Trial Outcomes & Findings for Efficacy and Safety of the Biosimilar Ranibizumab FYB201 in Comparison to Lucentis in Patients With Neovascular Age-related Macular Degeneration (NCT NCT02611778)

Last Updated: 2021-09-30

Results Overview

The primary endpoint was the absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 2 months (8 weeks) of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

712 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2021-09-30

Participant Flow

All 712 patients were screened for eligibility before participating in the active treatment phase of the study, resulting in 722 screenings due to 10 rescreenings. Subjects were not to be entered to trial treatment if any of the eligibility criteria were violated. Of the 712 distinct patients, 477 patients were randomized and treated.

Participant milestones

Participant milestones
Measure	FYB201 Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections
Overall Study STARTED	238	239
Overall Study COMPLETED	226	226
Overall Study NOT COMPLETED	12	13

Reasons for withdrawal

Reasons for withdrawal
Measure	FYB201 Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections
Overall Study Withdrawal by Subject	2	8
Overall Study Adverse Event	1	2
Overall Study Death	2	1
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	3	1
Overall Study Need for alternative treatment	1	0
Overall Study Other Reason	2	1

Baseline Characteristics

Efficacy and Safety of the Biosimilar Ranibizumab FYB201 in Comparison to Lucentis in Patients With Neovascular Age-related Macular Degeneration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FYB201 n=238 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=239 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=477 Participants Total of all reporting groups
Age, Continuous	74.9 years STANDARD_DEVIATION 8.26 • n=5 Participants	76.1 years STANDARD_DEVIATION 7.84 • n=7 Participants	75.5 years STANDARD_DEVIATION 8.07 • n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants	134 Participants n=7 Participants	269 Participants n=5 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	105 Participants n=7 Participants	208 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	236 Participants n=5 Participants	233 Participants n=7 Participants	469 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: FAS\_US: The FAS\_US was based on the intention to treat principle (i.e., patients were analyzed according to their randomized treatment irrespective of the treatment they actually received) and included all patients who received at least one injection of IMP, and for whom BCVA results at least after 1 month were available and who had a screening BCVA between 20/32 and 20/100 Snellen equivalent in the study eye.

The primary endpoint was the absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 2 months (8 weeks) of treatment.

Outcome measures

Outcome measures
Measure	FYB201 n=228 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=233 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=475 Participants Total of all reporting groups
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks	5.1 letters Standard Deviation 7.52	5.6 letters Standard Deviation 8.63	5.4 letters Standard Deviation 8.10

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS\_US

Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	FYB201 n=230 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=232 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=462 Participants Total of all reporting groups
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks	6.9 letters Standard Deviation 10.12	7.1 letters Standard Deviation 10.42	7.0 letters Standard Deviation 10.26

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: FAS\_US

Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 48 weeks of treatment.

Outcome measures

Outcome measures
Measure	FYB201 n=225 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=225 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=450 Participants Total of all reporting groups
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks	7.8 letters Standard Deviation 11.67	8.0 letters Standard Deviation 11.31	7.9 letters Standard Deviation 11.48

SECONDARY outcome

Timeframe: Baseline and 12 Months

Population: FAS\_US

Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 12 months, calculated as the average of the changes from baseline to Week 40, to Week 44 and to Week 48.

Outcome measures

Outcome measures
Measure	FYB201 n=228 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=227 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=455 Participants Total of all reporting groups
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months	7.8 letters Standard Deviation 11.19	7.9 letters Standard Deviation 11.01	7.8 letters Standard Deviation 11.09

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS\_US

Absolute change in Foveal Centre Point (FCP) retinal thickness \[µm\] from baseline to Week 24

Outcome measures

Outcome measures
Measure	FYB201 n=218 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=221 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=439 Participants Total of all reporting groups
Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24	-203.94 µm Standard Deviation 147.104	-205.45 µm Standard Deviation 147.199	-204.70 µm Standard Deviation 146.986

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: FAS\_US

Absolute change in Foveal Centre Point (FCP) retinal thickness \[µm\] from baseline to Week 48

Outcome measures

Outcome measures
Measure	FYB201 n=219 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=220 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=439 Participants Total of all reporting groups
Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48	-213.26 µm Standard Deviation 161.323	-211.02 µm Standard Deviation 151.950	-212.14 µm Standard Deviation 156.521

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS\_US

Absolute change in Foveal Central Subfield (FCS) retinal thickness \[µm\] from baseline to Week 24

Outcome measures

Outcome measures
Measure	FYB201 n=211 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=220 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=431 Participants Total of all reporting groups
Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24	-180.37 µm Standard Deviation 128.522	-181.63 µm Standard Deviation 126.466	-181.02 µm Standard Deviation 127.330

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: FAS\_US

Absolute change in Foveal Central Subfield (FCS) retinal thickness \[µm\] from baseline to Week 48

Outcome measures

Outcome measures
Measure	FYB201 n=207 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=213 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=420 Participants Total of all reporting groups
Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48	-182.85 µm Standard Deviation 134.588	-190.75 µm Standard Deviation 128.691	-186.86 µm Standard Deviation 131.532

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS\_US

Absolute change in total lesion area \[mm²\] from baseline to Week 24

Outcome measures

Outcome measures
Measure	FYB201 n=213 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=207 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=420 Participants Total of all reporting groups
Change in Total Lesion Area From Baseline to Week 24	-0.5742 mm² Standard Deviation 4.79222	-0.7113 mm² Standard Deviation 5.35854	-0.6418 mm² Standard Deviation 5.07361

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: FAS\_US

Absolute change in total lesion area \[mm²\] from baseline to Week 48

Outcome measures

Outcome measures
Measure	FYB201 n=163 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=166 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=329 Participants Total of all reporting groups
Change in Total Lesion Area From Baseline to Week 48	-0.6382 mm² Standard Deviation 4.81194	-1.1814 mm² Standard Deviation 5.42770	-0.9123 mm² Standard Deviation 5.13128

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS\_US

Absolute change from baseline to Week 24 in vision-related functioning and well-being measured by the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) composite score. The NEI VFQ-25 is a 25 question quality of life questionnaire with possible item scores between 0 and 100. Higher scores represent better functioning. The composite score is calculated as average over all non-missing item scores.

Outcome measures

Outcome measures
Measure	FYB201 n=228 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=230 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=458 Participants Total of all reporting groups
Change in NEI VFQ-25 Composite Score From Baseline to Week 24	3.59 score on a scale Standard Deviation 9.632	3.55 score on a scale Standard Deviation 11.237	3.57 score on a scale Standard Deviation 10.457

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: FAS\_US

Absolute change from baseline to Week 48 in vision-related functioning and well-being measured by the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) composite score. The NEI VFQ-25 is a 25 question quality of life questionnaire with possible item scores between 0 and 100. Higher scores represent better functioning. The composite score is calculated as average over all non-missing item scores.

Outcome measures

Outcome measures
Measure	FYB201 n=224 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=222 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=446 Participants Total of all reporting groups
Change in NEI VFQ-25 Composite Score From Baseline to Week 48	5.30 score on a scale Standard Deviation 12.205	3.75 score on a scale Standard Deviation 13.190	4.53 score on a scale Standard Deviation 12.714

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS\_US

Number and percentage of patients with active CNV leakage at Week 24

Outcome measures

Outcome measures
Measure	FYB201 n=221 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=219 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=440 Participants Total of all reporting groups
Active CNV Leakage at Week 24 CNV leakage	115 Participants	111 Participants	226 Participants
Active CNV Leakage at Week 24 No CNV leakage	106 Participants	108 Participants	214 Participants

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: FAS\_US

Number and percentage of patients with active CNV leakage at Week 48

Outcome measures

Outcome measures
Measure	FYB201 n=211 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=196 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=407 Participants Total of all reporting groups
Active CNV Leakage at Week 48 CNV leakage	119 Participants	115 Participants	234 Participants
Active CNV Leakage at Week 48 No CNV leakage	92 Participants	81 Participants	173 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48

Population: FAS\_US

Number and percentage of patients with fluid-free macula at each visit

Outcome measures

Outcome measures
Measure	FYB201 n=237 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=238 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=475 Participants Total of all reporting groups
Fluid-free Macula at Each Visit Week 40 · No fluid-free macula	133 Participants	115 Participants	248 Participants
Fluid-free Macula at Each Visit Baseline · Fluid-free macula	0 Participants	2 Participants	2 Participants
Fluid-free Macula at Each Visit Baseline · No fluid-free macula	236 Participants	234 Participants	470 Participants
Fluid-free Macula at Each Visit Week 4 · Fluid-free macula	43 Participants	38 Participants	81 Participants
Fluid-free Macula at Each Visit Week 4 · No fluid-free macula	187 Participants	188 Participants	375 Participants
Fluid-free Macula at Each Visit Week 8 · Fluid-free macula	69 Participants	62 Participants	131 Participants
Fluid-free Macula at Each Visit Week 8 · No fluid-free macula	154 Participants	168 Participants	322 Participants
Fluid-free Macula at Each Visit Week 12 · Fluid-free macula	86 Participants	76 Participants	162 Participants
Fluid-free Macula at Each Visit Week 12 · No fluid-free macula	141 Participants	155 Participants	296 Participants
Fluid-free Macula at Each Visit Week 16 · Fluid-free macula	87 Participants	87 Participants	174 Participants
Fluid-free Macula at Each Visit Week 16 · No fluid-free macula	136 Participants	149 Participants	285 Participants
Fluid-free Macula at Each Visit Week 20 · Fluid-free macula	80 Participants	97 Participants	177 Participants
Fluid-free Macula at Each Visit Week 20 · No fluid-free macula	146 Participants	137 Participants	283 Participants
Fluid-free Macula at Each Visit Week 24 · Fluid-free macula	86 Participants	100 Participants	186 Participants
Fluid-free Macula at Each Visit Week 24 · No fluid-free macula	141 Participants	131 Participants	272 Participants
Fluid-free Macula at Each Visit Week 28 · Fluid-free macula	86 Participants	98 Participants	184 Participants
Fluid-free Macula at Each Visit Week 28 · No fluid-free macula	140 Participants	121 Participants	261 Participants
Fluid-free Macula at Each Visit Week 32 · Fluid-free macula	91 Participants	96 Participants	187 Participants
Fluid-free Macula at Each Visit Week 32 · No fluid-free macula	131 Participants	125 Participants	256 Participants
Fluid-free Macula at Each Visit Week 36 · Fluid-free macula	83 Participants	99 Participants	182 Participants
Fluid-free Macula at Each Visit Week 36 · No fluid-free macula	142 Participants	119 Participants	261 Participants
Fluid-free Macula at Each Visit Week 40 · Fluid-free macula	87 Participants	102 Participants	189 Participants
Fluid-free Macula at Each Visit Week 44 · Fluid-free macula	92 Participants	104 Participants	196 Participants
Fluid-free Macula at Each Visit Week 44 · No fluid-free macula	129 Participants	116 Participants	245 Participants
Fluid-free Macula at Each Visit Week 48 · Fluid-free macula	105 Participants	108 Participants	213 Participants
Fluid-free Macula at Each Visit Week 48 · No fluid-free macula	120 Participants	113 Participants	233 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 4, 12, 24, 48

Population: SAF

Frequency of patients with anti-drug antibodies (ADAs) by scheduled eCRF visit

Outcome measures

Outcome measures
Measure	FYB201 n=238 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=239 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=477 Participants Total of all reporting groups
Anti-drug Antibodies by Scheduled eCRF Visit Baseline · Positive anti-drug antibodies	0 Participants	5 Participants	5 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Baseline · Negative anti-drug antibodies	234 Participants	233 Participants	467 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 1 · Positive anti-drug antibodies	0 Participants	0 Participants	0 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 1 · Negative anti-drug antibodies	28 Participants	29 Participants	57 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 4 · Positive anti-drug antibodies	2 Participants	2 Participants	4 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 4 · Negative anti-drug antibodies	224 Participants	226 Participants	450 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 12 · Positive anti-drug antibodies	1 Participants	2 Participants	3 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 12 · Negative anti-drug antibodies	225 Participants	224 Participants	449 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 24 · Positive anti-drug antibodies	6 Participants	6 Participants	12 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 24 · Negative anti-drug antibodies	219 Participants	219 Participants	438 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 48 · Positive anti-drug antibodies	9 Participants	12 Participants	21 Participants
Anti-drug Antibodies by Scheduled eCRF Visit Week 48 · Negative anti-drug antibodies	220 Participants	213 Participants	433 Participants

SECONDARY outcome

Timeframe: Baseline and up to Week 48

Population: SAF

Number and percentage of patients with detection of anti-drug antibodies (ADAs) pre-first dosing and post-first dosing (combination of all ADA assessments after first injection of study medication).

Outcome measures

Outcome measures
Measure	FYB201 n=238 Participants Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=239 Participants Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Total n=477 Participants Total of all reporting groups
Anti-drug Antibodies Pre- and Post-first Dosing Post-first dosing · Positive anti-drug antibodies	14 Participants	14 Participants	28 Participants
Anti-drug Antibodies Pre- and Post-first Dosing Pre-first dosing · Positive anti-drug antibodies	0 Participants	5 Participants	5 Participants
Anti-drug Antibodies Pre- and Post-first Dosing Pre-first dosing · Negative anti-drug antibodies	232 Participants	231 Participants	463 Participants
Anti-drug Antibodies Pre- and Post-first Dosing Post-first dosing · Negative anti-drug antibodies	223 Participants	224 Participants	447 Participants

Adverse Events

FYB201

Serious events: 19 serious events

Other events: 149 other events

Deaths: 2 deaths

Lucentis

Serious events: 32 serious events

Other events: 161 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Development

bioeq GmbH

Phone: +498024463330

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	FYB201 n=238 participants at risk Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections	Lucentis n=239 participants at risk Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections
Eye disorders Cataract	0.42% 1/238 • Number of events 1 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	4.2% 10/239 • Number of events 13 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Choroidal neovascularisation	2.5% 6/238 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	1.7% 4/239 • Number of events 4 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Conjunctival haemorrhage	5.9% 14/238 • Number of events 24 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	7.9% 19/239 • Number of events 30 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Conjunctival hyperaemia	1.7% 4/238 • Number of events 4 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.5% 6/239 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Eye pain	3.8% 9/238 • Number of events 14 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.5% 6/239 • Number of events 8 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Lacrimation increased	3.8% 9/238 • Number of events 11 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	0.84% 2/239 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Neovascular age-related macular degeneration	8.0% 19/238 • Number of events 19 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	9.2% 22/239 • Number of events 24 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Punctate keratitis	3.4% 8/238 • Number of events 15 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	5.0% 12/239 • Number of events 25 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Retinal haemorrhage	2.9% 7/238 • Number of events 9 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	1.3% 3/239 • Number of events 3 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Retinal pigment epithelial tear	0.84% 2/238 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.5% 6/239 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Visual acuity reduced	2.5% 6/238 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	4.6% 11/239 • Number of events 13 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Vitreous detachment	2.5% 6/238 • Number of events 7 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	1.7% 4/239 • Number of events 4 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Eye disorders Vitreous floaters	1.3% 3/238 • Number of events 3 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Gastrointestinal disorders Diarrhoea	0.84% 2/238 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
General disorders Pain	2.1% 5/238 • Number of events 9 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	0.84% 2/239 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Infections and infestations Bronchitis	3.4% 8/238 • Number of events 8 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Infections and infestations Conjunctivitis	3.8% 9/238 • Number of events 10 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	0.84% 2/239 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Infections and infestations Influenza	2.1% 5/238 • Number of events 7 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	0.84% 2/239 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Infections and infestations Nasopharyngitis	5.0% 12/238 • Number of events 15 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	6.7% 16/239 • Number of events 17 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Infections and infestations Upper respiratory tract infection	3.4% 8/238 • Number of events 10 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.5% 6/239 • Number of events 7 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Infections and infestations Urinary tract infection	1.3% 3/238 • Number of events 3 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.5% 6/239 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Injury, poisoning and procedural complications Fall	0.84% 2/238 • Number of events 2 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Investigations Blood urea increased	1.7% 4/238 • Number of events 4 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Investigations C-reactive protein increased	4.2% 10/238 • Number of events 11 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Investigations Intraocular pressure increased	4.6% 11/238 • Number of events 20 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	5.0% 12/239 • Number of events 15 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Investigations Visual acuity tests abnormal	1.7% 4/238 • Number of events 4 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/238 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Musculoskeletal and connective tissue disorders Back pain	2.1% 5/238 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	3.3% 8/239 • Number of events 8 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Nervous system disorders Dizziness	0.42% 1/238 • Number of events 1 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Nervous system disorders Headache	1.7% 4/238 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	3.3% 8/239 • Number of events 9 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Respiratory, thoracic and mediastinal disorders Cough	2.1% 5/238 • Number of events 7 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	2.1% 5/239 • Number of events 5 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF
Vascular disorders Hypertension	1.3% 3/238 • Number of events 6 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF	5.9% 14/239 • Number of events 25 • From first treatment up to Week 48 All Adverse Events are reported in this record from First Patient First Treatment until Last Patient Last Visit. SAF