A Study to Evaluate the Efficacy, Durability, and Safety... | NCT04603937

NCT04603937

ID	Type	Description	Link
2020-001063-82	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions 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) 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

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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.

Contacts/Locations Module

Name	Affiliation	Role
Pablo Velazquez-Martin, 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

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

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

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

FG000229 subjectsThe number of participants who started in KSI-301 (Arm A) reflects those who actually received the treatment.

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.

Arm/Group Information

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

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00062.2± 9.34 BG00161.6± 9.90 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00097 BG00179 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00042 BG00158 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Geographic Region

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
North America	BG000149 BG001147 BG002

BCVA in the Study Eye, Letters

Mean

Standard Deviation

Letters

Title

Denominators

Categories

Title	Measurements
	BG00064.2± 11.43 BG00164.3± 11.21 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 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	OG000229 OG001228

Title

Denominators

Categories

Title	Measurements
	OG0006.7± 0.80 OG00111.5± 0.81

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.	> 0.9999		Adjusted mean difference	-4.7	Standard Error of the Mean	0.97	2-Sided	95.04	-6.65	-2.81					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 NCT04611152 to review demographics, other study details and adverse events for participants in KS301P104 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 KS301P105

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 KS301P105. 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. One patient was randomized to KSI-301, but received aflibercept.

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) 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.

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) 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.	4	228	53	228	113	228
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.	6	229	57	229	104	229

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events1 affected229 at risk
Blood loss anaemia	Blood and lymphatic system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0004 events3 affected228 at risk EG0014 events4 affected229 at risk
Myocardial infarction	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected228 at risk EG0013 events3 affected229 at risk
Cardiac failure acute	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected229 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0015 events4 affected229 at risk
Cardiac arrest	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected229 at risk
Angina unstable	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events1 affected228 at risk EG0010 events0 affected229 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Atrioventricular block	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Coronary artery disease	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0013 events3 affected229 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Angina pectoris	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Cardiomyopathy	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Vertigo	Ear and labyrinth disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Cataract - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected229 at risk
Angle closure glaucoma - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Cataract - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Cataract subcapsular - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Eye haemorrhage - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Retinal artery occlusion - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Retinal detachment - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Retinal vein occlusion - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Rhegmatogenous retinal detachment - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Macular fibrosis - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Macular fibrosis - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Rhegmatogenous retinal detachment - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Vitreous haemorrhage - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events1 affected229 at risk
Death	General disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Asthenia	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Chest pain	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Oedema peripheral	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Pyrexia	General disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Pneumonia	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0005 events5 affected228 at risk EG0012 events2 affected229 at risk
COVID-19	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected228 at risk EG0014 events4 affected229 at risk
Osteomyelitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected228 at risk EG0013 events3 affected229 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected228 at risk EG0014 events4 affected229 at risk
Localised infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0012 events2 affected229 at risk
Sepsis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0012 events2 affected229 at risk
Cellulitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected229 at risk
Bronchitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Diabetic foot infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Endocarditis bacterial	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Endophthalmitis - Fellow Eye	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Enterococcal infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Erysipelas	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Infected skin ulcer	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Osteomyelitis chronic	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Septic shock	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Staphylococcal infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Tooth abscess	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Urosepsis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Abscess limb	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Diverticulitis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0013 events1 affected229 at risk
Endophthalmitis - Study Eye	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Helicobacter gastritis	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
West Nile viral infection	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Procedural pneumothorax	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Neuropathic arthropathy	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Connective tissue inflammation	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Immune-mediated myositis	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected229 at risk
Acral lentiginous melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected229 at risk
Basal ganglia haemorrhage	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Encephalomalacia	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Lumbosacral radiculopathy	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Ischaemic stroke	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0014 events4 affected229 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected229 at risk
Carotid artery aneurysm	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Lacunar infarction	Nervous system disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Mental status changes	Psychiatric disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Hallucination	Psychiatric disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0004 events4 affected228 at risk EG0012 events2 affected229 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected228 at risk EG0011 events1 affected229 at risk
Renal failure	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0002 events2 affected228 at risk EG0012 events1 affected229 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Urinary retention	Renal and urinary disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0003 events3 affected228 at risk EG0012 events2 affected229 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected229 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0012 events1 affected229 at risk
Henoch-Schonlein purpura	Skin and subcutaneous tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected229 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Hypertensive crisis	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected229 at risk
Hypertensive emergency	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Hypertensive urgency	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected229 at risk
Hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Orthostatic hypotension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Peripheral ischaemia	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk
Shock haemorrhagic	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected229 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cataract - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00034 events33 affected228 at risk EG00115 events15 affected229 at risk
Conjunctival haemorrhage - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00025 events22 affected228 at risk EG00110 events8 affected229 at risk
Diabetic retinal oedema - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00016 events14 affected228 at risk EG00125 events24 affected229 at risk
Cataract - Fellow Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00012 events12 affected228 at risk EG00112 events12 affected229 at risk
Diabetic retinal oedema - Study Eye	Eye disorders	MedDRA version 23.1	Systematic Assessment	EG00015 events12 affected228 at risk EG0015 events4 affected229 at risk
COVID-19	Infections and infestations	MedDRA version 23.1	Systematic Assessment	EG00033 events32 affected228 at risk EG00134 events34 affected229 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 23.1	Systematic Assessment	EG00023 events22 affected228 at risk EG00123 events22 affected229 at risk
Hypertension	Vascular disorders	MedDRA version 23.1	Systematic Assessment	EG00024 events23 affected228 at risk EG00124 events23 affected229 at risk

First MCP Posted Date

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

Ancestor Terms

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	Term
C533178	aflibercept