Trial Outcomes & Findings for Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR) (NCT NCT02718326)

Last Updated: 2020-07-30

Results Overview

The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 24 from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

402 participants

Primary outcome timeframe

At Week 24

Results posted on

2020-07-30

Participant Flow

Recruitment for this study was conducted in the following countries between 29 Mar 2016 and 07 Aug 2017: Germany, Hungary, Japan, the United Kingdom, and the United States. A total of 759 participants were screened.

Out of 759, 402 participants were randomized to receive 1 of 3 treatment groups in a 1:1:1 ratio stratified based on their Diabetic Retinopathy Severity Scale (DRSS) score (level 47 vs. level 53). Only 1 eye was selected as the study eye.

Unit of analysis: Eyes

Participant milestones

Participant milestones
Measure	Sham Treatment All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Study STARTED	133 133	135 135	134 134
Overall Study Completed Week 52	109 109	122 122	124 124
Overall Study COMPLETED	97 97	111 111	112 112
Overall Study NOT COMPLETED	36 36	24 24	22 22

Reasons for withdrawal

Reasons for withdrawal
Measure	Sham Treatment All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Study Adverse Event	4	9	0
Overall Study Death	8	1	2
Overall Study Withdrawal by Subject	4	9	6
Overall Study Lost to Follow-up	18	5	14
Overall Study Protocol Deviation	1	0	0
Overall Study Pregnancy	1	0	0

Baseline Characteristics

Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	Total n=402 Participants Total of all reporting groups
Age, Continuous	55.8 Years STANDARD_DEVIATION 10.31 • n=5 Participants	55.4 Years STANDARD_DEVIATION 11.13 • n=7 Participants	55.8 Years STANDARD_DEVIATION 10.19 • n=5 Participants	55.7 Years STANDARD_DEVIATION 10.53 • n=4 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	60 Participants n=7 Participants	53 Participants n=5 Participants	177 Participants n=4 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	75 Participants n=7 Participants	81 Participants n=5 Participants	225 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	74 Participants n=5 Participants	97 Participants n=7 Participants	93 Participants n=5 Participants	264 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants	37 Participants n=7 Participants	41 Participants n=5 Participants	136 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	12 Participants n=7 Participants	7 Participants n=5 Participants	23 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	41 Participants n=4 Participants
Race (NIH/OMB) White	107 Participants n=5 Participants	99 Participants n=7 Participants	104 Participants n=5 Participants	310 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants
Baseline Diabetic Retinopathy Severity Score (DRSS) Level 47 (Moderately Severe)	99 Participants n=5 Participants	102 Participants n=7 Participants	101 Participants n=5 Participants	302 Participants n=4 Participants
Baseline Diabetic Retinopathy Severity Score (DRSS) Level 53 (Severe)	34 Participants n=5 Participants	33 Participants n=7 Participants	33 Participants n=5 Participants	100 Participants n=4 Participants

PRIMARY outcome

Timeframe: At Week 24

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). The missing data were imputed using last observation carried forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) n=269 Participants IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Percentage of Participants Who Improved by ≥2 Steps From Baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at Week 24 in the Combined 2Q16 and 2Q8 Groups	6.0 Percentage of participants	61.5 Percentage of participants	55.2 Percentage of participants	58.4 Percentage of participants

PRIMARY outcome

Timeframe: At Week 52

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). The missing data were imputed using LOCF method.

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline	15.0 Percentage of participants	65.2 Percentage of participants	79.9 Percentage of participants	—

SECONDARY outcome

Timeframe: At Week 52

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

Vision-threatening complications are defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris \[at least 2 cumulative clock hours\], and/or definitive neovascularization of the iridocorneal angle).

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52	20.3 Percentage of participants	3.7 Percentage of participants	3.0 Percentage of participants	—

SECONDARY outcome

Timeframe: At Week 52

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

The percentage of participants who developed CI-DME at week 52 were reported.

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52	25.6 Percentage of participants	6.7 Percentage of participants	8.2 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline through week 52 (day 365)

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). Participants who did not have an event were censored at their last visit at or before the week 52 visit. Here, the value "NA" = Not evaluable due to small number of VTC events.

Vision-threatening complication (VTC) is defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris \[at least 2 cumulative clock hours\], and/or definitive neovascularization of the iridocorneal angle). Vision Threatening Complications include PDR/ASNV identified by investigators and Diabetic Retinopathy Scale Score (DRSS) \>61.

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52	NA Days Interval 371.0 to NA = Not evaluable due to small number of VTC events	NA Days NA = Not evaluable due to small number of VTC events	NA Days NA = Not evaluable due to small number of VTC events	—

SECONDARY outcome

Timeframe: Baseline through week 52 (day 365)

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). Participants who did not have an event were censored at their last visit, at or before the week 52 visit. Here, the value "NA" = Not evaluable due to small number of CI-DME events.

Time to develop Central Involved-Diabetic Macular Edema (CI-DME) through week 52 reported.

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52	NA Days Interval 333.0 to NA = Not evaluable due to small number of CI-DME events	NA Days NA = Not evaluable due to small number of CI-DME events	NA Days NA = Not evaluable due to small number of CI-DME events	—

SECONDARY outcome

Timeframe: At Week 52

Population: FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

The percentage of participants who received panretinal photocoagulation (PRP), inclusive of participants undergoing vitrectomy with endolaser, at week 52 were reported.

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52	6.8 Percentage of participants	0.7 Percentage of participants	0.7 Percentage of participants	—

SECONDARY outcome

Timeframe: At week 52

Population: AUC was calculated as a weighted average based on total AUC (using the trapezoidal rule) divided by total duration in days. FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

The area under the curve (AUC) is the area under the best corrected visual acuity (BCVA) versus time curve from baseline to week 52. Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).

Outcome measures

Outcome measures
Measure	Sham Treatment n=133 Participants All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 Participants All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 Participants All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52	0.5 scores on a scale Standard Deviation 3.01	1.7 scores on a scale Standard Deviation 3.50	1.3 scores on a scale Standard Deviation 3.49	—

Adverse Events

Sham Treatment

Serious events: 38 serious events

Other events: 104 other events

Deaths: 8 deaths

Intravitreal Aflibercept Injection (IAI) 2Q16

Serious events: 38 serious events

Other events: 104 other events

Deaths: 1 deaths

Intravitreal Aflibercept Injection (IAI) 2Q8

Serious events: 47 serious events

Other events: 106 other events

Deaths: 3 deaths

IAI 2 mg Groups Combined (2Q16 & 2Q8)

Serious events: 85 serious events

Other events: 210 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Management

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Sham Treatment n=133 participants at risk All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 participants at risk All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 participants at risk All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) n=269 participants at risk IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Cardiac disorders Cardiac failure	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Coronary artery disease	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.0% 4/134 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.3% 9/269 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Cardiac failure congestive	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/134 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.9% 5/269 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Myocardial infarction	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.1% 3/269 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Acute myocardial infarction	1.5% 2/133 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 2/269 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Cardiac failure acute	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 2/269 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Coronary artery stenosis	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 2/269 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Atrial fibrillation	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Atrial flutter	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Cardiac arrest	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Cardiac failure chronic	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Myocardial ischaemia	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Supraventricular tachycardia	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Acute coronary syndrome	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Ischaemic cardiomyopathy	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Left ventricular dysfunction	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Left ventricular failure	1.5% 2/133 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Cardiac disorders Pulseless electrical activity	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Cellulitis	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/134 • Number of events 6 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.6% 7/269 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Pneumonia	1.5% 2/133 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/135 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/134 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 6/269 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Diabetic foot infection	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/135 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.1% 3/269 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Sepsis	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/134 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.1% 3/269 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Abscess limb	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/134 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 2/269 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Arthritis bacterial	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Enterococcal bacteraemia	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Gastroenteritis viral	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Influenza	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Osteomyelitis	3.0% 4/133 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Osteomyelitis acute	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Pneumonia bacterial	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Sepsis syndrome	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Staphylococcal infection	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Staphylococcal osteomyelitis	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Staphylococcal skin infection	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Urinary tract infection	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.74% 1/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Appendicitis	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Diabetic gangrene	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Infected skin ulcer	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Septic shock	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/134 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/269 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Injury, poisoning and procedural complications Anaemia postoperative	0.00% 0/133 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.00% 0/135 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.75% 1/134 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	0.37% 1/269 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).

Other adverse events
Measure	Sham Treatment n=133 participants at risk All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q16 n=135 participants at risk All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	Intravitreal Aflibercept Injection (IAI) 2Q8 n=134 participants at risk All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	IAI 2 mg Groups Combined (2Q16 & 2Q8) n=269 participants at risk IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Gastrointestinal disorders Constipation	2.3% 3/133 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/134 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.5% 12/269 • Number of events 12 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Gastrointestinal disorders Nausea	6.0% 8/133 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.5% 6/134 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.1% 11/269 • Number of events 19 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Bronchitis	5.3% 7/133 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.7% 9/135 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/134 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 14/269 • Number of events 15 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Cellulitis	4.5% 6/133 • Number of events 6 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/134 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.5% 12/269 • Number of events 17 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Influenza	6.0% 8/133 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	7.4% 10/135 • Number of events 12 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.0% 4/134 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 14/269 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Nasopharyngitis	11.3% 15/133 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.1% 11/135 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.2% 11/134 • Number of events 12 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.2% 22/269 • Number of events 28 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Infections and infestations Urinary tract infection	12.0% 16/133 • Number of events 22 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.9% 12/135 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.2% 11/134 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.6% 23/269 • Number of events 26 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Injury, poisoning and procedural complications Fall	3.8% 5/133 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.0% 8/134 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.8% 13/269 • Number of events 18 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Investigations Blood glucose increased	5.3% 7/133 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/135 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/134 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 10/269 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Investigations Glycosylated haemoglobin increased	5.3% 7/133 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.7% 9/135 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.7% 9/134 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.7% 18/269 • Number of events 18 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Metabolism and nutrition disorders Diabetes mellitus	9.8% 13/133 • Number of events 15 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.1% 11/135 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.0% 8/134 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	7.1% 19/269 • Number of events 19 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Nervous system disorders Headache	1.5% 2/133 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/135 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.0% 8/134 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.6% 15/269 • Number of events 17 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Vascular disorders Hypertension	18.8% 25/133 • Number of events 28 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	20.7% 28/135 • Number of events 32 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	14.9% 20/134 • Number of events 23 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	17.8% 48/269 • Number of events 55 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Blepharitis Fellow Eye	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/135 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/134 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 10/269 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Cataract Fellow Eye	3.0% 4/133 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.7% 9/135 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.0% 4/134 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.8% 13/269 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Conjunctival haemorrhage Fellow Eye	4.5% 6/133 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.0% 8/134 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.8% 13/269 • Number of events 28 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Diabetic retinal oedema Fellow Eye	14.3% 19/133 • Number of events 25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	12.6% 17/135 • Number of events 24 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	17.2% 23/134 • Number of events 27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	14.9% 40/269 • Number of events 51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Diabetic retinopathy Fellow Eye	9.0% 12/133 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	9.6% 13/135 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	7.5% 10/134 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.6% 23/269 • Number of events 24 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Macular oedema Fellow Eye	3.0% 4/133 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/135 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.5% 6/134 • Number of events 6 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.8% 13/269 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Retinal exudates Fellow Eye	6.0% 8/133 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.5% 6/134 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.0% 8/269 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Vitreous haemorrhage Fellow Eye	3.0% 4/133 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.9% 8/135 • Number of events 12 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/134 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	4.1% 11/269 • Number of events 15 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Blepharitis Study Eye	0.75% 1/133 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	1.5% 2/135 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/134 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.3% 9/269 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Cataract Study Eye	3.8% 5/133 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.9% 8/135 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.0% 8/134 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.9% 16/269 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Conjunctival haemorrhage Study Eye	6.0% 8/133 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	13.3% 18/135 • Number of events 27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	18.7% 25/134 • Number of events 34 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	16.0% 43/269 • Number of events 61 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Diabetic retinal oedema Study Eye	32.3% 43/133 • Number of events 54 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	10.4% 14/135 • Number of events 22 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	14.2% 19/134 • Number of events 25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	12.3% 33/269 • Number of events 47 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Diabetic retinopathy Study Eye	16.5% 22/133 • Number of events 25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	2.2% 3/135 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/134 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.0% 8/269 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Eye pain Study Eye	4.5% 6/133 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	8.1% 11/135 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/134 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.9% 16/269 • Number of events 18 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Retinal exudates Study Eye	4.5% 6/133 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	3.7% 5/135 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	6.7% 9/134 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 14/269 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Vitreous detachment Study Eye	3.0% 4/133 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/135 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/134 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 14/269 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
Eye disorders Vitreous floaters Study Eye	2.3% 3/133 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	5.2% 7/135 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	9.7% 13/134 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).	7.4% 20/269 • Number of events 21 • All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).