A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 in Participants With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR)
- Conditions
- Non-proliferative Diabetic Retinopathy
- Interventions
- Other: Sham injection
- Registration Number
- NCT05066230
- Lead Sponsor
- Kodiak Sciences Inc
- Brief Summary
This Phase 3 Study will evaluate the efficacy and safety of KSI-301 in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
- Detailed Description
This is a Phase 3, prospective, randomized, double-masked, sham-controlled, two-arm, multicenter study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
The primary endpoint will be assessed at Week 48; additional secondary endpoints for efficacy will be assessed at Week 48, Week 96 and if applicable, over time.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 253
- Signed informed consent prior to participation in the study.
- Type 1 or 2 diabetes mellitus
- Moderately severe to severe NPDR in the Study Eye (DRSS levels 47 and 53 as determined by the reading center), in which pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator.
- BCVA ETDRS letter score in the Study Eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
- HbA1c of ≤12%.
- Other protocol-specified inclusion criteria may apply.
- Presence of center-involved DME in the Study Eye
- Prior PRP in the Study Eye.
- Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye.
- Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME.
- Prior intravitreal or periocular steroid in the Study Eye for DR or DME.
- Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye.
- Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or alter visual acuity during the study
- Active or suspected ocular or periocular infection or inflammation.
- Women who are pregnant or lactating or intending to become pregnant during the study.
- 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.
- 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.
- Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥ 100 mmHg while at rest.
- Other protocol-specified exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Group B Sham injection Sham injection on the same schedule as Treatment Group A KSI-301 - Treatment Group A KSI-301 Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92
- Primary Outcome Measures
Name Time Method Percentage of Patients Improving ≥2 Steps on DRSS Day 1 to Week 48 Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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).
- Secondary Outcome Measures
Name Time Method Percentage of Patients Developing Any Sight-Threatening Complication Day 1 to Week 48 Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48
Percentage of Patients Improving ≥3 Steps on DRSS Day 1 to Week 48 Percentage of patients improving ≥3 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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 Developing PDR Day 1 to Week 48 Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48
Percentage of Patients Developing PDR or ASNV Day 1 to Week 48 Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) from baseline through Week 48
Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR Day 1 to Week 48 Percentage of patients developing vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48
Percentage of Patients Developing DME Day 1 to Week 48 Percentage of patients developing Diabetic Macular Edema (DME) from baseline through Week 48
Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS Day 1 to Week 48 Percentage of patients with a ≥2-step or ≥3-step worsening on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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 Who Lost ≥5, ≥10, or ≥15 Letters in BCVA Day 1 to Week 48 Percentage of patients who lost ≥5, ≥10, or ≥15 letters in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. 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.
Time to First Development of PDR, ASNV, or DME Day 1 to Week 48 Time to first development of Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), or Diabetic Macular Edema (DME) through Week 48
Time to First Development of PDR or ASNV Day 1 to Week 48 Time to first development of Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) through Week 48
Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR Day 1 to Week 48 Time to first development of vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) through Week 48
Trial Locations
- Locations (61)
Charleston Neurosciences Institute
🇺🇸Beaufort, South Carolina, United States
Retina Specialists of Idaho
🇺🇸Boise, Idaho, United States
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Med Eye Associates
🇺🇸Miami, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Springfield Clinic LLP
🇺🇸Springfield, Illinois, United States
MidAtlantic Retina
🇺🇸Bethlehem, Pennsylvania, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Retina Consultants of San Antonio
🇺🇸San Antonio, Texas, United States
Tennessee Retina PC
🇺🇸Nashville, Tennessee, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Retina Associates PA
🇺🇸Lenexa, Kansas, United States
Ophthalmic Consultants of Long Island
🇺🇸Oceanside, New York, United States
Latvian American Eye Center
🇱🇻Rīga, Latvia
Connecticut Eye Consultants
🇺🇸Danbury, Connecticut, United States
Foundation for Vision Research
🇺🇸Grand Rapids, Michigan, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Center for Retina & Macular Disease
🇺🇸Winter Haven, Florida, United States
Envision Ocular LLC
🇺🇸Bloomfield, New Jersey, United States
The Macula Center/ Blue Ocean Clinical Research
🇺🇸Clearwater, Florida, United States
Retina Group of Florida
🇺🇸Fort Lauderdale, Florida, United States
Cumberland Valley Retina Consultants PC
🇺🇸Hagerstown, Maryland, United States
Pauls Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Optimum Profesorskie Centrum Okulistyki
🇵🇱Gdansk, Pomorskie, Poland
Southeastern Retina Associates PC
🇺🇸Knoxville, Tennessee, United States
Charles Retina Institute
🇺🇸Memphis, Tennessee, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
Fakultna nemocnica s poliklinikou F. D. Roosevelta
🇸🇰Banska Bystrica, Slovakia
Fakultna nemocnica Trencin
🇸🇰Trencin, Slovakia
Charleston Neuroscience Center
🇺🇸Charleston, South Carolina, United States
Cascade Medical Research Institute
🇺🇸Eugene, Oregon, United States
Warszawski Szpital Okulistyczny
🇵🇱Warszawa, Mazowieckie, Poland
Oftalmika Sp. z o.o.
🇵🇱Bydgoszcz, Poland
Emanuelli Research & Development Center LLC
🇵🇷Arecibo, Puerto Rico
Hospital Universitario de Bellvitge
🇪🇸L'hospitalet de Llobregat, Barcelona, Spain
Hospital Universitari General de Catalunya - Grupo Quironsalud
🇪🇸Sant Cugat del Valles, Barcelona, Spain
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
California Retina Consultants - Santa Maria
🇺🇸Santa Maria, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Retina Vitreous Associates
🇺🇸Beverly Hills, California, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Graystone Eye
🇺🇸Hickory, North Carolina, United States
Long Island Vitreoretinal Consultants
🇺🇸Hauppauge, New York, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Retina Consultants of Texas (Katy)
🇺🇸Katy, Texas, United States
Austin Retina Associates (Round Rock)
🇺🇸Round Rock, Texas, United States
Retina Consultants of Texas (Houston)
🇺🇸Bellaire, Texas, United States
Panhandle Eye Group, LLP
🇺🇸Amarillo, Texas, United States
Star Vision Consultants
🇺🇸Burleson, Texas, United States
Texas Retina Associates
🇺🇸Plano, Texas, United States
Retina Consultants of Texas - (Woodlands)
🇺🇸The Woodlands, Texas, United States
OFTEX s.r.o.
🇨🇿Pardubice, Pardubický Kraj, Czechia
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Axon Clinical, s.r.o.
🇨🇿Praha 5, Czechia
Spokane Eye
🇺🇸Spokane, Washington, United States
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Madrid, Majadanonda, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Retinal Consultants Medical Group Inc
🇺🇸Sacramento, California, United States
Florida Retina Institute
🇺🇸Orlando, Florida, United States