A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)
- Conditions
- Diabetic Macular Edema
- Interventions
- Registration Number
- NCT04611152
- 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 treatment-naïve DME.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 460
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KSI-301 (Arm A) KSI-301 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. KSI-301 (Arm A) Sham Procedure 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. Aflibercept (Arm B) Aflibercept 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. Aflibercept (Arm B) Sham Procedure 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.
- Primary Outcome Measures
Name Time Method Mean Change in BCVA Day 1 to Week 64 Mean change in best-corrected visual acuity (BCVA) from baseline to the average of Weeks 60 and 64 (using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters). Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
- Secondary Outcome Measures
Name Time Method Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104 Day 1 to Week 52 Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Study KS301P104. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval Week 56 Percentage of patients in the KSI-301 arm on a Q8W, Q12W, Q16W, Q20W, or Q24W treatment interval at the primary endpoint. Analyses include KSI-301 patients who completed a treatment interval from Week 56 onwards.
Mean Change in OCT CST Day 1 to Week 64 Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline to the average of Weeks 60 and 64
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined Day 1 to Week 52 Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Studies KS301P104 and KS301P105 combined. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Mean Number of Intravitreal Injections Day 1 to Week 60 Mean number of intravitreal injections from Day 1 to Week 60
Trial Locations
- Locations (75)
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
MidAtlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Retina Consultants of Texas
🇺🇸Houston, Texas, United States
Retina Consultants of San Antonio
🇺🇸San Antonio, Texas, United States
Tennessee Retina PC
🇺🇸Nashville, Tennessee, United States
Florida Retina Consultants
🇺🇸Lakeland, Florida, United States
California Retina Consultants
🇺🇸Santa Maria, California, United States
UCSD Jacobs Retina Center
🇺🇸La Jolla, California, United States
Fakultna nemocnica Trencin
🇸🇰Trencín, Slovakia
Hospital dos de Maig
🇪🇸Barcelona, Spain
Center for Retina & Macular Disease
🇺🇸Winter Haven, Florida, United States
Spokane Eye
🇺🇸Spokane, Washington, United States
Fondazione PTV Policlinico Tor Vergata
🇮🇹Roma, Italy
Emanuelli Research & Development Center LLC
🇵🇷Arecibo, Puerto Rico
Dietrich Bonhoeffer Klinikum Neubrandenburg
🇩🇪Neubrandenburg, Mecklenburg-Vorpommern, Germany
Pauls Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Fakultna nemocnica s poliklinikou Zilina
🇸🇰Žilina, Slovakia
Ganglion Medical Center
🇭🇺Pécs, Hungary
Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
Fakultna nemocnica s poliklinikou F. D. Roosevelta
🇸🇰Banská Bystrica, Slovakia
Uvea Klinika, S.R.O.
🇸🇰Martin, Slovakia
Jahn Ferenc Dél-Pesti Kórház és Rendelointézet
🇭🇺Budapest, Hungary
St. Elisabeth Krankenhaus
🇩🇪Köln, Nordrhein-Westfalen, Germany
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Signes Ozolinas Doctor Praxis In Ophthalmology
🇱🇻Jelgava, Latvia
Riga Eastern Clinical University Hospital Clinic Bikernieki
🇱🇻Riga, Latvia
Latvian American Eye Center
🇱🇻Riga, Latvia
Univerzitna nemocnica Bratislava
🇸🇰Bratislava, Slovakia
Universitätsklinikum Freiburg
🇩🇪Freiburg, Baden-Württemberg, Germany
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Universitätsklinikum Regensburg
🇩🇪Regensburg, Bayern, Germany
St Franziskus Hospital
🇩🇪Münster, Nordrhein-Westfalen, Germany
Nemocnica s poliklinikou Trebisov a.s. Ocne oddelenie - jednonova zdravotna starostlivost
🇸🇰Trebišov, Slovakia
Hospital Universitari General de Catalunya - Grupo Quironsalud
🇪🇸Barcelona, Spain
Retina Northwest
🇺🇸Portland, Oregon, United States
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Rio Hortega
🇪🇸Valladolid, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
Conneticut Eye Consultants
🇺🇸Danbury, Connecticut, United States
Colorado Retina Associates PC
🇺🇸Lakewood, Colorado, United States
Retina Group of Florida
🇺🇸Boca Raton, Florida, United States
Blue Ocean Clinical Research
🇺🇸Clearwater, Florida, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Springfield Clinic LLP
🇺🇸Springfield, Illinois, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Cumberland Valley Retina Consultants PC
🇺🇸Hagerstown, Maryland, United States
Retina Associates PA
🇺🇸Lenexa, Kansas, United States
Vitreo Retinal Consultants and Surgeons
🇺🇸Wichita, Kansas, United States
The Retina Center of New Jersey
🇺🇸Bloomfield, New Jersey, United States
Foundation for Vision Research
🇺🇸Grand Rapids, Michigan, United States
NJ Retina
🇺🇸Teaneck, New Jersey, United States
Charlotte Eye Ear Nose & Throat Associates, P.A.
🇺🇸Charlotte, North Carolina, United States
Cascade Medical Research Institute
🇺🇸Springfield, Oregon, United States
Retina Research of Beaufort
🇺🇸Beaufort, South Carolina, United States
Pametto Retina Center
🇺🇸Florence, South Carolina, United States
Charleston Neuroscience Institute
🇺🇸Ladson, South Carolina, United States
Palmetto Retina Center
🇺🇸West Columbia, South Carolina, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Texas Retina Associates
🇺🇸Arlington, Texas, United States
Southwest Retina Specialists
🇺🇸Amarillo, Texas, United States
Star Retina
🇺🇸Burleson, Texas, United States
Strategic Clinical Research Group, LLC
🇺🇸Willow Park, Texas, United States
Florida Retina Institute
🇺🇸Orlando, Florida, United States
Retina Associates of Florida
🇺🇸Tampa, Florida, United States
Retina Vitreous Associates of Florida
🇺🇸Tampa, Florida, United States
Charleston Neuroscience Institute - West Ashley
🇺🇸Charleston, South Carolina, United States
Vitreo Retinal Associates
🇺🇸Gainesville, Florida, United States
Retina Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Retina Center Northwest
🇺🇸Silverdale, Washington, United States