Study to Assess the Clinical Efficacy and Safety of Intra... | NCT01521559

Name	Class
Bayer	INDUSTRY

Label	Type	Description	Intervention Names
Macular Laser Photocoagulation Treatment (Control)	Sham Comparator	Participants will receive macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24. Participants will receive 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.	Procedure: Macular Laser Photocoagulation
Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4	Experimental	Participants will receive 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 may receive laser rescue at week 36.	Drug: Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)

Name	Type	Description	Arm Group Labels	Other Names
Macular Laser Photocoagulation	Procedure		Macular Laser Photocoagulation Treatment (Control)
Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)

Measure	Description	Time Frame
Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF	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.	Baseline to week 24

Measure	Description	Time Frame
Change From Baseline to Week 24 in BCVA Score - LOCF	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.	Baseline to Week 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The following inclusion criteria include, but are not limited to:

Adults ≥ 18 years of age with foveal center-involved macular edema (ME) secondary to BRVO diagnosed within 12 months before the screening visit
ETDRS BCVA: letter score of 73 to 24 (20/40 to 20/320) in the study eye at screening and at day 1
Provide signed informed consent

Exclusion Criteria:

The following exclusion criteria include, but are not limited to:

Current bilateral manifestation of BRVO
Uncontrolled glaucoma defined as ≥ 25 mmHg on optimal medical regimen, or previous filtration surgery in either the study eye or the fellow eye
Insufficient clearing of macular hemorrhage that would prevent the patient from receiving laser treatment safely on day 1 (patients that meet this criterion may be rescreened once the macular hemorrhage resolves)
Uncontrolled diabetes mellitus (DM)
Previous use of intraocular corticosteroids or anti-angiogenic drugs in the study eye
Use of periocular corticosteroids in the study eye within 3 months before day 1
Use of intraocular or periocular corticosteroids or anti-angiogenic drugs in the fellow eye within 3 months before day 1
Previous administration of systemic anti-angiogenic medications
Panretinal scatter photocoagulation, sector laser photocoagulation, or macular grid photocoagulation in the study eye

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

PubMed Identifier	Type	Citation	Retractions
32633861	Derived	Shalchi Z, Mahroo O, Bunce C, Mitry D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD009510. doi: 10.1002/14651858.CD009510.pub3.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Macular Laser Photocoagulation Treatment (Control)	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF

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.

FAS

Posted

Number

participants

Baseline to week 24

ID	Title	Description
OG000	Macular Laser Photocoagulation Treatment (Control)	Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
OG001	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)	Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24.

Units	Counts
Participants	OG00090 OG00191

Title

Denominators

Categories

Title	Measurements
	OG00024 OG00148

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		Cochran-Mantel-Haenszel		0.0003	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).	Mean Difference (Net)	26.6			2-Sided	95	13.0	40.1			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).	No	Superiority or Other

Secondary

Change From Baseline to Week 24 in BCVA Score - LOCF

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.

FAS

Posted

Mean

Standard Deviation

letters correctly read

Baseline to Week 24

ID	Title	Description
OG000	Macular Laser Photocoagulation Treatment (Control)	Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
OG001	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)	Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24.

Units	Counts
Participants	OG000

Secondary

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

CRT was evaluated at every visit from baseline through week 24 using spectral domain Optical Coherence Tomography (OCT).

FAS

Posted

Mean

Standard Deviation

microns

Baseline to week 24

ID	Title	Description
OG000	Macular Laser Photocoagulation Treatment (Control)	Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
OG001	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)	Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24

Units	Counts
Participants	OG000

Secondary

Change From Baseline in the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) Questionnaire 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 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.

FAS

Posted

Mean

Standard Deviation

scores on a scale

Baseline to week 24

ID	Title	Description
OG000	Macular Laser Photocoagulation Treatment (Control)	Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24.
OG001	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)	Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0012 affected91 at risk
Aortic stenosis	Vascular disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Atrial flutter	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Bradycardia	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Cardiomyopathy	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Cataract traumatic	Injury, poisoning and procedural complications	MedDRA 16.1	Non-systematic Assessment	Study eye	EG0000 affected92 at risk EG0011 affected91 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Chest pain	General disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Coronary artery disease	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 16.1	Non-systematic Assessment		EG0002 affected92 at risk EG0010 affected91 at risk
Delayed haemolytic transfusion reaction	Injury, poisoning and procedural complications	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Gastritis	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Gastroenteritis	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Hernia	General disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Hypertension	Vascular disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0011 affected91 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Intestinal fistula	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Myocardial infarction	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Non-cardiac chest pain	General disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Osteomyelitis	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Pelvic abscess	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Pneumonia	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0012 affected91 at risk
Presyncope	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Pyelonephritis	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Renal failure	Renal and urinary disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0011 affected91 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Syncope	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment		EG0001 affected92 at risk EG0010 affected91 at risk
Transaminases increased	Investigations	MedDRA 16.1	Non-systematic Assessment		EG0000 affected92 at risk EG0011 affected91 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Blood pressure increased	Investigations	MedDRA 16.1	Non-systematic Assessment		EG0005 affected92 at risk EG0014 affected91 at risk
Bronchitis	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0002 affected92 at risk EG0016 affected91 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 16.1	Non-systematic Assessment	Study eye	EG00014 affected92 at risk EG00122 affected91 at risk
Eye irritation	Eye disorders	MedDRA 16.1	Non-systematic Assessment	Study eye	EG0001 affected92 at risk EG0017 affected91 at risk
Eye pain	Eye disorders	MedDRA 16.1	Non-systematic Assessment	Study eye	EG0007 affected92 at risk EG0015 affected91 at risk
Hypertension	Vascular disorders	MedDRA 16.1	Non-systematic Assessment		EG00015 affected92 at risk EG0019 affected91 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0008 affected92 at risk EG0018 affected91 at risk
Urinary tract infection	Infections and infestations	MedDRA 16.1	Non-systematic Assessment		EG0007 affected92 at risk EG0013 affected91 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Phoenix	Arizona		United States

ID	Term
D012164	Retinal Diseases
D005128	Eye Diseases
D020246	Venous Thrombosis
D013927	Thrombosis
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	Macular Laser Photocoagulation Treatment (Control)	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.
BG001	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Macular Laser Photocoagulation Treatment (Control)	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.			10	92	30	92
EG001	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)	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.			13	91	25	91