Clinical trial NCT04603937: A Study 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: 2020-10-27
Enrollment: 459
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 KS301P105
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: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
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: Sacramento
country: United States
facility: Retinal Consultants Medical Group Inc
state: California
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Institute
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: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Associates
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina, P.C.
state: Georgia
city: 'Aiea
country: United States
facility: Retina Consultants of Hawaii, Inc
state: Hawaii
city: Boise
country: United States
facility: Retina Specialists of Idaho
state: Idaho
city: Evansville
country: United States
facility: Talley Eye
state: Indiana
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Royal Oak
country: United States
facility: Associated Retinal Consultants PC
state: Michigan
city: Minneapolis
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: 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: Ophthalmic Consultants of Long Island
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: Cleveland
country: United States
facility: Cleveland Clinic Foundation, Cole Eye Institute
state: Ohio
city: Salem
country: United States
facility: Retina Consultants, LLC
state: Oregon
city: Knoxville
country: United States
facility: Southeastern Retina Associates 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: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Katy
country: United States
facility: Retina Consultants of Houston-(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 Houston - (Woodlands)
state: Texas
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
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: 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 , Essais cliniques - Aude Jacob
city: Paris
country: France
facility: Fondation Rothschild
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz , Josa Andras Oktatókórház
state: Szabolcs-Szatmár-Bereg
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: 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: 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: Naples
country: Italy
facility: AOU dell'Università degli Studi della Campania Luigi Vanvitelli
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: Bydgoszcz
country: Poland
facility: Oftalmika Sp. z o.o.
city: Warszawa
country: Poland
facility: Dr Nowosielska Okulistyka i Chirurgia Oka
city: Wałbrzych
country: Poland
facility: Specjalistyczny Szpital im. Alfreda Sokolowskiego
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
Study officials:
affiliation: Kodiak Sciences Inc
name: Pablo Velazquez-Martin, MD
role: STUDY_DIRECTOR
References: