Clinical trial NCT04592419: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Edema
Retinal Vein Occlusion
Keywords: RVO
Kodiak
KSI-301
Vascular endothelial growth factor
Anti-VEGF
VEGF
Antibody biopolymer conjugate
Retinal Degeneration
Retinal Diseases
Eye Diseases
Vision Disorders
Vision, low
Aflibercept
Eylea
Lead sponsor: Kodiak Sciences Inc
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 568
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.
timeFrame: Day 1 to Week 24
measure: Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.
timeFrame: Day 1 to Week 24
Secondary outcomes:
measure: Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.
timeFrame: Day 1 - Week 48
measure: Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.
timeFrame: Day 1 - Week 48
measure: Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants
timeFrame: Day 1 - Week 48
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants.
timeFrame: Day 1 - Week 48.
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants.
timeFrame: Baseline - Week 48
measure: Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants.
timeFrame: Baseline - Week 48
measure: Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants.
timeFrame: Day 1 - Week 48
measure: Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants.
timeFrame: Day 1 - Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Northwest Arkansas Retina Associates
state: Arizona
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates
state: California
city: Fresno
country: United States
facility: Eye Medical Center of Fresno
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: La Jolla
country: United States
facility: UCSD Jacobs Retina Center
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates
state: California
city: Poway
country: United States
facility: Retina Consultants of San Diego
state: California
city: Redlands
country: United States
facility: Retina Consultants of Southern California
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group Inc
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Medical Group
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants
state: California
city: Lakewood
country: United States
facility: Colorado Retina Associates PC
state: Colorado
city: Danbury
country: United States
facility: Conneticut Eye Consultants
state: Connecticut
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Altamonte Springs
country: United States
facility: Florida Eye Clinic
state: Florida
city: Boca Raton
country: United States
facility: Retina Group of Florida
state: Florida
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Institute
state: Florida
city: Clearwater
country: United States
facility: The Macula Center/ Blue Ocean Clinical Research
state: Florida
city: Deerfield Beach
country: United States
facility: Rand Eye Institute
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Gainesville
country: United States
facility: Vitreo Retinal Associates
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Associates
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina & Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Springfield
country: United States
facility: Springfield Clinic LLP
state: Illinois
city: Evansville
country: United States
facility: Talley Eye
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lenexa
country: United States
facility: Retina Associates PA
state: Kansas
city: Wichita
country: United States
facility: Vitreo Retinal Consultants and Surgeons
state: Kansas
city: Lexington
country: United States
facility: Retina Associates of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants PC
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Worcester
country: United States
facility: Vitreo Retinal Associates PC
state: Massachusetts
city: Grand Rapids
country: United States
facility: Foundation for Vision Research
state: Michigan
city: Royal Oak
country: United States
facility: Associated Retinal Consultants PC
state: Michigan
city: Edina
country: United States
facility: Vitreoretinal Surgery PA
state: Minnesota
city: Henderson
country: United States
facility: Retina Consultants of NV
state: Nevada
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: The Retina Center of New Jersey
state: New Jersey
city: Teaneck
country: United States
facility: NJ Retina
state: New Jersey
city: Hauppauge
country: United States
facility: Vitreo Retinal Consultants
state: New York
city: Liverpool
country: United States
facility: Retina-Vitreous Surgeons of Central NY
state: New York
city: Oceanside
country: United States
facility: Ocli Vision
state: New York
city: Rochester
country: United States
facility: Retina Associates of Western NY
state: New York
city: Asheville
country: United States
facility: Asheville Eye Associates
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose & Throat Associates, P.A.
state: North Carolina
city: Beachwood
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Salem
country: United States
facility: Retina Consultants, LLC
state: Oregon
city: Springfield
country: United States
facility: Cascade Medical Research Institute
state: Oregon
city: Beaufort
country: United States
facility: Retina Research of Beaufort
state: South Carolina
city: Greenville
country: United States
facility: Retina Consultants of Carolina
state: South Carolina
city: Ladson
country: United States
facility: Charleston Neuroscience Institute
state: South Carolina
city: West Columbia
country: United States
facility: Pametto Retina Center
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates PC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina PC
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Research Center for Retina
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Katy
country: United States
facility: Retina Consultants of Texas - (Katy)
state: Texas
city: Plano
country: United States
facility: Texas Retina Associates
state: Texas
city: Round Rock
country: United States
facility: Austin Retina Associates (Round Rock)
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas - (Woodlands)
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
state: Texas
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
city: Silverdale
country: United States
facility: Retina Center Northwest
state: Washington
city: Spokane
country: United States
facility: Spokane Eye
state: Washington
city: Pardubice
country: Czechia
facility: OFTEX s.r.o.
city: Praha
country: Czechia
facility: Vseobecna Fakultni
city: Praha
country: Czechia
facility: Lekarna BENU
city: Dijon
country: France
facility: CHRU Dijon Complexe Du Bocage
state: Côte-d'Or
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
state: Gironde
city: Lyon
country: France
facility: Hôpital de La Croix Rousse
state: Rhône
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Marseille
country: France
facility: Centre Paradis Monticelli
city: Paris
country: France
facility: Hôpital Lariboisière - Service Pharmacie
city: Paris
country: France
facility: Fondation Rothschild
city: Poitiers
country: France
facility: CHRU de Poitiers La Miletrie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
state: Bayern
city: Neubrandenburg
country: Germany
facility: Dietrich Bonhoeffer Klinikum Neubrandenburg
state: Mecklenburg-Vorpommern
city: Köln
country: Germany
facility: St. Elisabeth Krankenhaus
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Miriam Kannenbaeumer or Andrea Koschinski
state: Nordrhein-Westfalen
city: Budapest
country: Hungary
facility: MH EK Honvedkorhaz SzemEszeti Osztaly
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Budapest Retina Associates Kft
city: Budapest
country: Hungary
facility: Jahn Ferenc Dél-Pesti Kórház és Rendelointézet
city: Haifa
country: Israel
facility: Bnai Zion
city: Haifa
country: Israel
facility: Rambam MC
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Kfar Saba
country: Israel
facility: Meir MC
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan MC
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta HaShalom
city: Tzrifin
country: Israel
facility: Shamir Medical Center Assaf Harofeh
city: Chieti
country: Italy
facility: Ospedale Clinicizzato SS Annunziata
state: Abruzzo
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia
city: Jelgava
country: Latvia
facility: Signes Ozolinas Doctor Praxis In Ophthalmology
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Riga Eastern Clinical University Hospital Clinic Bikernieki
city: Riga
country: Latvia
facility: Latvian American Eye Center
city: Gdansk
country: Poland
facility: Optimum Profesorskie Centrum Okulistyki
state: Pomorskie
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
state: Slaskie
city: Katowice
country: Poland
facility: Gabinet Okulistyczny Prof. Edward Wylegala
state: Slaskie
city: Bydgoszcz
country: Poland
facility: Oftalmika Sp. z o.o.
city: Warszawa
country: Poland
facility: Dr Nowosielska Okulistyka i Chirurgia Oka
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research & Development Center LLC
city: Banská Bystrica
country: Slovakia
facility: Fakultna nemocnica s poliklinikou F. D. Roosevelta
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava
city: Martin
country: Slovakia
facility: Uvea Klinika, S.R.O.
city: Trebišov
country: Slovakia
facility: Nemocnica s poliklinikou Trebisov a.s.
city: Trencín
country: Slovakia
facility: Fakultna nemocnica Trencin
city: L'hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya - Grupo Quironsalud
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital dos de Maig
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Bilbao
country: Spain
facility: Instituto Clinico Quirurgico de Oftalmologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Kodiak Sciences Inc
name: Pablo Velazquez-Martin, MD
role: STUDY_DIRECTOR
References: