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)
- Conditions
- Macular EdemaRetinal Vein Occlusion
- Interventions
- Registration Number
- NCT04592419
- Lead Sponsor
- Kodiak Sciences Inc
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 568
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aflibercept (Arm B) Sham Procedure 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. KSI-301 (Arm A) Sham Procedure 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. KSI-301 (Arm A) KSI-301 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. Aflibercept (Arm B) Aflibercept 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.
- Primary Outcome Measures
Name Time Method Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants. Day 1 to Week 24 BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients. Day 1 to Week 24 BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants. Baseline - Week 48 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.
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants. Day 1 - Week 48 Mean change in OCT center point retinal thickness (CPT) from baseline by visit over time (up to Week 48) for all RVO participants.
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants. Day 1 - Week 48 BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants. Day 1 - 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.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants. Baseline - Week 48 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.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants. Day 1 - Week 48. 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.
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants Day 1 - 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.
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants. Day 1 - Week 48 Mean change in OCT central subfield retinal thickness (CST) from baseline by visit over time (up to Week 48) for all RVO participants.
Trial Locations
- Locations (140)
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Vitreo Retinal Consultants and Surgeons
🇺🇸Wichita, Kansas, United States
Tennessee Retina PC
🇺🇸Nashville, Tennessee, United States
Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia
🇮🇹Udine, Italy
Retina Northwest
🇺🇸Portland, Oregon, United States
Northwest Arkansas Retina Associates
🇺🇸Phoenix, Arizona, United States
Retina Vitreous Associates
🇺🇸Beverly Hills, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
UCSD Jacobs Retina Center
🇺🇸La Jolla, California, United States
Retina Consultants of San Diego
🇺🇸Poway, California, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
Colorado Retina Associates PC
🇺🇸Lakewood, Colorado, United States
Orange County Retina Medical Group
🇺🇸Santa Ana, California, United States
California Retina Consultants
🇺🇸Santa Maria, California, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Florida Eye Clinic
🇺🇸Altamonte Springs, Florida, United States
Retina Group of Florida
🇺🇸Boca Raton, Florida, United States
Assuta HaShalom
🇮🇱Tel Aviv, Israel
Florida Eye Microsurgical Institute
🇺🇸Boynton Beach, Florida, United States
Rand Eye Institute
🇺🇸Deerfield Beach, Florida, United States
The Macula Center/ Blue Ocean Clinical Research
🇺🇸Clearwater, Florida, United States
Southern Vitreoretinal Associates
🇺🇸Tallahassee, Florida, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Fort Lauderdale Eye Institute
🇺🇸Plantation, Florida, United States
Center for Retina & Macular Disease
🇺🇸Winter Haven, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Talley Eye
🇺🇸Evansville, Indiana, United States
Retina Associates PA
🇺🇸Lenexa, Kansas, United States
Retina Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
Cumberland Valley Retina Consultants PC
🇺🇸Hagerstown, Maryland, United States
Foundation for Vision Research
🇺🇸Grand Rapids, Michigan, United States
Retina Consultants of NV
🇺🇸Henderson, Nevada, United States
Associated Retinal Consultants PC
🇺🇸Royal Oak, Michigan, United States
Vitreo Retinal Consultants
🇺🇸Hauppauge, New York, United States
Retina-Vitreous Surgeons of Central NY
🇺🇸Liverpool, New York, United States
Ocli Vision
🇺🇸Oceanside, New York, United States
Charlotte Eye Ear Nose & Throat Associates, P.A.
🇺🇸Charlotte, North Carolina, United States
Retina Associates of Cleveland
🇺🇸Cleveland, Ohio, United States
Cascade Medical Research Institute
🇺🇸Springfield, Oregon, United States
Charleston Neuroscience Institute
🇺🇸Ladson, South Carolina, United States
Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
Pametto Retina Center
🇺🇸West Columbia, South Carolina, United States
Southeastern Retina Associates PC
🇺🇸Knoxville, Tennessee, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Retina Consultants of Texas
🇺🇸Houston, Texas, United States
Austin Retina Associates (Round Rock)
🇺🇸Round Rock, Texas, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Retina Consultants of Texas - (Woodlands)
🇺🇸The Woodlands, Texas, United States
Strategic Clinical Research Group, LLC
🇺🇸Willow Park, Texas, United States
Retina Center Northwest
🇺🇸Silverdale, Washington, United States
Spokane Eye
🇺🇸Spokane, Washington, United States
OFTEX s.r.o.
🇨🇿Pardubice, Czechia
Vseobecna Fakultni
🇨🇿Praha, Czechia
Lekarna BENU
🇨🇿Praha, Czechia
Hôpital de La Croix Rousse
🇫🇷Lyon, Rhône, France
CHRU Dijon Complexe Du Bocage
🇫🇷Dijon, Côte-d'Or, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, France
Hôpital Lariboisière - Service Pharmacie
🇫🇷Paris, France
Centre Paradis Monticelli
🇫🇷Marseille, France
CHRU de Poitiers La Miletrie
🇫🇷Poitiers, France
Fondation Rothschild
🇫🇷Paris, France
Universitätsklinikum Regensburg
🇩🇪Regensburg, Bayern, Germany
St. Elisabeth Krankenhaus
🇩🇪Köln, Nordrhein-Westfalen, Germany
MH EK Honvedkorhaz SzemEszeti Osztaly
🇭🇺Budapest, Hungary
Miriam Kannenbaeumer or Andrea Koschinski
🇩🇪Münster, Nordrhein-Westfalen, Germany
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Bajcsy-Zsilinszky Korhaz es Rendelointezet
🇭🇺Budapest, Hungary
Bnai Zion
🇮🇱Haifa, Israel
Kaplan MC
🇮🇱Rehovot, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Shamir Medical Center Assaf Harofeh
🇮🇱Tzrifin, Israel
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
Signes Ozolinas Doctor Praxis In Ophthalmology
🇱🇻Jelgava, Latvia
Pauls Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Optimum Profesorskie Centrum Okulistyki
🇵🇱Gdansk, Pomorskie, Poland
Gabinet Okulistyczny Prof. Edward Wylegala
🇵🇱Katowice, Slaskie, Poland
Oftalmika Sp. z o.o.
🇵🇱Bydgoszcz, Poland
Dr Nowosielska Okulistyka i Chirurgia Oka
🇵🇱Warszawa, Poland
Emanuelli Research & Development Center LLC
🇵🇷Arecibo, Puerto Rico
Fakultna nemocnica Trencin
🇸🇰Trencín, Slovakia
Fakultna nemocnica s poliklinikou F. D. Roosevelta
🇸🇰Banská Bystrica, Slovakia
Uvea Klinika, S.R.O.
🇸🇰Martin, Slovakia
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital dos de Maig
🇪🇸Barcelona, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Rio Hortega
🇪🇸Valladolid, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Retina Associates of Florida
🇺🇸Tampa, Florida, United States
Retina Associates of Western NY
🇺🇸Rochester, New York, United States
Eye Medical Center of Fresno
🇺🇸Fresno, California, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
Retina Consultants, LLC
🇺🇸Salem, Oregon, United States
Retina Consultants of Texas - (Katy)
🇺🇸Katy, Texas, United States
Springfield Clinic LLP
🇺🇸Springfield, Illinois, United States
Vitreo Retinal Associates PC
🇺🇸Worcester, Massachusetts, United States
Vitreoretinal Surgery PA
🇺🇸Edina, Minnesota, United States
Asheville Eye Associates
🇺🇸Asheville, North Carolina, United States
The Retina Center of New Jersey
🇺🇸Bloomfield, New Jersey, United States
Retina Research of Beaufort
🇺🇸Beaufort, South Carolina, United States
Retina Consultants of Carolina
🇺🇸Greenville, South Carolina, United States
Texas Retina Associates
🇺🇸Plano, Texas, United States
Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
🇫🇷Bordeaux, Gironde, France
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Ospedale San Raffaele S.r.l. - PPDS
🇮🇹Milano, Lombardia, Italy
Univerzitna nemocnica Bratislava
🇸🇰Bratislava, Slovakia
Instituto Clinico Quirurgico de Oftalmologia
🇪🇸Bilbao, Spain
Meir MC
🇮🇱Kfar Saba, Israel
Budapest Retina Associates Kft
🇭🇺Budapest, Hungary
Jahn Ferenc Dél-Pesti Kórház és Rendelointézet
🇭🇺Budapest, Hungary
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
Conneticut Eye Consultants
🇺🇸Danbury, Connecticut, United States
NJ Retina
🇺🇸Teaneck, New Jersey, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Rambam MC
🇮🇱Haifa, Israel
Nemocnica s poliklinikou Trebisov a.s.
🇸🇰Trebišov, Slovakia
Maine Eye Center
🇺🇸Portland, Maine, United States
Hospital Universitari General de Catalunya - Grupo Quironsalud
🇪🇸Sant Cugat Del Vallès, Barcelona, Spain
Dietrich Bonhoeffer Klinikum Neubrandenburg
🇩🇪Neubrandenburg, Mecklenburg-Vorpommern, Germany
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Fondazione PTV Policlinico Tor Vergata
🇮🇹Roma, Lazio, Italy
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wrocław, Poland
Riga Eastern Clinical University Hospital Clinic Bikernieki
🇱🇻Riga, Latvia
Ospedale Clinicizzato SS Annunziata
🇮🇹Chieti, Abruzzo, Italy
Latvian American Eye Center
🇱🇻Riga, Latvia
Hospital Universitario de Bellvitge
🇪🇸L'hospitalet de Llobregat, Barcelona, Spain
Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
🇵🇱Katowice, Slaskie, Poland
Retinal Consultants Medical Group Inc
🇺🇸Sacramento, California, United States
Florida Retina Institute
🇺🇸Orlando, Florida, United States
Vitreo Retinal Associates
🇺🇸Gainesville, Florida, United States
Austin Research Center for Retina
🇺🇸Austin, Texas, United States
Retina Research Center
🇺🇸Austin, Texas, United States
Retina Institute of Virginia
🇺🇸Richmond, Virginia, United States