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) (BEACON)

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)

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).

Study Overview

• Status: Completed
• Conditions: Macular Edema; Retinal Vein Occlusion
• Intervention / Treatment: Drug: Aflibercept; Drug: KSI-301; Other: Sham Procedure

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.

• Study Type: Interventional
• Enrollment (Actual): 568
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Pardubice, Czechia, 53002
    • Oftex s.r.o.
  • Praha, Czechia, 128 08
    • Vseobecna Fakultni
  • Praha, Czechia, 150 00
    • Lekarna BENU
• France
  • Créteil, France, 94000
    • Centre Hospitalier Intercommunal de Creteil
  • Marseille, France, 13008
    • Centre Paradis Monticelli
  • Paris, France, 75019
    • Fondation Rothschild
  • Paris, France, 75 010
    • Hôpital Lariboisière - Service Pharmacie
  • Poitiers, France, 86021
    • CHRU de Poitiers La Miletrie
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • CHRU Dijon Complexe Du Bocage
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin
  • Rhône
    • Lyon, Rhône, France, 69317
      • Hôpital de la Croix Rousse
• Germany
  • Bayern
    • Regensburg, Bayern, Germany, 93053
      • Universitätsklinikum Regensburg
  • Mecklenburg-Vorpommern
    • Neubrandenburg, Mecklenburg-Vorpommern, Germany, 17036
      • Dietrich Bonhoeffer Klinikum Neubrandenburg
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50935
      • St. Elisabeth Krankenhaus
    • Münster, Nordrhein-Westfalen, Germany, 48145
      • Miriam Kannenbaeumer or Andrea Koschinski
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Kórház és Rendelőintézet
  • Budapest, Hungary, 1062
    • MH EK Honvedkorhaz SzemEszeti Osztaly
  • Budapest, Hungary, 1133
    • Budapest Retina Associates Kft
  • Budapest, Hungary, 1214
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
• Israel
  • Haifa, Israel, 31096
    • Rambam MC
  • Haifa, Israel, 31048
    • Bnai Zion
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital
  • Kfar Saba, Israel, 44281
    • Meir MC
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Rehovot, Israel, 76100
    • Kaplan MC
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
  • Tel Aviv, Israel, 6789140
    • Assuta HaShalom
  • Tzrifin, Israel, 70300
    • Shamir Medical Center Assaf Harofeh
• Italy
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66100
      • Ospedale Clinicizzato SS Annunziata
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli
    • Roma, Lazio, Italy, 00133
      • Fondazione PTV Policlinico Tor Vergata
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele S.r.l. - PPDS
• Latvia
  • Jelgava, Latvia, LV-3001
    • Signes Ozolinas Doctor Praxis in Ophthalmology
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, LV-1006
    • Riga Eastern Clinical University Hospital Clinic Bikernieki
  • Riga, Latvia, LV-1009
    • Latvian American Eye Center
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Sp. z o.o.
  • Warszawa, Poland, 01-249
    • Dr Nowosielska Okulistyka i Chirurgia Oka
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-809
      • Optimum Profesorskie Centrum Okulistyki
  • Slaskie
    • Katowice, Slaskie, Poland, 40-514
      • Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
    • Katowice, Slaskie, Poland, 40-594
      • Gabinet Okulistyczny Prof. Edward Wylegala
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research & Development Center LLC
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • Fakultna nemocnica s poliklinikou F. D. Roosevelta
  • Bratislava, Slovakia, 826 06
    • Univerzitna nemocnica Bratislava
  • Martin, Slovakia, 036 01
    • Uvea Klinika, S.R.O.
  • Trebišov, Slovakia, 075 01
    • Nemocnica s poliklinikou Trebisov a.s.
  • Trencín, Slovakia, 911 01
    • Fakultna nemocnica Trencin
• Spain
  • Barcelona, Spain, 08028
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08025
    • Hospital dos de maig
  • Bilbao, Spain, 48010
    • Instituto Clinico Quirurgico de Oftalmologia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Valladolid, Spain, 47012
    • Hospital Universitario Rio Hortega
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano Blesa
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • L'hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
    • Sant Cugat Del Vallès, Barcelona, Spain, 08195
      • Hospital Universitari General de Catalunya - Grupo Quirónsalud
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Research Institute, LLC
    • Phoenix, Arizona, United States, 85014
      • Northwest Arkansas Retina Associates
  • California
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates
    • Fresno, California, United States, 93720
      • Eye Medical Center of Fresno
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • La Jolla, California, United States, 92037
      • UCSD Jacobs Retina Center
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Poway, California, United States, 92064
      • Retina Consultants of San Diego
    • Redlands, California, United States, 92374
      • Retina Consultants of Southern California
    • Sacramento, California, United States, 95819
      • Retinal Consultants Medical Group Inc
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
    • Santa Maria, California, United States, 93454
      • California Retina Consultants
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Retina Associates PC
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Conneticut Eye Consultants
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Eye Clinic
    • Boca Raton, Florida, United States, 33431
      • Retina Group of Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Institute
    • Clearwater, Florida, United States, 33761
      • The Macula Center/ Blue Ocean Clinical Research
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye Institute
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Gainesville, Florida, United States, 32607
      • Vitreo Retinal Associates
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Orlando, Florida, United States, 32806
      • Florida Retina Institute
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Fort Lauderdale Eye Institute
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Associates
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida
    • Winter Haven, Florida, United States, 33880
      • Center for Retina & Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Illinois
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic LLP
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Talley Eye
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates PA
    • Wichita, Kansas, United States, 67214
      • Vitreo Retinal Consultants and Surgeons
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Eye Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Retina Group of Washington
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
    • Worcester, Massachusetts, United States, 01603
      • Vitreo Retinal Associates PC
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Foundation for Vision Research
    • Royal Oak, Michigan, United States, 78073
      • Associated Retinal Consultants PC
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Vitreoretinal Surgery PA
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Retina Consultants of NV
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07017
      • The Retina Center of New Jersey
    • Teaneck, New Jersey, United States, 07605
      • NJ Retina
  • New York
    • Hauppauge, New York, United States, 11788
      • Vitreo Retinal Consultants
    • Liverpool, New York, United States, 13088
      • Retina-Vitreous Surgeons of Central NY
    • Oceanside, New York, United States, 11572
      • OCLI Vision
    • Rochester, New York, United States, 14620
      • Retina Associates of Western NY
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Eye Associates
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose & Throat Associates, P.A.
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Retina Associates of Cleveland
    • Cleveland, Ohio, United States, 44130
      • Retina Associates of Cleveland
  • Oregon
    • Portland, Oregon, United States, 97210
      • Retina Northwest
    • Salem, Oregon, United States, 97302
      • Retina Consultants, LLC
    • Springfield, Oregon, United States, 97477
      • Cascade Medical Research Institute
  • South Carolina
    • Beaufort, South Carolina, United States, 29902
      • Retina Research of Beaufort
    • Greenville, South Carolina, United States, 29605
      • Retina Consultants of Carolina
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience Institute
    • West Columbia, South Carolina, United States, 29501
      • Pametto Retina Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Knoxville, Tennessee, United States, 37909
      • Southeastern Retina Associates PC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • Austin, Texas, United States, 78705
      • Austin Research Center for Retina
    • Houston, Texas, United States, 77030
      • Retina Consultants of Texas
    • Katy, Texas, United States, 77494
      • Retina Consultants of Texas - (Katy)
    • Plano, Texas, United States, 75075
      • Texas Retina Associates
    • Round Rock, Texas, United States, 78681
      • Austin Retina Associates (Round Rock)
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas - (Woodlands)
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group, LLC
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia
  • Washington
    • Silverdale, Washington, United States, 98383
      • Retina Center Northwest
    • Spokane, Washington, United States, 99204
      • Spokane Eye

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent prior to participation in the study.
2. 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.
3. BCVA ETDRS letter score between 80 and 25 (20/25 to 20/320 Snellen equivalent), inclusive in the Study Eye.
4. CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center
5. Decrease in vision determined by the Investigator to be primarily the result of ME secondary to RVO.
6. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

1. Macular edema in the Study Eye for reasons other than RVO
2. Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.
3. Uncontrolled glaucoma in the Study Eye.
4. Active retinal disease other than the condition under investigation in the Study Eye.
5. 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
6. Active or suspected ocular or periocular infection or inflammation
7. 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).
8. Women who are pregnant or lactating or intending to become pregnant during the study.
9. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest
10. 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.
11. 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.
12. Other protocol-specified exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 to Week 24
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 - Week 48
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.	Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100*n/N.	Day 1 - Week 48
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants	Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100*n/N.	Day 1 - Week 48
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants.	Percentage of participants with BCVA Snellen Equivalent of 20/40 or Better from Baseline to Week 48. Snellen Equivalent of 20/40 is 69 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100*n/N.	Day 1 - Week 48.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants.	Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse from Baseline to Week 48. Snellen Equivalent of 20/200 is 38 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100*n/N.	Baseline - Week 48
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants.	Macular Edema (ME) is assessed by optical coherence tomography (OCT) central subfield thickness (CST). A thickness of less than 325 microns is considered absence of ME. Proportion of participants with Absence of Macular Edema from Baseline to Week 48. Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100*n/N.	Baseline - Week 48
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants.	Mean change in OCT central subfield retinal thickness (CST) from baseline by visit over time (up to Week 48) for all RVO participants.	Day 1 - Week 48
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants.	Mean change in OCT center point retinal thickness (CPT) from baseline by visit over time (up to Week 48) for all RVO participants.	Day 1 - Week 48

Collaborators and Investigators

• Sponsor: Kodiak Sciences Inc
• Investigators: Study Director: Pablo Velazquez-Martin, MD, Kodiak Sciences Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Actual): June 10, 2022
• Study Completion (Actual): January 19, 2023

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: VEGF; Eye Diseases; Eylea; Vascular endothelial growth factor; Aflibercept; Retinal Diseases; Anti-VEGF; RVO; Retinal Degeneration; KSI-301; Kodiak; Antibody biopolymer conjugate; Vision Disorders; Vision, low
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: KS301P103; 2020-001061-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No