Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) (NCT NCT04964089)

Last Updated: 2024-07-03

Results Overview

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

COMPLETED

Study phase

PHASE3

Target enrollment

557 participants

Primary outcome timeframe

Day 1 to Week 48

Results posted on

2024-07-03

Participant Flow

Participants were recruited based on physician referral at 94 medical centers between June 2021 and April 2022. The first participant was enrolled on 23 June 2021 and the last on 07 April 2022.

Of 815 participants screened, 557 were randomized to treatment.

Participant milestones

Participant milestones
Measure	KSI-301 (Treatment Group A) Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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	276	281
Overall Study COMPLETED	253	268
Overall Study NOT COMPLETED	23	13

Reasons for withdrawal

Reasons for withdrawal
Measure	KSI-301 (Treatment Group A) Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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	8	6
Overall Study Non-compliance with study schedule	1	0
Overall Study Withdrawal by Subject	6	5
Overall Study Lost to Follow-up	1	1
Overall Study Progressive disease	4	0
Overall Study Physician Decision	1	0
Overall Study Participant did not want to continue study treatment	1	0
Overall Study Participant moved to different state	1	0
Overall Study Participant decided to discontinue	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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=557 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	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Age, Categorical >=65 years	257 Participants n=5 Participants	263 Participants n=7 Participants	520 Participants n=5 Participants
Age, Continuous	76.9 years STANDARD_DEVIATION 8.21 • n=5 Participants	77.2 years STANDARD_DEVIATION 7.84 • n=7 Participants	77.0 years STANDARD_DEVIATION 8.02 • n=5 Participants
Sex: Female, Male Female	159 Participants n=5 Participants	180 Participants n=7 Participants	339 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants	101 Participants n=7 Participants	218 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	260 Participants n=5 Participants	267 Participants n=7 Participants	527 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	269 Participants n=5 Participants	276 Participants n=7 Participants	545 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Geographic Region North America	225 Participants n=5 Participants	228 Participants n=7 Participants	453 Participants n=5 Participants
Geographic Region Rest of World	51 Participants n=5 Participants	53 Participants n=7 Participants	104 Participants n=5 Participants
BCVA in the Study Eye	63.7 Letters STANDARD_DEVIATION 13.06 • n=5 Participants	64.0 Letters STANDARD_DEVIATION 13.09 • n=7 Participants	63.8 Letters STANDARD_DEVIATION 13.07 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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 Best Corrected Visual Acuity (BCVA) From Day 1 to the Average of Non-missing BCVA Values of Weeks 40, 44 and 48.	2.5 ETDRS Letters Standard Error 0.78	4.6 ETDRS Letters Standard Error 0.76

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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 Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 2	2.8 ETDRS Letters Standard Deviation 6.48	2.9 ETDRS Letters Standard Deviation 7.12
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 4	3.4 ETDRS Letters Standard Deviation 7.05	4.2 ETDRS Letters Standard Deviation 7.29
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 8	3.7 ETDRS Letters Standard Deviation 8.52	5.1 ETDRS Letters Standard Deviation 7.86
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 12	3.8 ETDRS Letters Standard Deviation 8.83	5.4 ETDRS Letters Standard Deviation 7.90
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 16	3.6 ETDRS Letters Standard Deviation 9.09	4.9 ETDRS Letters Standard Deviation 8.54
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 20	3.9 ETDRS Letters Standard Deviation 9.60	5.7 ETDRS Letters Standard Deviation 8.97
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 24	4.5 ETDRS Letters Standard Deviation 9.29	6.0 ETDRS Letters Standard Deviation 9.45
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 28	4.5 ETDRS Letters Standard Deviation 9.75	6.1 ETDRS Letters Standard Deviation 9.49
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 32	3.9 ETDRS Letters Standard Deviation 10.32	6.1 ETDRS Letters Standard Deviation 9.86
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 36	3.7 ETDRS Letters Standard Deviation 10.58	6.1 ETDRS Letters Standard Deviation 9.77
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 40	4.0 ETDRS Letters Standard Deviation 11.05	5.6 ETDRS Letters Standard Deviation 10.75
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 44	4.7 ETDRS Letters Standard Deviation 9.99	5.9 ETDRS Letters Standard Deviation 10.71
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Week 48	3.7 ETDRS Letters Standard Deviation 11.12	5.4 ETDRS Letters Standard Deviation 11.36

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Categorical improvements in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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.
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 2	100 Participants	96 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 4	110 Participants	129 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 8	119 Participants	151 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 12	124 Participants	148 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 16	119 Participants	143 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 20	121 Participants	161 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 24	130 Participants	156 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 28	122 Participants	154 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 32	132 Participants	168 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 36	120 Participants	158 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 40	116 Participants	156 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 44	126 Participants	151 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥5 ETDRS Letters at Week 48	111 Participants	150 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 2	31 Participants	37 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 4	44 Participants	54 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 8	52 Participants	72 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 12	55 Participants	72 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 16	62 Participants	68 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 20	66 Participants	86 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 24	70 Participants	90 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 28	66 Participants	87 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 32	57 Participants	95 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 36	66 Participants	81 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 40	67 Participants	80 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 44	67 Participants	86 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥10 ETDRS Letters at Week 48	65 Participants	85 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 2	12 Participants	11 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 4	18 Participants	21 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 8	24 Participants	28 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 12	20 Participants	29 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 16	24 Participants	33 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 20	28 Participants	33 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 24	33 Participants	42 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 28	36 Participants	46 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 32	32 Participants	37 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 36	32 Participants	44 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 40	33 Participants	45 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 44	34 Participants	48 Participants
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Gain ≥15 ETDRS Letters at Week 48	35 Participants	49 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Categorical worsening in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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.
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 2	20 Participants	28 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 4	27 Participants	19 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 8	41 Participants	22 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 12	35 Participants	24 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 16	35 Participants	31 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 20	35 Participants	27 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 24	34 Participants	31 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 28	38 Participants	31 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 32	41 Participants	35 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 36	47 Participants	32 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 40	33 Participants	41 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 44	33 Participants	33 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 5 ETDRS Letters at Week 48	39 Participants	38 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 2	6 Participants	10 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 4	6 Participants	4 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 8	10 Participants	8 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 12	15 Participants	9 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 16	15 Participants	15 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 20	16 Participants	14 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 24	17 Participants	12 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 28	21 Participants	14 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 32	23 Participants	16 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 36	22 Participants	18 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 40	21 Participants	24 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 44	18 Participants	21 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 10 ETDRS Letters at Week 48	24 Participants	25 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 2	3 Participants	4 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 4	4 Participants	4 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 8	4 Participants	4 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 12	6 Participants	3 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 16	9 Participants	5 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 20	7 Participants	6 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 24	7 Participants	6 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 28	7 Participants	5 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 32	10 Participants	9 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 36	14 Participants	9 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 40	18 Participants	13 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 44	8 Participants	11 Participants
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Loss ≥ 15 ETDRS Letters at Week 48	15 Participants	13 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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.
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 36	147 Participants	179 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Baseline	122 Participants	129 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 2	148 Participants	152 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 4	156 Participants	165 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 8	156 Participants	165 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 12	148 Participants	171 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 16	149 Participants	172 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 20	151 Participants	179 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 24	158 Participants	183 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 28	151 Participants	175 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 32	147 Participants	174 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 40	151 Participants	174 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 44	149 Participants	178 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Snellen Equivalent of 20/40 or Better at Week 48	144 Participants	175 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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.
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Baseline	17 Participants	15 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 2	11 Participants	12 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 4	10 Participants	14 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 8	11 Participants	13 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 12	11 Participants	12 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 16	11 Participants	10 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 20	13 Participants	13 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 24	11 Participants	13 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 28	12 Participants	13 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 32	14 Participants	18 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 36	14 Participants	13 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 40	14 Participants	17 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 44	9 Participants	15 Participants
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Snellen Equivalent of 20/200 or Worse at Week 48	15 Participants	15 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment.

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) as assessed by a central reading center.

Outcome measures

Outcome measures
Measure	KSI-301 (Treatment Group A) n=276 Participants Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 Participants Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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 Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 2	-72.1 Microns Standard Deviation 83.74	-99.9 Microns Standard Deviation 93.75
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 4	-74.9 Microns Standard Deviation 98.33	-109.4 Microns Standard Deviation 100.87
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 8	-89.1 Microns Standard Deviation 121.13	-122.2 Microns Standard Deviation 109.58
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 12	-97.1 Microns Standard Deviation 118.62	-126.3 Microns Standard Deviation 111.55
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 16	-107.2 Microns Standard Deviation 110.02	-99.2 Microns Standard Deviation 110.47
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 20	-111 Microns Standard Deviation 112.97	-125.5 Microns Standard Deviation 117.39
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 24	-109.9 Microns Standard Deviation 112.82	-101.8 Microns Standard Deviation 113.21
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 28	-114.6 Microns Standard Deviation 111.47	-124.1 Microns Standard Deviation 111.51
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 32	-111.9 Microns Standard Deviation 122.05	-104.3 Microns Standard Deviation 116.09
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 36	-113.6 Microns Standard Deviation 129.84	-124.4 Microns Standard Deviation 112.12
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 40	-113.6 Microns Standard Deviation 115.34	-103.1 Microns Standard Deviation 109.25
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 44	-115.8 Microns Standard Deviation 115.81	-129.4 Microns Standard Deviation 114.70
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 48	-117 Microns Standard Deviation 114	-109.2 Microns Standard Deviation 120.75
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Week 40-48 Average	-114.6 Microns Standard Deviation 113.92	-113.4 Microns Standard Deviation 112.07

Adverse Events

KSI-301 (Treatment Group A)

Serious events: 39 serious events

Other events: 110 other events

Deaths: 4 deaths

Aflibercept (Treatment Group B)

Serious events: 39 serious events

Other events: 80 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	KSI-301 (Treatment Group A) n=276 participants at risk Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection	Aflibercept (Treatment Group B) n=281 participants at risk Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. 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 Neovascular age-related macular degeneration - Fellow eye	8.0% 22/276 • Number of events 23 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	5.3% 15/281 • Number of events 16 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
Eye disorders Vitreous floaters - Study eye	7.6% 21/276 • Number of events 23 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	2.5% 7/281 • Number of events 7 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
Eye disorders Conjunctival haemorrhage - Study eye	7.2% 20/276 • Number of events 26 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	3.9% 11/281 • Number of events 17 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
Infections and infestations COVID-19	12.3% 34/276 • Number of events 35 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	12.5% 35/281 • Number of events 35 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
Infections and infestations Urinary tract infection	5.4% 15/276 • Number of events 23 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	5.7% 16/281 • Number of events 21 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
Vascular disorders Hypertension	6.2% 17/276 • Number of events 17 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	5.0% 14/281 • Number of events 14 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
Investigations Intraocular pressure increased - Study eye	5.4% 15/276 • Number of events 17 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)	0.71% 2/281 • Number of events 2 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET)

Additional Information

Pablo Velazquez-Martin

Kodiak Sciences Inc

Phone: 1 (650) 281-0850

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER