may publish or submit for publication a (M) without further delay.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trials Administrator
Organization: Regeneron
Phone: 914 847 5385
EMail: clinicaltrials@regeneron.com
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01521559    
Other Study ID Numbers: VGFTe-RVO-1027
First Submitted: January 26, 2012
First Posted: January 30, 2012
Results First Submitted: November 5, 2014
Results First Posted: November 13, 2014
Last Update Posted: November 13, 2014