A Study to Evaluate the Efficacy and Safety of Intravitre... | NCT05066230

Label	Type	Description	Intervention Names
KSI-301 - Treatment Group A	Experimental	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92	Drug: KSI-301
Treatment Group B	Sham Comparator	Sham injection on the same schedule as Treatment Group A	Other: Sham injection

Name	Type	Description	Arm Group Labels	Other Names
KSI-301	Drug	Intravitreal injection	KSI-301 - Treatment Group A
Sham injection

Measure	Description	Time Frame
Percentage of Patients Improving ≥2 Steps on DRSS	Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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).	Day 1 to Week 48

Measure	Description	Time Frame
Percentage of Patients Developing Any Sight-Threatening Complication	Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48	Day 1 to Week 48

Measure	Description	Time Frame
Time to First Development of DME	Time to first development of Diabetic Macular Edema (DME) through Week 48	Day 1 to Week 48
Mean Change in OCT CST	Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline by visit over time

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent prior to participation in the study.
Type 1 or 2 diabetes mellitus
Moderately severe to severe NPDR in the Study Eye (DRSS levels 47 and 53 as determined by the reading center), in which pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator.
BCVA ETDRS letter score in the Study Eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
HbA1c of ≤12%.
Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

Presence of center-involved DME in the Study Eye
Prior PRP in the Study Eye.
Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye.
Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME.
Prior intravitreal or periocular steroid in the Study Eye for DR or DME.
Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye.
Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or alter visual acuity during the study
Active or suspected ocular or periocular infection or inflammation.
Women who are pregnant or lactating or intending to become pregnant during the study.
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.
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.
Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥ 100 mmHg while at rest.
Other protocol-specified exclusion criteria may apply.

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

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

ID	Title	Description
FG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
FG001	Treatment Group B

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 17, 2021	Jul 11, 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

Percentage of Patients Improving ≥2 Steps on DRSS

Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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).

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants	OG000128 OG001125

Title

Denominators

Categories

Title	Measurements
	OG00052 OG0012

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		Cochran-Mantel-Haenszel	Cochran-Mantel-Haentzel test stratified by baseline DRSS level (≤level 47 vs. ≥level 53) and HbA1c level (≤8.5% vs. >8.5%).	<0.0001		Difference of weighted percentages	39.7			2-Sided	95.02	31.3	48.1			Weighted percentages are based on weighted average of observed estimates across strata using CMH weights. The CI are based on the normal approximation to the binomial proportions.		Superiority

Secondary

Percentage of Patients Developing Any Sight-Threatening Complication

Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units

Secondary

Percentage of Patients Improving ≥3 Steps on DRSS

Percentage of patients improving ≥3 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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).

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Secondary

Percentage of Patients Developing PDR

Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Secondary

Percentage of Patients Developing PDR or ASNV

Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) from baseline through Week 48

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Secondary

Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR

Percentage of patients developing vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Secondary

Percentage of Patients Developing DME

Percentage of patients developing Diabetic Macular Edema (DME) from baseline through Week 48

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Secondary

Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS

Percentage of patients with a ≥2-step or ≥3-step worsening on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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).

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Secondary

Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA

Percentage of patients who lost ≥5, ≥10, or ≥15 letters in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. 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 sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. The Overall Number of Participants Analyzed were 128 and 125, but the number analyzed for each row is different depending on the number of participants with data for that row.

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Secondary

Time to First Development of PDR, ASNV, or DME

Time to first development of Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), or Diabetic Macular Edema (DME) through Week 48

Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.

Posted

Median

95% Confidence Interval

Months

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts

Secondary

Time to First Development of PDR or ASNV

Time to first development of Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) through Week 48

Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.

Posted

Median

95% Confidence Interval

Months

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Secondary

Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR

Time to first development of vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) through Week 48

Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.

Posted

Median

95% Confidence Interval

Months

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units

Other Pre-specified

Time to First Development of DME

Time to first development of Diabetic Macular Edema (DME) through Week 48

Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.

Posted

Median

95% Confidence Interval

Months

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Other Pre-specified

Mean Change in OCT CST

Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline by visit over time

Posted

Mean

Standard Deviation

Microns

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Units	Counts
Participants

Other Pre-specified

Mean Change in BCVA

Mean change in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. 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.

Posted

Mean

Standard Deviation

ETDRS Letters

Day 1 to Week 48

ID	Title	Description
OG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
OG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG0030 events0 affected115 at risk
Angina unstable	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Atrioventricular block	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Atrioventricular block second degree	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Pulseless electrical activity	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Deafness	Ear and labyrinth disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Retinal vein occlusion - Fellow Eye	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Chest pain	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0022 events2 affected120 at risk EG003
Impaired healing	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Gallbladder rupture	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Localised infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0012 events2 affected125 at risk EG0022 events2 affected120 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Cellulitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Complicated appendicitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Infected cyst	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Sepsis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Septic shock	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Appendicitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Cellulitis staphylococcal	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Mycoplasma infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0002 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Periprosthetic fracture	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0021 events1 affected120 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Cerebral arteriosclerosis	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0021 events1 affected120 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Hypertensive emergency	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0011 events1 affected125 at risk EG0020 events0 affected120 at risk EG003
Osteomyelitis acute	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0021 events1 affected120 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0021 events1 affected120 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0021 events1 affected120 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0021 events1 affected120 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0021 events1 affected120 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected128 at risk EG0010 events0 affected125 at risk EG0020 events0 affected120 at risk EG003

ID	Term
D003930	Diabetic Retinopathy
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases
D014786	Vision Disorders

ID	Term
D003925	Diabetic Angiopathies
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D048909	Diabetes Complications
D003920	Diabetes Mellitus
D004700	Endocrine System 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

ID	Title	Description
BG000	KSI-301 - Treatment Group A	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection
BG001	Treatment Group B	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.
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 - Treatment Group A (Day 1 to Week 48)	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection	1	128	18	128	49	128
EG001	Treatment Group B (Day 1 to Week 48)	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.	1	125	12	125	51	125
EG002	KSI-301 - Treatment Group A (Post Week 48 to End of Study)	Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection	1	120	8	120	15	120
EG003	Treatment Group B (Post Week 48 to End of Study)	Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.	0	115	3	115	9	115

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cataract - Study Eye	Eye disorders	MedDRA 23.1	Systematic Assessment	EG00014 events13 affected128 at risk EG0015 events5 affected125 at risk EG0023 events3 affected120 at risk EG0030 events0 affected115 at risk
Conjunctival haemorrhage - Study Eye	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0009 events9 affected128 at risk EG0015 events4 affected125 at risk EG0021 events1 affected120 at risk EG003
Cataract - Fellow Eye	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0007 events7 affected128 at risk EG0013 events3 affected125 at risk EG0021 events1 affected120 at risk EG003
Diabetic retinal oedema - Study Eye	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected128 at risk EG00119 events18 affected125 at risk EG0023 events3 affected120 at risk EG003
Diabetic retinopathy - Study Eye	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected128 at risk EG0018 events8 affected125 at risk EG0021 events1 affected120 at risk EG003
COVID-19	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0009 events9 affected128 at risk EG0017 events6 affected125 at risk EG0021 events1 affected120 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00015 events15 affected128 at risk EG0018 events8 affected125 at risk EG0023 events3 affected120 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG00013 events12 affected128 at risk EG00110 events10 affected125 at risk EG0022 events2 affected120 at risk EG003