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

Sponsor

Kodiak Sciences Inc (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04611152

Collaborator

(none)

460

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	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 treatment-naïve DME.

The primary endpoint will be assessed at Year 1; additional secondary endpoints for efficacy will be assessed at Years 1 and 2.

Study Design

Study Type:

Interventional

Actual Enrollment :

460 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 Visual Impairment Secondary to Treatment-naïve Diabetic Macular Edema (DME)

Actual Study Start Date :

Sep 30, 2020

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: KSI-301 Intravitreal Injection 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.
Active Comparator: 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.	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 (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.

Drug: KSI-301

Intravitreal Injection

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.

Active Comparator: 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.

Drug: Aflibercept

Intravitreal Injection

Other Names:

Eylea

Other: Sham Procedure

Outcome Measures

Primary Outcome Measures

Changes in BCVA to Assess Non-inferiority of KSI-301 to Aflibercept. [Day 1 to Year 1]
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 measured by changes in BCVA. [Day 1 to Year 2]
Change in best corrected visual acuity (BCVA).
Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in CST. [Day 1 to Year 2]
Change in central subfield thickness (CST).
Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in the diabetic retinopathy severity score (DRSS). [Day 1 to Year 2]
Change in diabetic retinopathy severity score (DRSS).
Durability of KSI-301 5 mg compared to aflibercept 2 mg measured by number of intravitreal injections during the study. [Day 1 to Year 2]
Mean number of intravitreal injections during the course of the study.
Safety and Tolerability of KSI-301 mg compared to aflibercept 2 mg measured by the number of ocular and systemic adverse events. [Day 1 to Year 2]
Incidence of ocular and systemic adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent prior to participation in the study.
Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening.
BCVA ETDRS letter score between 78 and 25 (-20/25 to 20/320 Snellen equivalent), inclusive, in the Study Eye.
CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center.
Decrease in vision determined by the Investigator to be primarily the result of DME.
Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%.
Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

Macular edema in the Study Eye considered to be secondary to a cause other than DME.
Active iris or angle neovascularization or neovascular glaucoma in the Study Eye.
High-risk proliferative diabetic retinopathy characteristics in the Study Eye.
History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening.
Tractional retinal detachment in the Study Eye.
Active retinal disease other than the condition under investigation in the Study Eye.
Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention or affect macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal membrane).
Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
Any prior use of an approved or investigational treatment for DME in the Study Eye (e.g., anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).
Women who are pregnant or lactating or intending to become pregnant during the study.
Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest.
Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event.
History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
Other protocol-specified exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Retina Consultants	Bakersfield	California	United States	93309
2	UCSD Jacobs Retina Center	La Jolla	California	United States	92037
3	Retina Associates of Orange County	Laguna Hills	California	United States	92653
4	Stanford Byers Eye Institute	Palo Alto	California	United States	94303
5	Retina Consultants of Southern California	Redlands	California	United States	92374
6	California Retina Consultants	Santa Maria	California	United States	93454
7	Colorado Retina Associates PC	Lakewood	Colorado	United States	80228
8	Conneticut Eye Consultants	Danbury	Connecticut	United States	06810
9	Retina Group of Florida	Boca Raton	Florida	United States	33431
10	Vitreo Retinal Associates	Gainesville	Florida	United States	32607
11	Florida Eye Associates	Melbourne	Florida	United States	32901
12	Florida Retina Institute	Orlando	Florida	United States	32806
13	Retina Specialty Institute	Pensacola	Florida	United States	32503
14	Retina Associates of Florida	Tampa	Florida	United States	33609
15	Center for Retina & Macular Disease	Winter Haven	Florida	United States	33880
16	Rush University Medical Center	Chicago	Illinois	United States	60612
17	Springfield Clinic LLP	Springfield	Illinois	United States	62703
18	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
19	Retina Associates PA	Lenexa	Kansas	United States	66215
20	Retina Associates of Kentucky	Lexington	Kentucky	United States	40509
21	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland	United States	21740
22	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
23	Vitreo Retinal Associates PC	Worcester	Massachusetts	United States	01603
24	Foundation for Vision Research	Grand Rapids	Michigan	United States	49525
25	The Retina Center of New Jersey	Bloomfield	New Jersey	United States	07017
26	NJ Retina	Teaneck	New Jersey	United States	07605
27	Charlotte Eye Ear Nose & Throat Associates, P.A.	Charlotte	North Carolina	United States	28210
28	Retina Associates of Cleveland	Cleveland	Ohio	United States	44130
29	Retina Northwest	Portland	Oregon	United States	97210
30	Cascade Medical Research Institute	Springfield	Oregon	United States	97477
31	MidAtlantic Retina	Philadelphia	Pennsylvania	United States	19107
32	Retina Research of Beaufort	Beaufort	South Carolina	United States	29902
33	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
34	Pametto Retina Center	West Columbia	South Carolina	United States	29501
35	Palmetto Retina Center	West Columbia	South Carolina	United States	296169
36	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
37	Tennessee Retina PC	Nashville	Tennessee	United States	37203
38	Austin Retina Associates	Austin	Texas	United States	78705
39	Retina Consultants of Houston	Houston	Texas	United States	77030
40	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
41	Retina Center Northwest	Silverdale	Washington	United States	98383
42	Spokane Eye	Spokane	Washington	United States	99204
43	Signes Ozolinas Doctor Praxis In Ophthalmology	Jelgava		Latvia	LV-3001
44	Pauls Stradins Clinical University Hospital	Riga		Latvia	LV-1002
45	Riga Eastern Clinical University Hospital Clinic Bikernieki	Riga		Latvia	LV-1006
46	Latvian American Eye Center	Riga		Latvia	LV-1009