Clinical trial NCT04611152: A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)
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 Secondary to Treatment-naïve Diabetic Macular Edema (DME)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetic Macular Edema
Keywords: DME
Kodiak
Vascular endothelial growth factor
Anti-VEGF
VEGF
Antibody biopolymer conjugate
Retinal Degeneration
Retinal Diseases
Eye Diseases
Vision Disorders
Vision, low
Aflibercept
Eylea
Diabetes mellitus
Diabetes
Diabetic retinopathy
Diabetic macular edema
Macular edema
KSI-301
Lead sponsor: Kodiak Sciences Inc
Sponsor class: INDUSTRY
First posted: 2020-11-02
Enrollment: 460
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.
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 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.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent prior to participation in the study.
2. Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening.
3. BCVA ETDRS letter score between 78 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 DME.
6. Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%.
7. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

1. Macular edema in the Study Eye considered to be secondary to a cause other than DME.
2. Active iris or angle neovascularization or neovascular glaucoma in the Study Eye.
3. High-risk proliferative diabetic retinopathy characteristics in the Study Eye.
4. History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening.
5. Tractional retinal detachment in the Study Eye.
6. Active retinal disease other than the condition under investigation in the Study Eye.
7. 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).
8. Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
9. 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).
10. Women who are pregnant or lactating or intending to become pregnant during the study.
11. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest.
12. 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.
13. 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.
14. Other protocol-specified exclusion criteria may apply.

Primary outcomes:
measure: Mean Change in BCVA
timeFrame: Day 1 to Week 64
Secondary outcomes:
measure: Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined
timeFrame: Day 1 to Week 52
measure: Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104
timeFrame: Day 1 to Week 52
measure: Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval
timeFrame: Week 56
measure: Mean Number of Intravitreal Injections
timeFrame: Day 1 to Week 60
measure: Mean Change in OCT CST
timeFrame: Day 1 to Week 64
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Jacobs Retina Center
state: California
city: Redlands
country: United States
facility: Retina Consultants of Southern California
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
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: Boca Raton
country: United States
facility: Retina Group of Florida
state: Florida
city: Clearwater
country: United States
facility: Blue Ocean Clinical Research
state: Florida
city: Gainesville
country: United States
facility: Vitreo Retinal Associates
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
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: Tampa
country: United States
facility: Retina Associates of Florida
state: Florida
city: Tampa
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina & Macular Disease
state: Florida
city: Springfield
country: United States
facility: Springfield Clinic LLP
state: Illinois
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: 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: Grand Rapids
country: United States
facility: Foundation for Vision Research
state: Michigan
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: Charlotte
country: United States
facility: Charlotte Eye Ear Nose & Throat Associates, P.A.
state: North Carolina
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Springfield
country: United States
facility: Cascade Medical Research Institute
state: Oregon
city: Philadelphia
country: United States
facility: MidAtlantic Retina
state: Pennsylvania
city: Beaufort
country: United States
facility: Retina Research of Beaufort
state: South Carolina
city: Charleston
country: United States
facility: Charleston Neuroscience Institute - West Ashley
state: South Carolina
city: Florence
country: United States
facility: Pametto Retina Center
state: South Carolina
city: Ladson
country: United States
facility: Charleston Neuroscience Institute
state: South Carolina
city: West Columbia
country: United States
facility: Palmetto 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: Nashville
country: United States
facility: Tennessee Retina PC
state: Tennessee
city: Amarillo
country: United States
facility: Southwest Retina Specialists
state: Texas
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Burleson
country: United States
facility: Star Retina
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Texas
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of San Antonio
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
state: Texas
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Silverdale
country: United States
facility: Retina Center Northwest
state: Washington
city: Spokane
country: United States
facility: Spokane Eye
state: Washington
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
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: St Franziskus Hospital
state: Nordrhein-Westfalen
city: Budapest
country: Hungary
facility: Jahn Ferenc Dél-Pesti Kórház és Rendelointézet
city: Pécs
country: Hungary
facility: Ganglion Medical Center
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
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: 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. Ocne oddelenie - jednonova zdravotna starostlivost
city: Trencín
country: Slovakia
facility: Fakultna nemocnica Trencin
city: Žilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou Zilina
city: Barcelona
country: Spain
facility: Hospital dos de Maig
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari General de Catalunya - Grupo Quironsalud
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
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: