A Study to Evaluate the Efficacy, Durability, and Safety... | NCT04592419

NCT04592419

ID	Type	Description	Link
2020-001061-37	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
KSI-301 (Arm A)	Experimental	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.	Drug: KSI-301 Other: Sham Procedure
Aflibercept (Arm B)	Active Comparator	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.	Drug: Aflibercept Other: Sham Procedure

Name	Type	Description	Arm Group Labels	Other Names
KSI-301	Drug	Intravitreal Injection	KSI-301 (Arm A)
Aflibercept

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 to Week 24
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 to Week 24

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 - Week 48
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent prior to participation in the study.
Treatment-naïve macular edema of 6 months duration or less due to CRVO or BRVO. Participants with hemiretinal vein occlusion will be included as CRVO.
BCVA ETDRS letter score between 80 and 25 (20/25 to 20/320 Snellen equivalent), inclusive in the Study Eye.
CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center
Decrease in vision determined by the Investigator to be primarily the result of ME secondary to RVO.
Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

Macular edema in the Study Eye for reasons other than RVO
Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.
Uncontrolled glaucoma in the Study Eye.
Active retinal disease other than the condition under investigation in the Study Eye.
Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention alter visual acuity during the study
Active or suspected ocular or periocular infection or inflammation
Any prior use of an approved or investigational treatment for macular edema secondary to RVO in the Study Eye (e.g. anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).
Women who are pregnant or lactating or intending to become pregnant during the study.
Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest
Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event.
History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
Other protocol-specified exclusion criteria may apply.

Name	Affiliation	Role
Pablo Velazquez-Martin, MD	Kodiak Sciences Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Northwest Arkansas Retina Associates		Phoenix	Arizona	85014	United States
Retinal Research Institute, LLC

PubMed Identifier	Type	Citation	Retractions
42054088	Derived	Temkar S, Rajasekar G, Shah AD, Shaikh N, Deb AK, Basa K. Retinal vein occlusion-related macular edema: An updated review of current evidence and future directions. Indian J Ophthalmol. 2026 May 1;74(5):715-723. doi: 10.4103/IJO.IJO_3361_25. Epub 2026 Apr 29.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 2, 2021	Apr 4, 2024

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	Aflibercept (Arm B)	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
18-64 years	BG000126 BG001142 BG002268
65-74 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000141 BG001138 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00031 BG00129 BG002

Geographic Region

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
North America	BG000193 BG001193 BG002

Blood Pressure at Baseline

Mean

Standard Deviation

mmHG

Title

Denominators

Categories

Systolic

Title	Measurements
	BG000139.1± 16.66 BG001138.7± 16.42 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.

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

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.

Posted

Least Squares Mean

Standard Error

ETDRS Letters

Day 1 to Week 24

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000220 OG001218

Title

Denominators

Categories

Title	Measurements
	OG00014.2± .81 OG00115.6± .79

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	MMRM model with treatment, visit, treatment × visit interaction, baseline BCVA, disease duration, and geographical location as covariates.	.0004		Adjusted mean difference	-1.4	Standard Error of the Mean	.87	2-Sided	95.02	-3.11	0.30					Non-Inferiority	The maximum clinically acceptable true difference between KSI-301 and aflibercept among BRVO participants to be considered non-inferior is 4.5 ETDRS letters, i.e. the non-inferiority margin (NI) is 4.5 letters.

Primary

Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.

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

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.

Posted

Least Squares Mean

Standard Error

ETDRS Letters

Day 1 to Week 24

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.

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

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.

Posted

Mean

Standard Deviation

ETDRS Letters

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	Aflibercept (Arm B)

Secondary

Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.

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.

Posted

Count of Participants

Participants

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	Aflibercept (Arm B)

Secondary

Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants

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.

Posted

Count of Participants

Participants

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	Aflibercept (Arm B)

Secondary

Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants.

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.

Posted

Count of Participants

Participants

Day 1 - Week 48.

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants.

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.

Posted

Count of Participants

Participants

Baseline - Week 48

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants.

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.

Posted

Count of Participants

Participants

Baseline - Week 48

ID	Title	Description
OG000	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.

Secondary

Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants.

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

Posted

Mean

Standard Deviation

micrometers (um)

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	Aflibercept (Arm B)

Secondary

Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants.

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

Posted

Mean

Standard Deviation

micrometers (um)

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	Aflibercept (Arm B)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. 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.	3	284	36	284	73	284
EG001	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. 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.	1	284	23	284	66	284
EG002	KSI-301 5mg Extension Phase	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.	2	444	18	444	53	444

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0003 events2 affected284 at risk EG0012 events2 affected284 at risk EG0020 events0 affected444 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Atrioventricular block	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Cardiac failure	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0012 events2 affected284 at risk EG0020 events0 affected444 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Myocardial infarction	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Urinary tract infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected284 at risk EG0011 events1 affected284 at risk EG0021 events1 affected444 at risk
COVID-19	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Furuncle	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Pneumonia	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Sepsis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0022 events2 affected444 at risk
Vestibular neuronitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Epididymitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Orchitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Retinal detachment - Fellow eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Glaucoma - Study eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Lens dislocation - Study eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Rhegmatogenous retinal detachment - Study eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Vitritis - Study eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Retinal vein occlusion - Study eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0012 events2 affected284 at risk EG0020 events0 affected444 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Waldenstrom's macroglobulinaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0012 events1 affected284 at risk EG0020 events0 affected444 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Cerebral infarction	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Myelopathy	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events1 affected284 at risk EG0012 events2 affected284 at risk EG0020 events0 affected444 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Arteriosclerosis	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Giant cell arteritis	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Intraocular pressure increased - Study eye	Investigations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Device malfunction	Product Issues	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Volvulus	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Non-cardiac chest pain	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0012 events2 affected284 at risk EG0020 events0 affected444 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected284 at risk EG0020 events0 affected444 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0022 events2 affected444 at risk
Dementia	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Lacunar infarction	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Nerve compression	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Syncope	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Bronchial neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Sarcomatoid carcinoma of the lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Angina unstable	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Colitis	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Essential hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Shock	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Cholestasis	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Fall	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Coronary artery disease	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0010 events0 affected284 at risk EG0021 events1 affected444 at risk
Retinal detachment - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected284 at risk EG0020 events0 affected444 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Conjunctival haemorrhage - Study eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00027 events24 affected284 at risk EG00124 events22 affected284 at risk EG0028 events8 affected444 at risk
COVID-19	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG00030 events30 affected284 at risk EG00123 events23 affected284 at risk EG00233 events32 affected444 at risk
Hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG00031 events30 affected284 at risk EG00128 events26 affected284 at risk EG00213 events13 affected444 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.

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.

Aflibercept: Intravitreal Injection

ID	Term
D008269	Macular Edema
D012170	Retinal Vein Occlusion
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases
D014786	Vision Disorders
D015354	Vision, Low

ID	Term
D008268	Macular Degeneration
D020246	Venous Thrombosis
D013927	Thrombosis
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D015785	Eye Diseases, Hereditary
D012678	Sensation Disorders
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms