Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO) (NCT NCT04592419)

Last Updated: 2024-06-26

Results Overview

BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

568 participants

Primary outcome timeframe

Day 1 to Week 24

Results posted on

2024-06-26

Participant Flow

Participants were recruited based on physician referral at 138 medical centers between September 2020 and December 2021. The first participant was enrolled on 25 September 2020 and the last on 15 December 2021.

Of 752 enrolled participants, 568 met eligibility criteria and were randomized to treatment.

Participant milestones

Participant milestones
Measure	KSI-301 (Arm A) Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Primary Study (Through Year 1) STARTED	284	284
Primary Study (Through Year 1) Completed Treatment at Week 20	270	274
Primary Study (Through Year 1) Did Not Discontinue Treatment Before Week 24	270	276
Primary Study (Through Year 1) Did Not Discontinue Study Before Week 24	275	276
Primary Study (Through Year 1) COMPLETED	255	255
Primary Study (Through Year 1) NOT COMPLETED	29	29
Open-Label Extension Period STARTED	216	228
Open-Label Extension Period COMPLETED	135	130
Open-Label Extension Period NOT COMPLETED	81	98

Reasons for withdrawal

Reasons for withdrawal
Measure	KSI-301 (Arm A) Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Primary Study (Through Year 1) Adverse Event	10	3
Primary Study (Through Year 1) Non-compliance with Study Schedule	0	1
Primary Study (Through Year 1) Withdrawal by Subject	7	13
Primary Study (Through Year 1) Lost to Follow-up	5	5
Primary Study (Through Year 1) Progressive Disease	1	1
Primary Study (Through Year 1) Sponsor Request	4	5
Primary Study (Through Year 1) Participant left the country	2	0
Primary Study (Through Year 1) Participant moved to another city with no available site	0	1
Open-Label Extension Period Adverse Event	1	2
Open-Label Extension Period Non-compliance with Study Schedule	1	0
Open-Label Extension Period Withdrawal by Subject	5	7
Open-Label Extension Period Lost to Follow-up	1	5
Open-Label Extension Period Sponsor Request	73	84

Baseline Characteristics

A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Total n=568 Participants Total of all reporting groups
Age, Customized 18-64 years	126 Participants n=99 Participants	142 Participants n=107 Participants	268 Participants n=206 Participants
Age, Customized 65-74 years	94 Participants n=99 Participants	86 Participants n=107 Participants	180 Participants n=206 Participants
Age, Customized 75-84 years	50 Participants n=99 Participants	41 Participants n=107 Participants	91 Participants n=206 Participants
Age, Customized ≥ 85 years	14 Participants n=99 Participants	15 Participants n=107 Participants	29 Participants n=206 Participants
Sex: Female, Male Female	141 Participants n=99 Participants	138 Participants n=107 Participants	279 Participants n=206 Participants
Sex: Female, Male Male	143 Participants n=99 Participants	146 Participants n=107 Participants	289 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	5 Participants n=99 Participants	5 Participants n=107 Participants	10 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	23 Participants n=99 Participants	17 Participants n=107 Participants	40 Participants n=206 Participants
Race (NIH/OMB) White	240 Participants n=99 Participants	245 Participants n=107 Participants	485 Participants n=206 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=99 Participants	14 Participants n=107 Participants	29 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	31 Participants n=99 Participants	29 Participants n=107 Participants	60 Participants n=206 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	242 Participants n=99 Participants	246 Participants n=107 Participants	488 Participants n=206 Participants
Race/Ethnicity, Customized Choose Not to Respond	11 Participants n=99 Participants	9 Participants n=107 Participants	20 Participants n=206 Participants
Geographic Region North America	193 Participants n=99 Participants	193 Participants n=107 Participants	386 Participants n=206 Participants
Geographic Region Rest of World	91 Participants n=99 Participants	91 Participants n=107 Participants	182 Participants n=206 Participants
Blood Pressure at Baseline Systolic	139.1 mmHG STANDARD_DEVIATION 16.66 • n=99 Participants	138.7 mmHG STANDARD_DEVIATION 16.42 • n=107 Participants	138.9 mmHG STANDARD_DEVIATION 16.52 • n=206 Participants
Blood Pressure at Baseline Diastolic	82.8 mmHG STANDARD_DEVIATION 8.71 • n=99 Participants	82.6 mmHG STANDARD_DEVIATION 9.33 • n=107 Participants	82.7 mmHG STANDARD_DEVIATION 9.02 • n=206 Participants

PRIMARY outcome

Timeframe: Day 1 to Week 24

Population: Full Analysis Set (Week 24) includes all randomized participants who received at least one treatment injection in the first 24 weeks and using all available post baseline measurements up to Week 24 or until the participant discontinues study treatment.

BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=220 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=218 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.	14.2 ETDRS Letters Standard Error .81	15.6 ETDRS Letters Standard Error .79

PRIMARY outcome

Timeframe: Day 1 to Week 24

Population: Full Analysis Set (Week 24) includes all randomized subjects who received at least one treatment injection in the first 24 weeks and using all available post baseline measurements up to Week 24 or until the subject discontinues study treatment.

BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.	13.0 ETDRS Letters Standard Error .83	15.5 ETDRS Letters Standard Error .81

SECONDARY outcome

Timeframe: Day 1 - Week 48

Population: Full Analysis Set (Week 24 or 48) includes all randomized participants who received at least one treatment injection in the first 24/48 weeks and using all available post baseline measurements up to Week 24/48 or until the participant discontinues study treatment. Number analyzed by visit is equal to the number of participants who had data available at that respective visit.

BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 1	7.7 ETDRS Letters Standard Deviation 9.25	7.9 ETDRS Letters Standard Deviation 7.74
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 4	8.9 ETDRS Letters Standard Deviation 9.89	11.2 ETDRS Letters Standard Deviation 10.01
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 8	11.4 ETDRS Letters Standard Deviation 10.38	13.5 ETDRS Letters Standard Deviation 9.78
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 12	10.0 ETDRS Letters Standard Deviation 12.58	14.2 ETDRS Letters Standard Deviation 10.05
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 16	12.7 ETDRS Letters Standard Deviation 11.99	14.9 ETDRS Letters Standard Deviation 10.52
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 20	12.4 ETDRS Letters Standard Deviation 12.29	15.3 ETDRS Letters Standard Deviation 11.86
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 24	14.0 ETDRS Letters Standard Deviation 11.42	15.6 ETDRS Letters Standard Deviation 11.54
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 36	13.1 ETDRS Letters Standard Deviation 11.52	13.5 ETDRS Letters Standard Deviation 11.96
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 40	13.9 ETDRS Letters Standard Deviation 11.51	13.9 ETDRS Letters Standard Deviation 12.87
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 44	13.6 ETDRS Letters Standard Deviation 11.26	13.7 ETDRS Letters Standard Deviation 13.11
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 48	13.5 ETDRS Letters Standard Deviation 12.10	14.2 ETDRS Letters Standard Deviation 13.64
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 28	12.8 ETDRS Letters Standard Deviation 11.85	14.1 ETDRS Letters Standard Deviation 12.90
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Week 32	13.3 ETDRS Letters Standard Deviation 11.55	13.8 ETDRS Letters Standard Deviation 12.46

SECONDARY outcome

Timeframe: Day 1 - Week 48

Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100\*n/N.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 1.	176 Participants	176 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 4.	197 Participants	202 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 8.	211 Participants	233 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 12.	198 Participants	237 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 16.	222 Participants	240 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 20.	199 Participants	235 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 24.	215 Participants	233 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 28.	206 Participants	211 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 32.	200 Participants	213 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 36.	205 Participants	212 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 40.	210 Participants	215 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 44.	196 Participants	211 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 5 letters from baseline to Week 48.	199 Participants	206 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 1.	94 Participants	91 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 4.	120 Participants	145 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 8.	151 Participants	175 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 12.	141 Participants	179 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 16.	168 Participants	181 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 20.	168 Participants	183 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 24.	177 Participants	188 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 28.	160 Participants	168 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 32.	164 Participants	172 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 36.	158 Participants	162 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 40.	167 Participants	162 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 44.	156 Participants	164 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 10 letters from baseline to Week 48.	159 Participants	164 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 1.	46 Participants	49 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 4.	69 Participants	85 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 8.	92 Participants	111 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 12.	83 Participants	119 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 16.	109 Participants	131 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 20.	109 Participants	137 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 24.	121 Participants	138 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 28.	111 Participants	118 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 32.	113 Participants	113 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 40.	107 Participants	120 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 44.	111 Participants	116 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 48.	112 Participants	120 Participants
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Participants who gain ≥ 15 letters from baseline to Week 36.	108 Participants	112 Participants

SECONDARY outcome

Timeframe: Day 1 - Week 48

Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100\*n/N.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 1.	5 Participants	6 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 4.	19 Participants	7 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 8.	14 Participants	3 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 12.	18 Participants	3 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 16.	13 Participants	5 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 20.	17 Participants	8 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 24.	13 Participants	7 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 28.	16 Participants	10 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 32.	14 Participants	9 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 36.	16 Participants	11 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 40.	13 Participants	14 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 44.	10 Participants	15 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 5 letters from baseline to Week 48.	18 Participants	15 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 1.	3 Participants	1 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 4.	4 Participants	1 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 8.	6 Participants	1 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 12.	9 Participants	0 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 16.	6 Participants	2 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 20.	10 Participants	5 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 24.	4 Participants	4 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 28.	9 Participants	8 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 32.	9 Participants	7 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 36.	10 Participants	4 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 40.	9 Participants	8 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 44.	6 Participants	9 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 10 letters from baseline to Week 48.	9 Participants	9 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 1.	2 Participants	0 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 4.	2 Participants	1 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participant who lose ≥ 15 letters from baseline to Week 8.	1 Participants	0 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 12.	6 Participants	0 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 16.	5 Participants	1 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 20.	4 Participants	2 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 24.	1 Participants	2 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 28.	5 Participants	5 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 32.	4 Participants	6 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 36.	2 Participants	2 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 40.	3 Participants	5 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 44.	3 Participants	6 Participants
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Participants who lose ≥ 15 letters from baseline to Week 48.	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Day 1 - Week 48.

Percentage of participants with BCVA Snellen Equivalent of 20/40 or Better from Baseline to Week 48. Snellen Equivalent of 20/40 is 69 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100\*n/N.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Baseline.	92 Participants	90 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 1.	168 Participants	153 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 4.	173 Participants	182 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 8.	185 Participants	198 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 12.	186 Participants	199 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 20.	189 Participants	207 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 24.	196 Participants	205 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 28.	192 Participants	197 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 32.	182 Participants	190 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 36.	188 Participants	192 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 40.	191 Participants	193 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 44.	184 Participants	191 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 48.	182 Participants	190 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Snellen equivalent of 20/40 or better at Week 16.	200 Participants	209 Participants

SECONDARY outcome

Timeframe: Baseline - Week 48

Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse from Baseline to Week 48. Snellen Equivalent of 20/200 is 38 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100\*n/N.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Baseline	22 Participants	31 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 1	9 Participants	12 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 4	10 Participants	9 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 8	6 Participants	5 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 12	11 Participants	4 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 16	7 Participants	7 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 20	7 Participants	5 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 24	2 Participants	4 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 28	5 Participants	6 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 32	3 Participants	5 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 36	2 Participants	3 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 40	2 Participants	7 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 44	2 Participants	6 Participants
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Snellen Equivalent of 20/200 or Worse at Week 48	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline - Week 48

Macular Edema (ME) is assessed by optical coherence tomography (OCT) central subfield thickness (CST). A thickness of less than 325 microns is considered absence of ME. Proportion of participants with Absence of Macular Edema from Baseline to Week 48. Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100\*n/N.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 16	218 Participants	245 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 20	174 Participants	240 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 24	221 Participants	247 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 28	185 Participants	196 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 32	168 Participants	173 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 36	172 Participants	172 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 40	179 Participants	188 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 44	160 Participants	177 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 48	166 Participants	187 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Baseline	4 Participants	7 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 1	156 Participants	150 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 4	174 Participants	225 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 8	205 Participants	247 Participants
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Absence of Macular Edema at Week 12	160 Participants	252 Participants

SECONDARY outcome

Timeframe: Day 1 - Week 48

Mean change in OCT central subfield retinal thickness (CST) from baseline by visit over time (up to Week 48) for all RVO participants.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 1	-225.2 micrometers (um) Standard Deviation 152.87	-255.9 micrometers (um) Standard Deviation 168.25
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 4	-230.8 micrometers (um) Standard Deviation 181.37	-294.2 micrometers (um) Standard Deviation 195.07
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 8	-255.6 micrometers (um) Standard Deviation 190.40	-310.1 micrometers (um) Standard Deviation 203.17
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 12	-195.8 micrometers (um) Standard Deviation 213.70	-314.8 micrometers (um) Standard Deviation 208.68
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 16	-264.9 micrometers (um) Standard Deviation 204.77	-321.0 micrometers (um) Standard Deviation 209.84
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 20	-218.1 micrometers (um) Standard Deviation 203.88	-323.0 micrometers (um) Standard Deviation 209.89
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 24	-278.9 micrometers (um) Standard Deviation 192.68	-326.6 micrometers (um) Standard Deviation 210.78
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 28	-240.4 micrometers (um) Standard Deviation 200.78	-273.9 micrometers (um) Standard Deviation 218.56
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 32	-246.6 micrometers (um) Standard Deviation 200.99	-269.7 micrometers (um) Standard Deviation 213.89
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 36	-243.4 micrometers (um) Standard Deviation 198.13	-258.6 micrometers (um) Standard Deviation 213.44
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 40	-246.9 micrometers (um) Standard Deviation 193.79	-274.9 micrometers (um) Standard Deviation 229.38
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 44	-237.5 micrometers (um) Standard Deviation 189.30	-258.3 micrometers (um) Standard Deviation 216.49
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Week 48	-240.0 micrometers (um) Standard Deviation 203.97	-278.8 micrometers (um) Standard Deviation 224.13

SECONDARY outcome

Timeframe: Day 1 - Week 48

Mean change in OCT center point retinal thickness (CPT) from baseline by visit over time (up to Week 48) for all RVO participants.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=284 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 1	-278.7 micrometers (um) Standard Deviation 186.23	-320.9 micrometers (um) Standard Deviation 200.00
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 4	-278.5 micrometers (um) Standard Deviation 212.92	-358.4 micrometers (um) Standard Deviation 224.51
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 8	-301.4 micrometers (um) Standard Deviation 220.72	-373.9 micrometers (um) Standard Deviation 235.35
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 12	-230.3 micrometers (um) Standard Deviation 248.92	-377.6 micrometers (um) Standard Deviation 239.01
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 16	-311.5 micrometers (um) Standard Deviation 237.01	-381.3 micrometers (um) Standard Deviation 240.74
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 20	-258.1 micrometers (um) Standard Deviation 236.58	-385.4 micrometers (um) Standard Deviation 238.61
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 24	-327.9 micrometers (um) Standard Deviation 223.13	-387.5 micrometers (um) Standard Deviation 240.42
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 28	-280.5 micrometers (um) Standard Deviation 232.22	-328.0 micrometers (um) Standard Deviation 249.96
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 32	-288.9 micrometers (um) Standard Deviation 229.6	-322.4 micrometers (um) Standard Deviation 244.98
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 36	-286.8 micrometers (um) Standard Deviation 229.63	-308.1 micrometers (um) Standard Deviation 247.22
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 40	-290.7 micrometers (um) Standard Deviation 220.56	-328.7 micrometers (um) Standard Deviation 261.26
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 44	-281.5 micrometers (um) Standard Deviation 221.38	-306.6 micrometers (um) Standard Deviation 252.79
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Week 48	-279.6 micrometers (um) Standard Deviation 231.43	-331.6 micrometers (um) Standard Deviation 259.43

Adverse Events

KSI-301 (Arm A)

Serious events: 36 serious events

Other events: 73 other events

Deaths: 3 deaths

Aflibercept (Arm B)

Serious events: 23 serious events

Other events: 66 other events

Deaths: 1 deaths

KSI-301 5mg Extension Phase

Serious events: 18 serious events

Other events: 53 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	KSI-301 (Arm A) n=284 participants at risk Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. KSI-301: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	Aflibercept (Arm B) n=284 participants at risk Intravitreal injection of aflibercept (2 mg) once every 4 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.	KSI-301 5mg Extension Phase n=444 participants at risk In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.
Eye disorders Conjunctival haemorrhage - Study eye	8.5% 24/284 • Number of events 27 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.	7.7% 22/284 • Number of events 24 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.	1.8% 8/444 • Number of events 8 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.
Infections and infestations COVID-19	10.6% 30/284 • Number of events 30 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.	8.1% 23/284 • Number of events 23 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.	7.2% 32/444 • Number of events 33 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.
Vascular disorders Hypertension	10.6% 30/284 • Number of events 31 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.	9.2% 26/284 • Number of events 28 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.	2.9% 13/444 • Number of events 13 • From first dose of study drug through 76 weeks. Only SAEs caused by a protocol-mandated intervention were reported from time of Informed Consent through first study intervention. After initiation of study intervention (Day 1) through final safety follow-up visit, all AE and SAE information were collected.

Additional Information

Pablo Velazquez-Martin, MD

Kodiak Sciences Inc.

Phone: 1 (650) 281-0850

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER