Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration. (NCT NCT04049266)

Last Updated: 2024-07-18

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

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

559 participants

Primary outcome timeframe

Year 1

Results posted on

2024-07-18

Participant Flow

Participants were recruited based on physician referral at 72 medical centers between September 2019 and November 2020. The first participant was enrolled on 08 October 2019 and the last on 24 November 2020.

Of 785 participants screened, 559 were randomized to treatment. Two randomized subjects (one subject in KSI-301 arm and one subject in aflibercept arm) never received treatment, so do not have reason for not completing treatment.

Participant milestones

Participant milestones
Measure	KSI-301 5 mg Q12W-Q20W Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52.
Overall Study STARTED	277	280
Overall Study COMPLETED	240	254
Overall Study NOT COMPLETED	37	26

Reasons for withdrawal

Reasons for withdrawal
Measure	KSI-301 5 mg Q12W-Q20W Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52.
Overall Study Adverse Event	16	9
Overall Study Non-compliance with study drug	0	3
Overall Study Withdrawal by Subject	6	10
Overall Study Lost to Follow-up	2	2
Overall Study Progressive disease	11	2
Overall Study Physician Decision	1	0
Overall Study Patient moved out of state	1	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KSI-301 5 mg Q12W-Q20W n=277 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=280 Participants Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52.	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	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	259 Participants n=5 Participants	257 Participants n=7 Participants	516 Participants n=5 Participants
Age, Continuous	76.6 years STANDARD_DEVIATION 7.35 • n=5 Participants	76.2 years STANDARD_DEVIATION 8.27 • n=7 Participants	76.4 years STANDARD_DEVIATION 7.82 • n=5 Participants
Sex: Female, Male Female	178 Participants n=5 Participants	168 Participants n=7 Participants	346 Participants n=5 Participants
Sex: Female, Male Male	99 Participants n=5 Participants	112 Participants n=7 Participants	211 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	9 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	260 Participants n=5 Participants	271 Participants n=7 Participants	531 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	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	271 Participants n=5 Participants	272 Participants n=7 Participants	543 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment North America	229 participants n=5 Participants	235 participants n=7 Participants	464 participants n=5 Participants
Region of Enrollment Europe	48 participants n=5 Participants	45 participants n=7 Participants	93 participants n=5 Participants
BCVA in the Study Eye, Letters	63.6 Letters STANDARD_DEVIATION 12.23 • n=5 Participants	63.6 Letters STANDARD_DEVIATION 12.34 • n=7 Participants	63.6 Letters STANDARD_DEVIATION 12.27 • n=5 Participants

PRIMARY outcome

Timeframe: Year 1

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection in Year 1. Subjects will be analyzed according to their randomized treatment.

Outcome measures

Outcome measures
Measure	KSI-301 5 mg Q12W-Q20W n=277 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=280 Participants Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48 and 52, Full Analysis Set Year 1	1 ETDRS Letters Standard Error 0.78	7 ETDRS Letters Standard Error 0.77

SECONDARY outcome

Timeframe: Year 1

Population: Subjects with Available Data at the Planned Durability Assessment at Year 1

Percentage of subjects on KSI-301 arm achieving a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment Interval based on individualized treatment response

Outcome measures

Outcome measures
Measure	KSI-301 5 mg Q12W-Q20W n=234 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Percentage of Subjects on KSI-301 Arm With a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment Interval Number of participants on the KSI-301 Q12W	71 Participants	—
Percentage of Subjects on KSI-301 Arm With a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment Interval Number of participants on the KSI-301 Q16W	24 Participants	—
Percentage of Subjects on KSI-301 Arm With a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment Interval Number of participants on the KSI-301 Q20W	139 Participants	—

SECONDARY outcome

Timeframe: Year 1

Population: All randomized subjects who received at least one treatment injection in Year 1 with available data at Year 1 for analysis. Number of participants in each Row Title is not mutually exclusive as number of participants who gained \>=15 ETDRS letters includes participants who gained \>=10 ETDRS letters and participants who gained \>=5 ETDRS letters.

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 5 mg Q12W-Q20W n=238 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=254 Participants Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Percentage of Subjects Gaining ≥ 5, ≥10 and ≥15 Letters in BCVA From Baseline in the Study Eye, Full Analysis Set Year 1 Gain >=5 ETDRS Letters at Year 1	103 Participants	148 Participants
Percentage of Subjects Gaining ≥ 5, ≥10 and ≥15 Letters in BCVA From Baseline in the Study Eye, Full Analysis Set Year 1 Gain >=10 ETDRS Letters at Year 1	66 Participants	87 Participants
Percentage of Subjects Gaining ≥ 5, ≥10 and ≥15 Letters in BCVA From Baseline in the Study Eye, Full Analysis Set Year 1 Gain >=15 ETDRS Letters at Year 1	31 Participants	46 Participants

SECONDARY outcome

Timeframe: Year 1

Population: All randomized subjects who received at least one treatment injection in Year 1 with available data at Year 1 for analysis.

Outcome measures

Outcome measures
Measure	KSI-301 5 mg Q12W-Q20W n=238 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=254 Participants Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Percentage of Subjects Who Achieving BCVA Snellen Equivalent of 20/40 or Better in the Study Eye at Year 1	119 Participants	165 Participants

SECONDARY outcome

Timeframe: Year 1

Population: All randomized subjects who received at least one treatment injection in Year 1 with available data at Year 1 for analysis.

Outcome measures

Outcome measures
Measure	KSI-301 5 mg Q12W-Q20W n=238 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=254 Participants Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Percentage of Subjects With BCVA Snellen Equivalent of 20/200 or Worse in the Study Eye at Year 1	13 Participants	8 Participants

SECONDARY outcome

Timeframe: Year 1

Population: Full analysis set defined as all randomized subjects who received at least one treatment injection in Year 1. 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 5 mg Q12W-Q20W n=277 Participants Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=280 Participants Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Day 1	-96.1 Microns Standard Deviation 123.39	-134.1 Microns Standard Deviation 111.17

Adverse Events

KSI-301 5 mg Q12W-Q20W

Serious events: 35 serious events

Other events: 82 other events

Deaths: 4 deaths

Aflibercept 2 mg Q8W

Serious events: 33 serious events

Other events: 84 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	KSI-301 5 mg Q12W-Q20W n=277 participants at risk Participants randomized to this arm received 5 milligrams (mg) KSI-301 intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 8, followed by 5 mg KSI-301 IVT injections based on disease activity assessments and may vary from Q12W to Q20W until Week 52.	Aflibercept 2 mg Q8W n=280 participants at risk Participants randomized to this arm received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 8, followed by 2 mg aflibercept IVT injections Q8W to Week 52
Eye disorders Neovascular age-related macular degeneration - Fellow eye	6.9% 19/277 • Number of events 19 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.	9.3% 26/280 • Number of events 26 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.
Eye disorders Retinal haemorrhage - Study eye	6.1% 17/277 • Number of events 18 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.	1.4% 4/280 • Number of events 5 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.
Eye disorders Cataract - Study eye	5.4% 15/277 • Number of events 15 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.	3.6% 10/280 • Number of events 10 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.
Eye disorders Conjunctival haemorrhage - Study eye	4.7% 13/277 • Number of events 14 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.	8.6% 24/280 • Number of events 30 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.
Infections and infestations Urinary tract infection	5.4% 15/277 • Number of events 18 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.	5.7% 16/280 • Number of events 18 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.
Vascular disorders Hypertension	5.4% 15/277 • Number of events 15 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.	5.7% 16/280 • Number of events 16 • Adverse Events (AEs) reported through Week 52 or Early Termination (ET) if occurred before Week 52. Safety results for the KSI-301 5mg arm are presented together as patients treated with Q12W dosing received 6 total doses in Year 1 and the patients treated with Q20W dosing received 5 total doses in Year 1. Therefore, presenting all treatment intervals together provides a more robust dataset to evaluate the safety profile of KSI-301.

Additional Information

Pablo Velazquez-Martin, MD

Kodiak Sciences Inc.

Phone: 1 (650) 281-0850

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER