Efficacy and Safety of Two Different Aflibercept Regimens in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02540954
• Collaborator: (none)
• Enrollment: 336
• Locations: 71
• Arms: 2
• Actual Duration (Months): 56.2
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To compare the efficacy of 2 mg aflibercept administered by two different intravitreal (IVT) treatment regimens to subjects with neovascular age-related macular degeneration (nAMD)

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)	Phase 3

Detailed Description

330 Patients who have completed at least one year of treatment with aflibercept will be randomized to two different aflibercept regimens and followed for 76 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 336 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Active-controlled, Parallel-group, Phase-3b Study of the Efficacy, Safety, and Tolerability of 2 mg Aflibercept Administered by Intravitreal Injections Using Two Different Treatment Regimens to Subjects With Neovascular Age-related Macular Degeneration (nAMD).
• Actual Study Start Date: Sep 29, 2015
• Actual Primary Completion Date: Dec 24, 2019
• Actual Study Completion Date: Jun 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aflibercept extended dosing Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); A dose of 2 mg aflibercept injected intravitreally
Active Comparator: Aflibercept 2Q8 (2 mg aflibercept administered every 8 weeks) Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); A dose of 2 mg aflibercept injected intravitreally

Outcome Measures

Primary Outcome Measures

1. Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye [From baseline to Week 52]

   Visual function was assessed with the procedure from the ETDRS adapted for the Age Related Eye Disease Study using charts with 70 letters at a starting distance of 4 meters. Charts are organized in 14 lines of decreasing size with 5 letters each. Participants reading up to 19 letters at 4 meters were tested at 1 meter to read the first 6 lines. The score equals the sum of letters read at 1 meter and 4 meters. If more than 19 letters are read at 4 meters the score equals the number of letters read plus 30. The score range is 0 to 100, and a higher score represents better visual function.

Secondary Outcome Measures

1. Percentage of Participants Maintaining Vision in the Study Eye [At week 52]

   A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline.

2. Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye [At week 52]

3. Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye [From baseline to week 52]

   Retinal characteristic was evaluated using Optical coherence tomography (OCT).

4. Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye [From baseline to week 52]

   Choroidal neovascularization measured by optical coherence tomography (OCT).

5. Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye [At week 52]

6. Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire [From baseline to week 52]

   National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) total score ranges from 0 to 100, where 100 represents the best possible score and 0 represents the worst.

7. Number of Participants With Treatment-emergent Adverse Events (TEAE) [Started after the first application of aflibercept in the study and less than or equal to 30 days after the last dose of study drug over approximately 1.5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 51 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The following criteria must have been met at the initial start of aflibercept treatment (i.e. start of aflibercept treatment at least 1 year before this study):

• Subject had primary subfoveal choroidal neovascularization (CNV) lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea, as evidenced by fluorescein angiography/photography (FA/FP) of the study eye within 3 weeks before the initiation of aflibercept treatment.

• The area of CNV occupied at least 50% of the total lesion within 3 weeks before the initiation of aflibercept treatment.

• Documented best-corrected visual acuity (BCVA) was 20/40 to 20/320 (letter score of 73 to 25) in the study eye at the initiation of treatment.

• Men and women >= 51 years of age

• The subject's history of aflibercept treatment meets ALL of the following:

• Treatment in the study eye was initiated with three monthly (-1 week/+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed

• Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks

Exclusion Criteria:

• Any prior or concomitant therapy with an investigational or approved agent to treat neovascular AMD in the study eye other than aflibercept.

• Total lesion size > 12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by fluorescein angiography (FA) in the study eye

• Subretinal hemorrhage that was:

1. 50% or more of the total lesion area, or

2. if the blood was under the fovea, and

3. the blood under the fovea was 1 or more disc areas in size in the study eye.

• Scar or fibrosis making up more than 50% of the total lesion in the study eye.

• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.

• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.

• Causes of CNV other than AMD in the study eye.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Wien		Austria	1090
2		Wien		Austria	1140
3		Toronto	Ontario	Canada	M4N 3M5
4	Clinique medicale de l'oeil de l'Estrie	Sherbrooke	Quebec	Canada	J1J 2B8
5		Hradec Kralove		Czechia	500 05
6		Plzen		Czechia	304 60
7		Praha 10		Czechia	100 34
8		Praha 2		Czechia	12808
9		Praha 5		Czechia	150 00
10		Paris	Cedex 12	France	75557
11		Bordeaux		France	33000
12		Dijon Cedex		France	BP 1542-21
13		Lyon Cedex 04		France	69317
14		Nice Cedex		France	06006
15		Paris		France	75010
16		Würzburg	Bayern	Germany	97080
17		Darmstadt	Hessen	Germany	64297
18		Frankfurt	Hessen	Germany	60596
19		Marburg	Hessen	Germany	35037
20		Göttingen	Niedersachsen	Germany	37075
21		Düsseldorf	Nordrhein-Westfalen	Germany	40225
22		Leipzig	Sachsen	Germany	04103
23		Berlin		Germany	10713
24		Berlin		Germany	12203
25		Hamburg		Germany	20251
26		Budapest		Hungary	1085
27		Debrecen		Hungary	4032
28		Pecs		Hungary	7621
29		Roma	Lazio	Italy	00133
30		Roma	Lazio	Italy	00198
31		Genova	Liguria	Italy	16132
32		Brescia	Lombardia	Italy	25015
33		Milano	Lombardia	Italy	20122
34		Milano	Lombardia	Italy	20132
35		Milano	Lombardia	Italy	20157
36		Torino	Piemonte	Italy	10122
37		Catania	Sicilia	Italy	95123
38		Pisa	Toscana	Italy	56124
39		Verona	Veneto	Italy	37134
40		Parma		Italy	43126
41		Kaunas		Lithuania	LT-50009
42		Vilnius		Lithuania	LT-08661
43		Gdansk		Poland	80-809
44		Olsztyn		Poland	10-424
45		Coimbra		Portugal	3000-548
46		Leiria		Portugal	2410-197
47		Lisboa		Portugal	1649-035
48		Porto		Portugal	4200-319
49		Bratislava		Slovakia	826 06
50		Bratislava		Slovakia	851 07
51		Nitra		Slovakia	949 01
52		L'Hospitalet de Llobregat	Barcelona	Spain	08907
53		Barcelona		Spain	08036
54		Valencia		Spain	46014
55		Bern		Switzerland
56		Genève		Switzerland	1204
57		Southampton	Hampshire	United Kingdom	SO16 6YD
58		Liverpool	Merseyside	United Kingdom	L7 8XP
59		Great Yarmouth	Norfolk	United Kingdom	NR31 6LA
60		Middlesborough	North Yorkshire	United Kingdom	TS4 3BW
61		Pontyclun	Rhondda, Cynon, Taff	United Kingdom	CF72 8XR
62		Guildford	Surrey	United Kingdom	GU2 7XX
63		Newcastle Upon Tyne	Tyne And Wear	United Kingdom	NE1 4LP
64		Sunderland	Tyne And Wear	United Kingdom	SR2 9HP
65		Rugby	Warwickshire	United Kingdom	CV22 5PX
66		Wakefield	West Yorkshire	United Kingdom	WF1 4DG
67		Hull	York	United Kingdom	HU3 2JZ
68		Colchester		United Kingdom	CO3 3NB
69		London		United Kingdom	NW1 5QH
70		London		United Kingdom	SE5 9RS
71		Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

• Study Protocol - Dec 10, 2015
• Statistical Analysis Plan - Jan 31, 2020

More Information

Additional Information:

• Click here to find results for studies related to Bayer products
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02540954
• Other Study ID Numbers: 16598; 2013-000120-33
• First Posted: Sep 4, 2015
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Bayer: Age-related macular degeneration (AMD); Eylea treatment; Treat and Extend; Intravitreal
• Additional relevant MeSH terms: Macular Degeneration; Aflibercept

Study Results

Participant Flow

Recruitment Details	Study was conducted at 76 centers in 14 countries or regions, between 29-SEP-2015 (first participant first visit) and 04-JUN-2020 (last participant last visit)
Pre-assignment Detail	At baseline, 336 participants were randomized to one of 2 treatment groups; 168 participants were randomized to the extended-dosing group and 168 participants were randomized to the 2Q8 (2 mg aflibercept administered every 8 weeks) group.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Period Title: Overall Study
STARTED	168	168
Treated	167	168
Post-baseline BCVA Assessment	165	167
COMPLETED	149	154
NOT COMPLETED	19	14

Baseline Characteristics

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	Total
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.	Total of all reporting groups
Overall Participants	167	168	335
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.3 (8.3)	74.7 (7.0)	75.5 (7.7)
Sex: Female, Male (Count of Participants)
Female	107 64.1%	108 64.3%	215 64.2%
Male	60 35.9%	60 35.7%	120 35.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	136 81.4%	128 76.2%	264 78.8%
Unknown or Not Reported	31 18.6%	40 23.8%	71 21.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	139 83.2%	132 78.6%	271 80.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	28 16.8%	36 21.4%	64 19.1%
Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual (Letters read correctly) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Letters read correctly]	69.0 (12.1)	70.1 (10.9)	69.6 (11.5)
Central retinal thickness (CRT) in the study eye (μm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μm]	257.3 (67.8)	264.4 (59.7)	260.9 (63.8)
Choroidal neovascularization (CNV) area in the study eye (mm*2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm*2]	4.695 (4.043)	5.060 (4.105)	4.875 (4.070)
Total score for National Eye Institute 25-Item Visual Function (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	72.889 (18.414)	75.757 (15.495)	74.340 (17.034)

Outcome Measures

1. Primary Outcome

Title	Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye
Description	Visual function was assessed with the procedure from the ETDRS adapted for the Age Related Eye Disease Study using charts with 70 letters at a starting distance of 4 meters. Charts are organized in 14 lines of decreasing size with 5 letters each. Participants reading up to 19 letters at 4 meters were tested at 1 meter to read the first 6 lines. The score equals the sum of letters read at 1 meter and 4 meters. If more than 19 letters are read at 4 meters the score equals the number of letters read plus 30. The score range is 0 to 100, and a higher score represents better visual function.
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Mean (Standard Deviation) [Letters read correctly]	-0.3 (7.5)	-0.5 (8.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aflibercept Extended Dosing, Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin is 5 letters.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -1.51 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Maintaining Vision in the Study Eye
Description	A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline.
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Number [Percentage of participants]	95.2 57%	94.0 56%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aflibercept Extended Dosing, Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non inferiority margin is 7%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference in %
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -3.7 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Number [Percentage of participants]	24.2 14.5%	21.0 12.5%

4. Secondary Outcome

Title	Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
Description	Retinal characteristic was evaluated using Optical coherence tomography (OCT).
Time Frame	From baseline to week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS) with number of participants evaluable for this specific end point.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Mean (Standard Deviation) [μm]	-24.4 (55.2)	-33.4 (47.1)

5. Secondary Outcome

Title	Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye
Description	Choroidal neovascularization measured by optical coherence tomography (OCT).
Time Frame	From baseline to week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS) with number of participants evaluable for this specific end point.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Mean (Standard Deviation) [mm*2]	0.274 (2.723)	0.204 (2.813)

6. Secondary Outcome

Title	Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS). The FAS included all randomized participants who received any study drug and had a baseline BCVA assessment and at least one post-baseline BCVA assessment.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Number [Percentage of participants]	0 0%	0.6 0.4%

7. Secondary Outcome

Title	Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire
Description	National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) total score ranges from 0 to 100, where 100 represents the best possible score and 0 represents the worst.
Time Frame	From baseline to week 52

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed based on full analysis set (FAS) with number of participants evaluable for this specific end point.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	165	167
Mean (Standard Deviation) [Score on a scale]	0.186 (9.601)	-1.694 (10.328)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aflibercept Extended Dosing, Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.880
	Confidence Interval	(2-Sided) 95%; -4.152 to 0.392
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time Frame	Started after the first application of aflibercept in the study and less than or equal to 30 days after the last dose of study drug over approximately 1.5 years

Outcome Measure Data

Analysis Population Description

Number of participants with TEAE was analyzed based on safety analysis set (SAF) with number of participants evaluable.

Arm/Group Title	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
Measure Participants	167	168
Any TEAE	130 77.8%	124 73.8%
Any serious TEAE	26 15.6%	23 13.7%

Adverse Events

Time Frame	From after the first application of aflibercept in the study to 30 days after the last dose of study drug over approximately 1.5 years.
Arm/Group Title	Aflibercept Extended Dosing		Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
Arm/Group Description	Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).		Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.
All Cause Mortality
	Aflibercept Extended Dosing		Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/167 (0%)		3/168 (1.8%)
Serious Adverse Events
	Aflibercept Extended Dosing		Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/167 (15.6%)		23/168 (13.7%)
Blood and lymphatic system disorders
Anaemia	0/167 (0%)	0	1/168 (0.6%)	1
Febrile neutropenia	0/167 (0%)	0	1/168 (0.6%)	1
Cardiac disorders
Acute myocardial infarction	1/167 (0.6%)	1	0/168 (0%)	0
Atrial fibrillation	2/167 (1.2%)	2	1/168 (0.6%)	1
Atrial flutter	0/167 (0%)	0	1/168 (0.6%)	1
Bradycardia	1/167 (0.6%)	1	0/168 (0%)	0
Cardiac failure	0/167 (0%)	0	1/168 (0.6%)	1
Coronary artery stenosis	0/167 (0%)	0	1/168 (0.6%)	1
Myocardial infarction	3/167 (1.8%)	3	0/168 (0%)	0
Eye disorders
Retinal haemorrhage	2/167 (1.2%)	2	0/168 (0%)	0
Retinal tear	1/167 (0.6%)	1	0/168 (0%)	0
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic	1/167 (0.6%)	1	0/168 (0%)	0
Intestinal perforation	1/167 (0.6%)	1	0/168 (0%)	0
Oedematous pancreatitis	0/167 (0%)	0	1/168 (0.6%)	1
Gastrointestinal vascular malformation haemorrhagic	0/167 (0%)	0	1/168 (0.6%)	1
General disorders
General physical health deterioration	1/167 (0.6%)	1	0/168 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/167 (0%)	0	1/168 (0.6%)	1
Cholelithiasis	1/167 (0.6%)	1	0/168 (0%)	0
Infections and infestations
Appendicitis	0/167 (0%)	0	1/168 (0.6%)	1
Endophthalmitis	1/167 (0.6%)	1	1/168 (0.6%)	1
Gastroenteritis	0/167 (0%)	0	1/168 (0.6%)	1
Pneumonia	2/167 (1.2%)	2	0/168 (0%)	0
Septic shock	0/167 (0%)	0	1/168 (0.6%)	1
Urinary tract infection	1/167 (0.6%)	1	0/168 (0%)	0
Wound infection	0/167 (0%)	0	1/168 (0.6%)	1
Urosepsis	1/167 (0.6%)	1	0/168 (0%)	0
Infectious pleural effusion	1/167 (0.6%)	1	0/168 (0%)	0
Injury, poisoning and procedural complications
Facial bones fracture	0/167 (0%)	0	1/168 (0.6%)	1
Fall	3/167 (1.8%)	3	0/168 (0%)	0
Femur fracture	0/167 (0%)	0	1/168 (0.6%)	1
Head injury	0/167 (0%)	0	1/168 (0.6%)	1
Humerus fracture	2/167 (1.2%)	2	1/168 (0.6%)	1
Joint dislocation	0/167 (0%)	0	1/168 (0.6%)	1
Cataract operation complication	1/167 (0.6%)	1	0/168 (0%)	0
Upper limb fracture	1/167 (0.6%)	1	0/168 (0%)	0
Peripheral arterial reocclusion	1/167 (0.6%)	1	0/168 (0%)	0
Toxicity to various agents	1/167 (0.6%)	1	0/168 (0%)	0
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	0/167 (0%)	0	1/168 (0.6%)	1
Osteoarthritis	1/167 (0.6%)	1	2/168 (1.2%)	2
Rotator cuff syndrome	1/167 (0.6%)	1	0/168 (0%)	0
Spinal osteoarthritis	0/167 (0%)	0	1/168 (0.6%)	1
Spinal stenosis	0/167 (0%)	0	1/168 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/167 (0%)	0	1/168 (0.6%)	1
Breast neoplasm	0/167 (0%)	0	1/168 (0.6%)	1
Lung adenocarcinoma	0/167 (0%)	0	1/168 (0.6%)	1
Renal cancer	0/167 (0%)	0	1/168 (0.6%)	1
Uterine cancer	0/167 (0%)	0	1/168 (0.6%)	1
Gastrointestinal tract adenoma	1/167 (0.6%)	1	0/168 (0%)	0
Nervous system disorders
Sciatica	0/167 (0%)	0	1/168 (0.6%)	1
Subarachnoid haemorrhage	0/167 (0%)	0	1/168 (0.6%)	1
Transient ischaemic attack	0/167 (0%)	0	2/168 (1.2%)	2
Trigeminal neuralgia	1/167 (0.6%)	1	0/168 (0%)	0
Ischaemic stroke	1/167 (0.6%)	1	0/168 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/167 (0.6%)	1	0/168 (0%)	0
Reproductive system and breast disorders
Prostatitis	0/167 (0%)	0	1/168 (0.6%)	1
Surgical and medical procedures
Oesophageal prosthesis insertion	0/167 (0%)	0	1/168 (0.6%)	1
Vascular disorders
Aortic stenosis	0/167 (0%)	0	1/168 (0.6%)	2
Peripheral artery occlusion	1/167 (0.6%)	1	0/168 (0%)	0
Other (Not Including Serious) Adverse Events
	Aflibercept Extended Dosing		Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/167 (35.9%)		70/168 (41.7%)
Eye disorders
Cataract	17/167 (10.2%)	22	19/168 (11.3%)	27
Visual acuity reduced	14/167 (8.4%)	18	4/168 (2.4%)	6
Choroidal neovascularisation	9/167 (5.4%)	10	9/168 (5.4%)	9
Subretinal fluid	14/167 (8.4%)	17	14/168 (8.3%)	16
Neovascular age-related macular degeneration	8/167 (4.8%)	9	10/168 (6%)	12
Infections and infestations
Influenza	9/167 (5.4%)	9	9/168 (5.4%)	9
Nasopharyngitis	4/167 (2.4%)	5	12/168 (7.1%)	15
Investigations
Intraocular pressure increased	7/167 (4.2%)	12	11/168 (6.5%)	19

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.