BEACON: A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO)

Sponsor

Kodiak Sciences Inc (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04592419

Collaborator

(none)

568

Enrollment

141

Locations

Arms

33.1

Anticipated Duration (Months)

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 macular edema due to treatment-naïve branch (BRVO) or central retinal vein occlusion (CRVO).

Condition or Disease	Intervention/Treatment	Phase
Macular Edema Retinal Vein Occlusion	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 macular edema secondary to RVO (either branch or central type).

The primary endpoint will be assessed at Week 24; additional secondary endpoints for efficacy will be assessed at Week 24 and Week 48.

This includes an optional open-label, two-arm, double-masked Extension Phase in which participants completing the primary BEACON study are eligible to participate. All participants who enroll into the Extension Phase will be treated with KSI-301 5 mg. The Extension Phase will have the final study assessment at Week 72 for efficacy endpoints and a final safety follow-up at Week 76.

Study Design

Study Type:

Interventional

Actual Enrollment :

568 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 in the Extension Phase will be treated with KSI-301.Participants will be randomized 1:1 into one of two treatment arms: KSI-301 or aflibercept. Participants in the Extension Phase will be treated with KSI-301.

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 Due to Treatment-naïve Macular Edema Secondary to Retinal Vein Occlusion (RVO)

Actual Study Start Date :

Sep 25, 2020

Actual Primary Completion Date :

Jun 20, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KSI-301 (Arm A) Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.	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 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.	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) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.

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 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.

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 Week 24]
Demonstrate that KSI-301 5 mg administered every 8 weeks after 2 monthly doses is non-inferior to aflibercept 2 mg monthly 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 and CST. [Day 1 to Week 44]
Improvement in best corrected visual acuity (BCVA) and central subfield thickness (CST) between the two treatment arms.
Durability of KSI-301 5 mg compared to aflibercept 2 mg based on number of intravitreal injections during the study. [Week 1 to Week 44]
Mean number of intravitreal injections during the course of the study 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 76]
Incidence of ocular and systemic adverse events up to Week 24, Week 52, and Week 76

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 macular edema of 6 months duration or less due to CRVO or BRVO. Participants with hemiretinal vein occlusion will be included as CRVO.
BCVA ETDRS letter score between 80 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 ME secondary to RVO.
Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

Macular edema in the Study Eye for reasons other than RVO
Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.
Uncontrolled glaucoma 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 alter visual acuity during the study
Active or suspected ocular or periocular infection or inflammation
Any prior use of an approved or investigational treatment for macular edema secondary to RVO 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	Northwest Arkansas Retina Associates	Phoenix	Arizona	United States	85014
2	Retinal Research Institute, LLC	Phoenix	Arizona	United States	85014
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	UCSD Jacobs Retina Center	La Jolla	California	United States	92037
7	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
8	Retina Consultants of San Diego	Poway	California	United States	92064
9	Retina Consultants of Southern California	Redlands	California	United States	92374
10	Retinal Consultants Medical Group Inc	Sacramento	California	United States	95819
11	Orange County Retina Medical Group	Santa Ana	California	United States	92705
12	California Retina Consultants	Santa Maria	California	United States	93454
13	Colorado Retina Associates PC	Lakewood	Colorado	United States	80228
14	Conneticut Eye Consultants	Danbury	Connecticut	United States	06810
15	Retina Group of New England	Waterford	Connecticut	United States	06385
16	Florida Eye Clinic	Altamonte Springs	Florida	United States	32701
17	Retina Group of Florida	Boca Raton	Florida	United States	33431
18	Florida Eye Microsurgical Institute	Boynton Beach	Florida	United States	33426
19	The Macula Center/ Blue Ocean Clinical Research	Clearwater	Florida	United States	33761
20	Rand Eye Institute	Deerfield Beach	Florida	United States	33064
21	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
22	Vitreo Retinal Associates	Gainesville	Florida	United States	32607
23	Florida Eye Associates	Melbourne	Florida	United States	32901
24	Florida Retina Institute	Orlando	Florida	United States	32806
25	Retina Specialty Institute	Pensacola	Florida	United States	32503
26	Fort Lauderdale Eye Institute	Plantation	Florida	United States	33324
27	Southern Vitreoretinal Associates	Tallahassee	Florida	United States	32308
28	Retina Associates of Florida	Tampa	Florida	United States	33609
29	Center for Retina & Macular Disease	Winter Haven	Florida	United States	33880
30	Southeast Retina Center	Augusta	Georgia	United States	30909
31	Springfield Clinic LLP	Springfield	Illinois	United States	62703
32	Talley Eye	Evansville	Indiana	United States	47710
33	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
34	Retina Associates PA	Lenexa	Kansas	United States	66215
35	Vitreo Retinal Consultants and Surgeons	Wichita	Kansas	United States	67214
36	Retina Associates of Kentucky	Lexington	Kentucky	United States	40509
37	Maine Eye Center	Portland	Maine	United States	04102
38	Retina Group of Washington	Chevy Chase	Maryland	United States	20815
39	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland	United States	21740
40	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
41	Vitreo Retinal Associates PC	Worcester	Massachusetts	United States	01603
42	Foundation for Vision Research	Grand Rapids	Michigan	United States	49525
43	Associated Retinal Consultants PC	Royal Oak	Michigan	United States	78073
44	Vitreoretinal Surgery PA	Edina	Minnesota	United States	55435
45	Retina Consultants of NV	Henderson	Nevada	United States	89052
46	Sierra Eye Associates	Reno	Nevada	United States	89502
47	The Retina Center of New Jersey	Bloomfield	New Jersey	United States	07017
48	NJ Retina	Teaneck	New Jersey	United States	07605
49	Vitreo Retinal Consultants	Hauppauge	New York	United States	11788
50	Retina-Vitreous Surgeons of Central NY	Liverpool	New York	United States	13088
51	Ocli Vision	Oceanside	New York	United States	11572
52	Retina Associates of Western NY	Rochester	New York	United States	14620
53	Asheville Eye Associates	Asheville	North Carolina	United States	28803
54	Charlotte Eye Ear Nose & Throat Associates, P.A.	Charlotte	North Carolina	United States	28210
55	Retina Associates of Cleveland	Beachwood	Ohio	United States	44122
56	Retina Associates of Cleveland	Cleveland	Ohio	United States	44130
57	Retina Northwest	Portland	Oregon	United States	97210
58	Retina Consultants, LLC	Salem	Oregon	United States	97302
59	Cascade Medical Research Institute	Springfield	Oregon	United States	97477
60	Retina Research of Beaufort	Beaufort	South Carolina	United States	29902
61	Retina Consultants of Carolina	Greenville	South Carolina	United States	29605
62	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
63	Pametto Retina Center	West Columbia	South Carolina	United States	29501
64	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
65	Charles Retina Institute	Germantown	Tennessee	United States	38138
66	Southeastern Retina Associates PC	Knoxville	Tennessee	United States	37909
67	Tennessee Retina PC	Nashville	Tennessee	United States	37203
68	Retina Research Institute of Texas	Abilene	Texas	United States	79606
69	Austin Research Center for Retina	Austin	Texas	United States	78705
70	Austin Retina Associates	Austin	Texas	United States	78705
71	Retina Research Center	Austin	Texas	United States	78705
72	Retina Consultants of Texas	Houston	Texas	United States	77030
73	Retina Consultants of Texas - (Katy)	Katy	Texas	United States	77494
74	Texas Retina Associates	Plano	Texas	United States	75075
75	Austin Retina Associates (Round Rock)	Round Rock	Texas	United States	78681
76	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
77	Retina Consultants of Texas - (Woodlands)	The Woodlands	Texas	United States	77384
78	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
79	Retina Institute of Virginia	Richmond	Virginia	United States	23235
80	Retina Center Northwest	Silverdale	Washington	United States	98383
81	Spokane Eye	Spokane	Washington	United States	99204
82	OFTEX s.r.o.	Pardubice		Czechia	53002
83	Vseobecna Fakultni	Praha		Czechia	128 08
84	Lekarna BENU	Praha		Czechia	150 00
85	CHRU Dijon Complexe Du Bocage	Dijon	Côte-d'Or	France	21079
86	Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin	Bordeaux	Gironde	France	33076
87	Hôpital de La Croix Rousse	Lyon	Rhône	France	69317
88	Centre Hospitalier Intercommunal de Créteil	Créteil		France	94000
89	Centre Paradis Monticelli	Marseille		France	13008
90	Hôpital Lariboisière - Service Pharmacie	Paris		France	75 010
91	Fondation Rothschild	Paris		France	75019
92	CHRU de Poitiers La Miletrie	Poitiers		France	86021
93	Universitätsklinikum Regensburg	Regensburg	Bayern	Germany	93053
94	Dietrich Bonhoeffer Klinikum Neubrandenburg	Neubrandenburg	Mecklenburg-Vorpommern	Germany	17036
95	St. Elisabeth Krankenhaus	Köln	Nordrhein-Westfalen	Germany	50935
96	Miriam Kannenbaeumer or Andrea Koschinski	Münster	Nordrhein-Westfalen	Germany	48145
97	MH EK Honvedkorhaz SzemEszeti Osztaly	Budapest		Hungary	1062
98	Semmelweis Egyetem	Budapest		Hungary	1085
99	Bajcsy-Zsilinszky Korhaz es Rendelointezet	Budapest		Hungary	1106
100	Budapest Retina Associates Kft	Budapest		Hungary	1133
101	Jahn Ferenc Dél-Pesti Kórház és Rendelointézet	Budapest		Hungary	1214
102	Bnai Zion	Haifa		Israel	31048
103	Rambam MC	Haifa		Israel	31096
104	Hadassah University Hospital	Jerusalem		Israel	91120
105	Meir MC	Kfar Saba		Israel	44281
106	Rabin Medical Center	Petach Tikva		Israel	49100
107	Kaplan MC	Rehovot		Israel	76100
108	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
109	Assuta HaShalom	Tel Aviv		Israel	6789140
110	Shamir Medical Center Assaf Harofeh	Tzrifin		Israel	70300
111	Ospedale Clinicizzato SS Annunziata	Chieti	Abruzzo	Italy	66100
112	Fondazione PTV Policlinico Tor Vergata	Roma	Lazio	Italy	00133
113	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio	Italy	00168
114	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia	Italy	20132
115	Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia	Udine		Italy	33100
116	Signes Ozolinas Doctor Praxis In Ophthalmology	Jelgava		Latvia	LV-3001
117	Pauls Stradins Clinical University Hospital	Riga		Latvia	LV-1002
118	Riga Eastern Clinical University Hospital Clinic Bikernieki	Riga		Latvia	LV-1006
119	Latvian American Eye Center	Riga		Latvia	LV-1009
120	Optimum Profesorskie Centrum Okulistyki	Gdansk	Pomorskie	Poland	80-809
121	Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi	Katowice	Slaskie	Poland	40-514
122	Gabinet Okulistyczny Prof. Edward Wylegala	Katowice	Slaskie	Poland	40-594
123	Oftalmika Sp. z o.o.	Bydgoszcz		Poland	85-631
124	Dr Nowosielska Okulistyka i Chirurgia Oka	Warszawa		Poland	01-249
125	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wrocław		Poland	50-556
126	Emanuelli Research & Development Center LLC	Arecibo		Puerto Rico	00612
127	Fakultna nemocnica s poliklinikou F. D. Roosevelta	Banská Bystrica		Slovakia	974 01
128	Univerzitna nemocnica Bratislava	Bratislava		Slovakia	826 06
129	Uvea Klinika, S.R.O.	Martin		Slovakia	036 01
130	Nemocnica s poliklinikou Trebisov a.s.	Trebišov		Slovakia	075 01
131	Fakultna nemocnica Trencin	Trencín		Slovakia	911 01
132	Hospital Universitario de Bellvitge	L'hospitalet de Llobregat	Barcelona	Spain	08907
133	Hospital Universitari General de Catalunya - Grupo Quironsalud	Sant Cugat Del Vallès	Barcelona	Spain	08195
134	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid	Spain	28222
135	Hospital dos de Maig	Barcelona		Spain	08025
136	Hospital Clinic de Barcelona	Barcelona		Spain	08028
137	Instituto Clinico Quirurgico de Oftalmologia	Bilbao		Spain	48010
138	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
139	Hospital Universitario Rio Hortega	Valladolid		Spain	47012
140	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
141	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009