DAYLIGHT: 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)

Sponsor

Kodiak Sciences Inc (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04964089

Collaborator

(none)

557

Enrollment

Locations

Arms

21.5

Anticipated Duration (Months)

8.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase 3 study will evaluate the efficacy and safety of KSI-301 compared to aflibercept, in participants with neovascular (wet) age-related macular degeneration (wAMD)

Condition or Disease	Intervention/Treatment	Phase
Wet Age-related Macular Degeneration	Drug: KSI-301 Drug: Aflibercept Other: Sham Procedure	Phase 3

Detailed Description

This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with visual impairment due to treatment-naïve neovascular (wet) age-related macular degeneration (wAMD)

The primary endpoint will be assessed as an average of Weeks 40, 44, and 48; additional secondary endpoints for efficacy will be assessed by visit over time

Study Design

Study Type:

Interventional

Actual Enrollment :

557 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized 1:1 into one of two treatment arms: KSI-301 or aflibercept.Participants will be randomized 1:1 into one of two treatment arms: KSI-301 or aflibercept.

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

For masking purposes, sham injections will be administered at every monthly visit if an active treatment is not administered. To preserve masking, two investigators are required for this study. The masked Investigator will be responsible for the examinations and safety assessments. The unmasked Investigator will perform the injections and post-treatment assessments.

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center, Two-arm, Phase 3 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)

Actual Study Start Date :

Jun 15, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: KSI-301 Intravitreal Injection
Active Comparator: 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.	Drug: Aflibercept Intravitreal Injection Other Names: Eylea Other: 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

Intervention/Treatment

Experimental: 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.

Drug: KSI-301

Intravitreal Injection

Active Comparator: 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.

Drug: Aflibercept

Intravitreal Injection

Other Names:

Eylea

Other: 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.

Outcome Measures

Primary Outcome Measures

Non-inferiority of KSI-301 to aflibercept measured by changes in BCVA. [Day 1 to Week 48]
Demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best-corrected visual acuity (BCVA).

Secondary Outcome Measures

Efficacy of KSI-301 5 mg compared to aflibercept 2 mg based on changes in BCVA [Day 1 to Week 48]
Change from baseline in best corrected visual acuity (BCVA) between the two treatment arms.
Efficacy of KSI-301 5 mg compared to aflibercept 2 mg based on OCT-CST [Day 1 to Week 48]
Change from baseline in central subfield thickness (CST) between the two treatment arms.
Safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg based on the number of ocular and systemic adverse events [Day 1 to Week 52]
Incidence of ocular and systemic adverse events between the two treatment arms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent prior to participation in the study.
Treatment-naïve choroidal neovascularization (CNV) secondary to AMD.
BCVA ETDRS score between 83 and 25 letters, inclusive, in the Study Eye.
Decrease in vision in the Study Eye determined by the Investigator to be primarily the result of wAMD.
Other protocol-specified inclusion criteria may apply

Exclusion Criteria:

BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular).
Active or suspected ocular or periocular infection or inflammation.
CNV secondary to other causes in the Study Eye.
Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or affect macular edema or alter visual acuity during the study.
Uncontrolled glaucoma in the Study Eye.
Significant media opacities, including cataract, in the Study Eye that might interfere with visual acuity, assessment of safety, OCT or fundus photography.
Cataract in the Study Eye that in the judgment of the Investigator is expected to require surgical extraction within 12 months of screening.
Women who are pregnant or lactating or intending to become pregnant during the study.
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.
Uncontrolled blood pressure defined as a systolic value ≥180 mmHg or diastolic value ≥100 mmHg while at rest.
Other protocol-specified exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Research Institute, LLC	Phoenix	Arizona	United States	85014
2	Northwest Arkansas Retina Associates	Springdale	Arkansas	United States	72762
3	California Retina Consultants	Bakersfield	California	United States	93309
4	Eye Medical Center of Fresno	Fresno	California	United States	93720
5	Retina Consultants of Orange County	Fullerton	California	United States	92835
6	UCSD Jacobs Retina Center	La Jolla	California	United States	92037
7	Retina Associates of Orange County	Laguna Hills	California	United States	92653
8	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
9	Retina Consultants of San Diego	Poway	California	United States	92064
10	Retina Consultants of Southern California	Redlands	California	United States	92374
11	Retinal Consultants Medical Group Inc	Sacramento	California	United States	95819
12	Orange County Retina Medical Group	Santa Ana	California	United States	92705
13	Colorado Retina Associates PC	Lakewood	Colorado	United States	80228
14	Retina Group of New England	Waterford	Connecticut	United States	06385
15	Florida Eye Microsurgical Institute	Boynton Beach	Florida	United States	33426
16	Rand Eye Institute	Deerfield Beach	Florida	United States	33064
17	Retina Health Center	Fort Myers	Florida	United States	33907
18	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
19	Florida Eye Associates	Melbourne	Florida	United States	32901
20	Retina Specialty Institute	Pensacola	Florida	United States	32503
21	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33703
22	Retina Associates of Florida	Tampa	Florida	United States	33609
23	Southeast Retina Center	Augusta	Georgia	United States	30909
24	University of Chicago	Chicago	Illinois	United States	60637
25	Springfield Clinic LLP	Springfield	Illinois	United States	62703
26	Talley Eye	Evansville	Indiana	United States	47710
27	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
28	Retina Associates PA	Lenexa	Kansas	United States	66215
29	Retina Associates of Kentucky	Lexington	Kentucky	United States	40509
30	Retina Group of Washington	Chevy Chase	Maryland	United States	20815
31	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland	United States	21740
32	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
33	New England Retina Consultants	Springfield	Massachusetts	United States	01103
34	Vitreo Retinal Associates PC	Worcester	Massachusetts	United States	01603
35	Foundation for Vision Research	Grand Rapids	Michigan	United States	49525
36	Associated Retinal Consultants PC	Royal Oak	Michigan	United States	78073
37	Vitreoretinal Surgery PA	Edina	Minnesota	United States	55435
38	Sierra Eye Associates	Reno	Nevada	United States	89502
39	The Retina Center of New Jersey	Bloomfield	New Jersey	United States	07017
40	NJ Retina	Teaneck	New Jersey	United States	07605
41	Retina-Vitreous Surgeons of Central NY	Liverpool	New York	United States	13088
42	Retina Associates of Western NY	Rochester	New York	United States	14620
43	Western Carolina Retinal Associate PA	Asheville	North Carolina	United States	28803
44	Retina Associates of Cleveland	Cleveland	Ohio	United States	44130
45	Cleveland Clinic Foundation, Cole Eye Institute	Cleveland	Ohio	United States	44195
46	Retina Northwest	Portland	Oregon	United States	97210
47	Retina Consultants, LLC	Salem	Oregon	United States	97302
48	Cascade Medical Research Institute	Springfield	Oregon	United States	97477
49	MidAtlantic Retina	Philadelphia	Pennsylvania	United States	19107
50	Retina Research of Beaufort	Beaufort	South Carolina	United States	29902
51	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
52	Palmetto Retina Center	West Columbia	South Carolina	United States	296169
53	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
54	Southeastern Retina Associates PC	Knoxville	Tennessee	United States	37909
55	Tennessee Retina PC	Nashville	Tennessee	United States	37203
56	Retina Research Institute of Texas	Abilene	Texas	United States	79606
57	Austin Retina Associates	Austin	Texas	United States	78705
58	Retina Consultants of Texas	Houston	Texas	United States	77030
59	Retina Consultants of Texas-(Katy)	Katy	Texas	United States	77494
60	Texas Retina Associates	Plano	Texas	United States	75075
61	Austin Retina Associates (Round Rock)	Round Rock	Texas	United States	78681
62	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
63	Retina Consultants of Texas - (Woodlands)	The Woodlands	Texas	United States	77384
64	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
65	Spokane Eye	Spokane	Washington	United States	99204
66	Emanuelli Research & Development Center LLC	Arecibo		Puerto Rico	00612