Trial Outcomes & Findings for A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) (NCT NCT04611152)

Last Updated: 2024-08-22

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

460 participants

Primary outcome timeframe

Day 1 to Week 64

Results posted on

2024-08-22

Participant Flow

Participants were recruited based on physician referral at 75 medical centers between September 2020 and February 2022. The first participant was enrolled on 30 September 2020 and the last on 16 February 2022.

Of 670 screened participants, 460 met eligibility criteria and were randomized to treatment. Each participant contributed only one study eye to this study.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	230	230
Overall Study COMPLETED	204	211
Overall Study NOT COMPLETED	26	19

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	9	8
Overall Study Non-compliance with study schedule	1	3
Overall Study Withdrawal by Subject	5	6
Overall Study Lost to Follow-up	11	2

Baseline Characteristics

A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KSI-301 (Arm A) n=230 Participants 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.	Aflibercept (Arm B) n=230 Participants 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.	Total n=460 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	138 Participants n=5 Participants	136 Participants n=7 Participants	274 Participants n=5 Participants
Age, Categorical >=65 years	92 Participants n=5 Participants	94 Participants n=7 Participants	186 Participants n=5 Participants
Age, Continuous	62 years STANDARD_DEVIATION 9.73 • n=5 Participants	61.2 years STANDARD_DEVIATION 10.61 • n=7 Participants	61.6 years STANDARD_DEVIATION 10.18 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	87 Participants n=7 Participants	167 Participants n=5 Participants
Sex: Female, Male Male	150 Participants n=5 Participants	143 Participants n=7 Participants	293 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	37 Participants n=5 Participants	32 Participants n=7 Participants	69 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	193 Participants n=5 Participants	198 Participants n=7 Participants	391 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) White	204 Participants n=5 Participants	200 Participants n=7 Participants	404 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Geographic Region North America	177 Participants n=5 Participants	176 Participants n=7 Participants	353 Participants n=5 Participants
Geographic Region Rest of World	53 Participants n=5 Participants	54 Participants n=7 Participants	107 Participants n=5 Participants
BCVA in the Study Eye, Letters	66.4 Letters STANDARD_DEVIATION 9.78 • n=5 Participants	66.6 Letters STANDARD_DEVIATION 9.60 • n=7 Participants	66.5 Letters STANDARD_DEVIATION 9.68 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Week 64

Population: 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.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=230 Participants 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.	Aflibercept (Arm B) n=230 Participants 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.
Mean Change in BCVA	5.6 ETDRS Letters Standard Error 0.83	9.5 ETDRS Letters Standard Error 0.85

SECONDARY outcome

Timeframe: Day 1 to Week 52

Population: 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.

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).

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=433 Participants 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.	Aflibercept (Arm B) n=437 Participants 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.
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 52

Population: 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.

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).

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=215 Participants 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.	Aflibercept (Arm B) n=219 Participants 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.
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 56

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

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.

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=208 Participants 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.	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.
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval Number of participants on the KSI-301 Q24W	99 Participants	—
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval Number of participants on the KSI-301 Q8W	61 Participants	—
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval Number of participants on the KSI-301 Q12W	21 Participants	—
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval Number of participants on the KSI-301 Q16W	19 Participants	—
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval Number of participants on the KSI-301 Q20W	8 Participants	—

SECONDARY outcome

Timeframe: Day 1 to Week 60

Population: 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.

Mean number of intravitreal injections from Day 1 to Week 60

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=230 Participants 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.	Aflibercept (Arm B) n=230 Participants 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.
Mean Number of Intravitreal Injections	5.9 injections Standard Deviation 1.71	9.2 injections Standard Deviation 1.46

SECONDARY outcome

Timeframe: Day 1 to Week 64

Population: 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.

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

Outcome measures

Outcome measures
Measure	KSI-301 (Arm A) n=230 Participants 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.	Aflibercept (Arm B) n=230 Participants 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.
Mean Change in OCT CST	-140.4 Microns Standard Deviation 132.7	-158.5 Microns Standard Deviation 121.75

Adverse Events

KSI-301 (Arm A)

Serious events: 61 serious events

Other events: 126 other events

Deaths: 5 deaths

Aflibercept (Arm B)

Serious events: 51 serious events

Other events: 121 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	KSI-301 (Arm A) n=230 participants at risk 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.	Aflibercept (Arm B) n=230 participants at risk 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.
Eye disorders Cataract - Study Eye	15.2% 35/230 • Number of events 38 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	7.4% 17/230 • Number of events 17 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Eye disorders Diabetic retinal oedema - Fellow Eye	8.3% 19/230 • Number of events 19 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	9.1% 21/230 • Number of events 22 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Eye disorders Conjunctival haemorrhage - Study Eye	7.8% 18/230 • Number of events 21 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	6.5% 15/230 • Number of events 21 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Eye disorders Cataract - Fellow Eye	6.5% 15/230 • Number of events 15 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	5.2% 12/230 • Number of events 12 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Eye disorders Dry eye - Study Eye	5.7% 13/230 • Number of events 15 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	4.3% 10/230 • Number of events 11 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Infections and infestations COVID-19	18.3% 42/230 • Number of events 45 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	14.3% 33/230 • Number of events 36 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Infections and infestations Nasopharyngitis	3.5% 8/230 • Number of events 8 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	7.4% 17/230 • Number of events 18 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Metabolism and nutrition disorders Diabetes mellitus	8.3% 19/230 • Number of events 19 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	7.4% 17/230 • Number of events 18 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Renal and urinary disorders Chronic kidney disease	3.5% 8/230 • Number of events 8 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	6.1% 14/230 • Number of events 14 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.
Vascular disorders Hypertension	13.0% 30/230 • Number of events 33 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.	13.5% 31/230 • Number of events 34 • Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64.

Additional Information

Pablo Velazquez-Martin

Kodiak Sciences Inc

Phone: 6502810850

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place