Trial Outcomes & Findings for Japanese Treat and Extend Study of Aflibercept in Neovascular Age-related Macular Degeneration (NCT NCT02305238)
NCT ID: NCT02305238
Last Updated: 2023-11-18
Results Overview
Visual functions of the study eye (at every visit) and the fellow eye were assessed, according to the ETDRS protocol as described in detail in the operation manual. A higher score represents better functioning.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
288 participants
Primary outcome timeframe
Baseline and Week 52
Results posted on
2023-11-18
Participant Flow
Study was conducted in Japan between 19 December 2014 (first participant first visit) and 08 November 2017 (last participant last visit).
288 participants were enrolled and 255 entered run-in phase. 8 were randomization failures. 247 participants were randomized (2 Weeks \[2W\] adjustment group: 124; 4 Weeks \[4W\] adjustment group: 123) at Week 16. All 247 participant:s were treated and 227 participants (111 in the 2W adjustment, 116 in the 4W adjustment) completed Week 52 treatment.
Participant milestones
| Measure |
2 Weeks Adjustment
Participants received Aflibercept Intravitreal (IVT) injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
Randomization Failure
Participants entered run-in phase but discontinued the study before randomization after receiving at least one injection.
|
|---|---|---|---|
|
Overall Study
STARTED
|
124
|
123
|
8
|
|
Overall Study
Treated
|
124
|
123
|
7
|
|
Overall Study
Randomized
|
124
|
123
|
0
|
|
Overall Study
BCVA Post-randomization Assessment
|
123
|
123
|
0
|
|
Overall Study
COMPLETED
|
108
|
104
|
0
|
|
Overall Study
NOT COMPLETED
|
16
|
19
|
8
|
Reasons for withdrawal
| Measure |
2 Weeks Adjustment
Participants received Aflibercept Intravitreal (IVT) injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
Randomization Failure
Participants entered run-in phase but discontinued the study before randomization after receiving at least one injection.
|
|---|---|---|---|
|
Overall Study
Death
|
2
|
1
|
0
|
|
Overall Study
Progressive disease
|
4
|
4
|
0
|
|
Overall Study
Logistical difficulties
|
1
|
3
|
0
|
|
Overall Study
Protocol Violation
|
0
|
3
|
0
|
|
Overall Study
Physician Decision
|
2
|
1
|
0
|
|
Overall Study
Adverse Event
|
4
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
3
|
4
|
0
|
|
Overall Study
Randomized failure
|
0
|
0
|
8
|
|
Overall Study
Required procedure failed
|
0
|
1
|
0
|
Baseline Characteristics
Participants in SAF with data available for central retinal thickness
Baseline characteristics by cohort
| Measure |
2 Weeks Adjustment
n=124 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
Randomization Failure
n=7 Participants
Participants entered run-in phase but discontinued the study before randomization after receiving at least one injection.
|
Total
n=254 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
73.0 years
STANDARD_DEVIATION 7.9 • n=124 Participants
|
75.0 years
STANDARD_DEVIATION 8.1 • n=123 Participants
|
80.3 years
STANDARD_DEVIATION 7.8 • n=7 Participants
|
74.2 years
STANDARD_DEVIATION 8.1 • n=254 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=124 Participants
|
32 Participants
n=123 Participants
|
1 Participants
n=7 Participants
|
69 Participants
n=254 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=124 Participants
|
91 Participants
n=123 Participants
|
6 Participants
n=7 Participants
|
185 Participants
n=254 Participants
|
|
Best-corrected visual acuity (BCVA)
|
54.6 letters
STANDARD_DEVIATION 13.1 • n=124 Participants
|
55.3 letters
STANDARD_DEVIATION 12.0 • n=123 Participants
|
54.9 letters
STANDARD_DEVIATION 17.9 • n=7 Participants
|
55.0 letters
STANDARD_DEVIATION 12.7 • n=254 Participants
|
|
Central Retinal Thickness
|
386.5 μm
STANDARD_DEVIATION 158.6 • n=123 Participants • Participants in SAF with data available for central retinal thickness
|
370.3 μm
STANDARD_DEVIATION 120.0 • n=121 Participants • Participants in SAF with data available for central retinal thickness
|
371.6 μm
STANDARD_DEVIATION 88.5 • n=7 Participants • Participants in SAF with data available for central retinal thickness
|
378.3 μm
STANDARD_DEVIATION 139.4 • n=251 Participants • Participants in SAF with data available for central retinal thickness
|
|
Choroidal neovascularization
No CNV
|
0 Participants
n=124 Participants
|
1 Participants
n=123 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=254 Participants
|
|
Choroidal neovascularization
Classic CNV
|
35 Participants
n=124 Participants
|
42 Participants
n=123 Participants
|
1 Participants
n=7 Participants
|
78 Participants
n=254 Participants
|
|
Choroidal neovascularization
Classic & Occult
|
15 Participants
n=124 Participants
|
17 Participants
n=123 Participants
|
2 Participants
n=7 Participants
|
34 Participants
n=254 Participants
|
|
Choroidal neovascularization
Occult
|
72 Participants
n=124 Participants
|
62 Participants
n=123 Participants
|
4 Participants
n=7 Participants
|
138 Participants
n=254 Participants
|
|
Choroidal neovascularization
Unknown
|
2 Participants
n=124 Participants
|
1 Participants
n=123 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=254 Participants
|
|
Typical age-related macular degeneration
Missing
|
2 Participants
n=124 Participants
|
0 Participants
n=123 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=254 Participants
|
|
Typical age-related macular degeneration
No
|
46 Participants
n=124 Participants
|
48 Participants
n=123 Participants
|
2 Participants
n=7 Participants
|
96 Participants
n=254 Participants
|
|
Typical age-related macular degeneration
Yes
|
76 Participants
n=124 Participants
|
75 Participants
n=123 Participants
|
5 Participants
n=7 Participants
|
156 Participants
n=254 Participants
|
|
Polypoidal Choroidal Vasculopathy
Missing
|
2 Participants
n=124 Participants
|
0 Participants
n=123 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=254 Participants
|
|
Polypoidal Choroidal Vasculopathy
No
|
76 Participants
n=124 Participants
|
79 Participants
n=123 Participants
|
5 Participants
n=7 Participants
|
160 Participants
n=254 Participants
|
|
Polypoidal Choroidal Vasculopathy
Yes
|
46 Participants
n=124 Participants
|
44 Participants
n=123 Participants
|
2 Participants
n=7 Participants
|
92 Participants
n=254 Participants
|
|
Retinal Angiomatous Proliferation
Missing
|
2 Participants
n=124 Participants
|
0 Participants
n=123 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=254 Participants
|
|
Retinal Angiomatous Proliferation
No
|
118 Participants
n=124 Participants
|
114 Participants
n=123 Participants
|
6 Participants
n=7 Participants
|
238 Participants
n=254 Participants
|
|
Retinal Angiomatous Proliferation
Yes
|
4 Participants
n=124 Participants
|
9 Participants
n=123 Participants
|
1 Participants
n=7 Participants
|
14 Participants
n=254 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 52Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
Visual functions of the study eye (at every visit) and the fellow eye were assessed, according to the ETDRS protocol as described in detail in the operation manual. A higher score represents better functioning.
Outcome measures
| Measure |
2 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
|---|---|---|
|
Mean Change From Baseline in BCVA at Week 52
|
9.0 letters
Standard Deviation 14.6
|
8.4 letters
Standard Deviation 13.4
|
SECONDARY outcome
Timeframe: Week 52Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline.
Outcome measures
| Measure |
2 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
|---|---|---|
|
Percentage of Participants Who Maintained Vision at Week 52
|
96.7 percentage of participants
Interval 93.6 to 99.9
|
95.9 percentage of participants
Interval 92.4 to 99.4
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
Outcome measures
| Measure |
2 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
|---|---|---|
|
Percentage of Participants Who Gained at Least 15 Letters of Vision Compared to Baseline at Week 52
|
32.5 percentage of participants
Interval 24.2 to 40.8
|
30.9 percentage of participants
Interval 22.7 to 39.1
|
SECONDARY outcome
Timeframe: Baseline and week 52Population: The outcome measure is analyzed based on full analysis set (FAS) with number of subjects evaluable for this specific end point.
Outcome measures
| Measure |
2 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
|---|---|---|
|
Mean Change in Central Retinal Thickness (CRT) From Baseline at Week 52
|
-134.4 μm
Interval -162.2 to -106.6
|
-126.1 μm
Interval -147.1 to -105.1
|
SECONDARY outcome
Timeframe: Week 52Population: The outcome measure is analyzed based on full analysis set (FAS) including all randomized participants who received any study drug after randomization and had a baseline and at least one BCVA assessment after Week 16 (i.e. post randomization). The FAS was analyzed as randomized.
A participant was classified as without fluid if "Evidence of new or persistent fluid" on OCT was "No".
Outcome measures
| Measure |
2 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 Participants
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
|---|---|---|
|
Percentage of Participants Without Fluid on Optical Coherence Tomography (OCT) at Week 52
|
68.3 Percentage of participants
Interval 60.1 to 76.5
|
69.1 Percentage of participants
Interval 60.9 to 77.3
|
Adverse Events
2 Weeks Adjustment
Serious events: 19 serious events
Other events: 49 other events
Deaths: 0 deaths
4 Weeks Adjustment
Serious events: 20 serious events
Other events: 61 other events
Deaths: 0 deaths
Randomization Failure
Serious events: 3 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
2 Weeks Adjustment
n=124 participants at risk
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 participants at risk
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
Randomization Failure
n=7 participants at risk
Participants entered run-in phase but discontinued the study before randomization after receiving at least one injection.
|
|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Cardiac disorders
Angina unstable
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Cardiac disorders
Sinus node dysfunction
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Cataract
|
3.2%
4/124 • Up to 96 weeks
|
4.1%
5/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Age-related macular degeneration
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Gastric polyps
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Gastric mucosal lesion
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
General disorders
Vascular stent stenosis
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Hepatobiliary disorders
Cholangitis
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Hepatobiliary disorders
Cholecystitis
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.6%
2/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Infections and infestations
Cellulitis
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
28.6%
2/7 • Up to 96 weeks
|
|
Infections and infestations
Vestibular neuronitis
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Injury, poisoning and procedural complications
Snake bite
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.81%
1/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of lung
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gingival cancer
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Nervous system disorders
Spinal epidural haematoma
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.81%
1/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
Other adverse events
| Measure |
2 Weeks Adjustment
n=124 participants at risk
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
4 Weeks Adjustment
n=123 participants at risk
Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96.
|
Randomization Failure
n=7 participants at risk
Participants entered run-in phase but discontinued the study before randomization after receiving at least one injection.
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/124 • Up to 96 weeks
|
2.4%
3/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Cataract
|
4.0%
5/124 • Up to 96 weeks
|
8.1%
10/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Conjunctival haemorrhage
|
3.2%
4/124 • Up to 96 weeks
|
6.5%
8/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Dry eye
|
2.4%
3/124 • Up to 96 weeks
|
4.9%
6/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Retinal pigment epithelial tear
|
3.2%
4/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Eye disorders
Age-related macular degeneration
|
1.6%
2/124 • Up to 96 weeks
|
3.3%
4/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Constipation
|
3.2%
4/124 • Up to 96 weeks
|
5.7%
7/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Gastric ulcer
|
2.4%
3/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.81%
1/124 • Up to 96 weeks
|
2.4%
3/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Nausea
|
2.4%
3/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Toothache
|
0.81%
1/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.00%
0/124 • Up to 96 weeks
|
3.3%
4/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
General disorders
Oedema peripheral
|
0.81%
1/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Infections and infestations
Conjunctivitis
|
2.4%
3/124 • Up to 96 weeks
|
4.1%
5/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Infections and infestations
Influenza
|
1.6%
2/124 • Up to 96 weeks
|
3.3%
4/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Infections and infestations
Nasopharyngitis
|
21.0%
26/124 • Up to 96 weeks
|
16.3%
20/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
0.81%
1/124 • Up to 96 weeks
|
3.3%
4/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.81%
1/124 • Up to 96 weeks
|
2.4%
3/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/124 • Up to 96 weeks
|
2.4%
3/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/124 • Up to 96 weeks
|
0.00%
0/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.81%
1/124 • Up to 96 weeks
|
2.4%
3/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Psychiatric disorders
Insomnia
|
2.4%
3/124 • Up to 96 weeks
|
0.81%
1/123 • Up to 96 weeks
|
0.00%
0/7 • Up to 96 weeks
|
|
Vascular disorders
Hypertension
|
0.81%
1/124 • Up to 96 weeks
|
3.3%
4/123 • Up to 96 weeks
|
14.3%
1/7 • Up to 96 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place