GLIMMER: A Study 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

NCT04603937

Collaborator

(none)

459

Enrollment

Locations

Arms

Anticipated Duration (Months)

5.2

Patients Per Site

0.1

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 :

459 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 :

Apr 1, 2023

Anticipated Study Completion Date :

Feb 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

Non-inferiority of KSI-301 to Aflibercept measured by changes in BCVA. [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]
Improvement 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]
Improvement in central subfield thickness (CST).
Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in DRSS. [Day 1 to Year 2]
Improvement if the 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	Retinal Research Institute, LLC	Phoenix	Arizona	United States	85014
2	Northwest Arkansas Retina Associates	Springdale	Arkansas	United States	72762
3	Retina Vitreous Associates	Beverly Hills	California	United States	90211
4	Eye Medical Center of Fresno	Fresno	California	United States	93720
5	Retina Consultants of Orange County	Fullerton	California	United States	92835
6	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
7	Retina Consultants of San Diego	Poway	California	United States	92064
8	Retina Consultants of Southern California	Redlands	California	United States	92374
9	Retinal Consultants Medical Group Inc	Sacramento	California	United States	95819
10	Southwest Eye Consultants	Durango	Colorado	United States	81301
11	Colorado Retina Associates PC	Lakewood	Colorado	United States	80228
12	Connecticut Eye Consultants	Danbury	Connecticut	United States	06810
13	Retina Group of New England	Waterford	Connecticut	United States	06385
14	Florida Eye Clinic	Altamonte Springs	Florida	United States	32701
15	Retina Group of Florida	Boca Raton	Florida	United States	33431
16	Florida Eye Microsurgical Institute	Boynton Beach	Florida	United States	33426
17	Rand Eye Institute	Deerfield Beach	Florida	United States	33064
18	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
19	Med Eye Associates	Miami	Florida	United States	33143
20	Fort Lauderdale Eye Institute	Plantation	Florida	United States	33324
21	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33703
22	Southern Vitreoretinal Associates	Tallahassee	Florida	United States	32308
23	Southeast Retina Center	Augusta	Georgia	United States	30909
24	Georgia Retina, P.C.	Marietta	Georgia	United States	30060
25	Retina Consultants of Hawaii, Inc	'Aiea	Hawaii	United States	96701
26	Retina Specialists of Idaho	Boise	Idaho	United States	83713
27	Talley Eye	Evansville	Indiana	United States	47710
28	Maine Eye Center	Portland	Maine	United States	04102
29	Retina Group of Washington	Chevy Chase	Maryland	United States	20815
30	New England Retina Consultants	Springfield	Massachusetts	United States	01103
31	Associated Retinal Consultants PC	Royal Oak	Michigan	United States	78073
32	Vitreoretinal Surgery PA	Edina	Minnesota	United States	55435
33	Retina Consultants of NV	Henderson	Nevada	United States	89052
34	Sierra Eye Associates	Reno	Nevada	United States	89502
35	NJ Retina	Teaneck	New Jersey	United States	07605
36	Vitreo Retinal Consultants	Great Neck	New York	United States	11021
37	Retina-Vitreous Surgeons of Central NY	Liverpool	New York	United States	13088
38	Ophthalmic Consultants of Long Island	Oceanside	New York	United States	11572
39	Retina Associates of Western NY	Rochester	New York	United States	14620
40	Asheville Eye Associates	Asheville	North Carolina	United States	28803
41	Cleveland Clinic Foundation, Cole Eye Institute	Cleveland	Ohio	United States	44195
42	Retina Consultants, LLC	Salem	Oregon	United States	97302
43	Retina Consultants of Carolina	Greenville	South Carolina	United States	29605
44	Southeastern Retina Associates PC	Knoxville	Tennessee	United States	37909
45	Retina Research Institute of Texas	Abilene	Texas	United States	79606
46	Austin Research Center for Retina	Austin	Texas	United States	78705
47	Retina Consultants of Houston-(Katy)	Katy	Texas	United States	77494
48	Texas Retina Associates	Plano	Texas	United States	75075
49	Austin Retina Associates (Round Rock)	Round Rock	Texas	United States	78681
50	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
51	Retina Consultants of Houston - (Woodlands)	The Woodlands	Texas	United States	77384
52	Retina Institute of Virginia	Richmond	Virginia	United States	23235
53	Vitreoretinal Associates of Washington	Bellevue	Washington	United States	98004
54	Retina Center Northwest	Silverdale	Washington	United States	98383
55	OFTEX s.r.o.	Pardubice		Czechia	53002
56	Vseobecna Fakultni	Praha		Czechia	128 08
57	Lekarna BENU	Praha		Czechia	150 00
58	CHRU Dijon Complexe Du Bocage	Dijon	Côte-d'Or	France	21079
59	Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin	Bordeaux	Gironde	France	33076
60	Hôpital de La Croix Rousse	Lyon	Rhône	France	69317
61	Centre Hospitalier Intercommunal de Créteil	Créteil		France	94000
62	Centre Paradis Monticelli	Marseille		France	13008
63	Fondation Rothschild	Paris		France	75019
64	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz , Josa Andras Oktatókórház	Nyíregyháza	Szabolcs-Szatmár-Bereg	Hungary	H-4400
65	Semmelweis Egyetem	Budapest		Hungary	1085
66	Bajcsy-Zsilinszky Korhaz es Rendelointezet	Budapest		Hungary	1106
67	Budapest Retina Associates Kft	Budapest		Hungary	1133
68	Bnai Zion	Haifa		Israel	31048
69	Rambam MC	Haifa		Israel	31096
70	Hadassah University Hospital	Jerusalem		Israel	91120
71	Meir MC	Kfar Saba		Israel	44281
72	Rabin Medical Center	Petach Tikva		Israel	49100
73	Kaplan MC	Rehovot		Israel	76100
74	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
75	Assuta HaShalom	Tel Aviv		Israel	6789140
76	Shamir Medical Center Assaf Harofeh	Tzrifin		Israel	70300
77	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio	Italy	00168
78	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia	Italy	20132
79	AOU dell'Università degli Studi della Campania Luigi Vanvitelli	Naples		Italy	80131
80	Optimum Profesorskie Centrum Okulistyki	Gdansk	Pomorskie	Poland	80-809
81	Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi	Katowice	Slaskie	Poland	40-514
82	Gabinet Okulistyczny Prof. Edward Wylegala	Katowice	Slaskie	Poland	40-594
83	Oftalmika Sp. z o.o.	Bydgoszcz		Poland	85-631
84	Gabinet Okulistyczny prof. E. Wylegala	Katowice		Poland	40-760
85	Dr Nowosielska Okulistyka i Chirurgia Oka	Warszawa		Poland	01-249
86	Specjalistyczny Szpital im. Alfreda Sokolowskiego	Wałbrzych		Poland	58-309
87	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wrocław		Poland	50-556
88	Emanuelli Research & Development Center LLC	Arecibo		Puerto Rico	00612