A Trial to Evaluate the Efficacy, Durability, and Safety... | NCT04611152

ID	Type	Description	Link
2020-001062-11	EudraCT Number

Label	Type	Description	Intervention Names
KSI-301 (Arm A)	Experimental	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.	Drug: KSI-301 Other: Sham Procedure
Aflibercept (Arm B)	Active Comparator	Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.	Drug: Aflibercept Other: Sham Procedure

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

Measure	Description	Time Frame
Mean Change in BCVA	Mean change in best-corrected visual acuity (BCVA) from baseline to the average of Weeks 60 and 64 (using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters). Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.	Day 1 to Week 64

Measure	Description	Time Frame
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined	Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Studies KS301P104 and KS301P105 combined. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent prior to participation in the study.
Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening.
BCVA ETDRS letter score between 78 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 DME.
Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%.
Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

Macular edema in the Study Eye considered to be secondary to a cause other than DME.
Active iris or angle neovascularization or neovascular glaucoma in the Study Eye.
High-risk proliferative diabetic retinopathy characteristics in the Study Eye.
History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening.
Tractional retinal detachment 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 or affect macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal membrane).
Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
Any prior use of an approved or investigational treatment for DME 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
UCSD Jacobs Retina Center		La Jolla	California	92037	United States
Retina Consultants of Southern California

ID	Title	Description
FG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 15, 2022	Jul 25, 2024

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 BCVA

Mean change in best-corrected visual acuity (BCVA) from baseline to the average of Weeks 60 and 64 (using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters). Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.

Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or aflibercept). Subjects will be analyzed according to their randomized treatment.

Posted

Least Squares Mean

Standard Error

ETDRS Letters

Day 1 to Week 64

ID	Title	Description
OG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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 for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100. 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	OG000230 OG001230

Title

Denominators

Categories

Title	Measurements
	OG0005.6± 0.83 OG0019.5± 0.85

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 by visit interaction, randomization stratification factors, and continuous baseline BCVA and OCT CST.	0.4162		Adjusted mean difference	-3.8	Standard Error of the Mean	0.84	2-Sided	95.04	-5.47	-2.17					Non-Inferiority	The maximum clinically acceptable true difference between KSI-301 and aflibercept participants to be considered non-inferior is 4.5 ETDRS letters, i.e. the non-inferiority margin

Secondary

Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined

Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Studies KS301P104 and KS301P105 combined. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).

All randomized subjects in Studies KS301P104 and KS301P105 who received any study treatment (KSI-301 or aflibercept) with evaluable results at baseline and evaluable results on or prior to Week 52. The population for studies KS301P104 and KS301P105 are identical in terms of treatment indication and inclusion/exclusion criteria. Please refer to NCT04603937 to review demographics, other study details and adverse events for participants in KS301P105 study.

Posted

Count of Participants

Participants

Day 1 to Week 52

ID	Title	Description
OG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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 Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104

Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Study KS301P104. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).

All randomized subjects who received any study treatment (KSI-301 or aflibercept) with evaluable results at baseline and evaluable results on or prior to Week 52.

Posted

Count of Participants

Participants

Day 1 to Week 52

ID	Title	Description
OG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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 for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100. 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

Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval

Percentage of patients in the KSI-301 arm on a Q8W, Q12W, Q16W, Q20W, or Q24W treatment interval at the primary endpoint. Analyses include KSI-301 patients who completed a treatment interval from Week 56 onwards.

Analyses include KSI-301 patients who completed a treatment interval from Week 56 onwards.

Posted

Count of Participants

Participants

Week 56

ID	Title	Description
OG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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.

Units	Counts
Participants	OG000

Secondary

Mean Number of Intravitreal Injections

Mean number of intravitreal injections from Day 1 to Week 60

Safety Analysis Set includes all patients who received any study treatment (KSI-301 or aflibercept).

Patients will be analyzed according to the study treatment they actually received.

Posted

Mean

Standard Deviation

injections

Day 1 to Week 60

ID	Title	Description
OG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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 for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100. 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 in OCT CST

Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline to the average of Weeks 60 and 64

Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or aflibercept). Subjects will be analyzed according to their randomized treatment.

Posted

Mean

Standard Deviation

Microns

Day 1 to Week 64

ID	Title	Description
OG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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 for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100. 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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy mediastinal	Blood and lymphatic system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Blood loss anaemia	Blood and lymphatic system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Myocardial infarction	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0005 events5 affected230 at risk EG0013 events3 affected230 at risk
Coronary artery disease	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0004 events4 affected230 at risk EG0015 events5 affected230 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0005 events3 affected230 at risk EG0012 events2 affected230 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected230 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0012 events2 affected230 at risk
Angina pectoris	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0012 events1 affected230 at risk
Cardiac failure	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Arrhythmia	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Cardiac failure acute	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Cardiorenal syndrome	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Atrioventricular block	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Retinal detachment - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0013 events3 affected230 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0012 events2 affected230 at risk
Alcoholic pancreatitis	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Diabetic gastroparesis	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Enteritis	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events2 affected230 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events2 affected230 at risk
Gastritis	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Intra-abdominal fluid collection	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Strangulated umbilical hernia	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Catheter site haemorrhage	General disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Generalised oedema	General disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Impaired healing	General disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Complication associated with device	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Death	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Sudden death	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events1 affected230 at risk EG0010 events0 affected230 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
COVID-19	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0005 events5 affected230 at risk EG0012 events2 affected230 at risk
Osteomyelitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0004 events4 affected230 at risk EG0014 events3 affected230 at risk
Cellulitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0005 events4 affected230 at risk EG0011 events1 affected230 at risk
Sepsis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected230 at risk EG0012 events2 affected230 at risk
Gangrene	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected230 at risk EG0011 events1 affected230 at risk
Pneumonia	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected230 at risk EG0011 events1 affected230 at risk
Diabetic gangrene	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected230 at risk
Urinary tract infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected230 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events2 affected230 at risk EG0010 events0 affected230 at risk
Clostridium difficile infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Device related infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Erysipelas	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Metapneumovirus infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Osteomyelitis acute	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Parainfluenzae virus infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Soft tissue infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Diverticulitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Endophthalmitis - Study Eye	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Escherichia infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Implant site infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Necrotising fasciitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Staphylococcal infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected230 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Skull fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events2 affected230 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Burns third degree	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Medical observation	Investigations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected230 at risk EG0014 events3 affected230 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hyperglycaemic hyperosmolar nonketotic syndrome	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events1 affected230 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Psoriatic arthropathy	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events2 affected230 at risk
Endometrial cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hodgkin's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Endocrine neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Neuroendocrine tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Ischaemic stroke	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected230 at risk EG0010 events0 affected230 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected230 at risk
Cerebral infarction	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Encephalopathy	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Aphasia	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Device malfunction	Product Issues	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Behaviour disorder	Psychiatric disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Renal failure	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected230 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0012 events2 affected230 at risk
End stage renal disease	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events2 affected230 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected230 at risk EG0011 events1 affected230 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0004 events2 affected230 at risk EG0010 events0 affected230 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected230 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0012 events2 affected230 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected230 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0005 events4 affected230 at risk EG0016 events6 affected230 at risk
Hypertensive urgency	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected230 at risk
Hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events1 affected230 at risk EG0011 events1 affected230 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected230 at risk
Arteriosclerosis	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hypertensive crisis	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hypotension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected230 at risk
Hypertensive emergency	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected230 at risk EG0013 events3 affected230 at risk

ID	Term
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases
D014786	Vision Disorders
D015354	Vision, Low
D003920	Diabetes Mellitus
D003930	Diabetic Retinopathy
D008269	Macular Edema

ID	Term
D015785	Eye Diseases, Hereditary
D012678	Sensation Disorders
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D003925	Diabetic Angiopathies
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D048909	Diabetes Complications
D008268	Macular Degeneration

ID	Title	Description
BG000	KSI-301 (Arm A)	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100. 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

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) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100. 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.	5	230	61	230	126	230
EG001	Aflibercept (Arm B)	Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100. 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.	5	230	51	230	121	230

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cataract - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00038 events35 affected230 at risk EG00117 events17 affected230 at risk
Diabetic retinal oedema - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00019 events19 affected230 at risk EG00122 events21 affected230 at risk
Conjunctival haemorrhage - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00021 events18 affected230 at risk EG00121 events15 affected230 at risk
Cataract - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00015 events15 affected230 at risk EG00112 events12 affected230 at risk
Dry eye - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00015 events13 affected230 at risk EG00111 events10 affected230 at risk
COVID-19	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG00045 events42 affected230 at risk EG00136 events33 affected230 at risk
Nasopharyngitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0008 events8 affected230 at risk EG00118 events17 affected230 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG00019 events19 affected230 at risk EG00118 events17 affected230 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0008 events8 affected230 at risk EG00114 events14 affected230 at risk
Hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG00033 events30 affected230 at risk EG00134 events31 affected230 at risk