A Study 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
- NCT04603937
- 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
- 459
- 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) 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. 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.
- 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 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).
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P105 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 KS301P105. 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 Number of Intravitreal Injections Day 1 to Week 60 Mean number of intravitreal injections from Day 1 to Week 60
Mean Change in OCT CST Day 1 to Week 64 Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) baseline to the average of Weeks 60 and 64
Trial Locations
- Locations (71)
Cleveland Clinic Foundation, Cole Eye Institute
🇺🇸Cleveland, Ohio, United States
CHRU Dijon Complexe Du Bocage
🇫🇷Dijon, Côte-d'Or, France
Retina Specialists of Idaho
🇺🇸Boise, Idaho, United States
Georgia Retina, P.C.
🇺🇸Marietta, Georgia, United States
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, France
Ospedale San Raffaele S.r.l. - PPDS
🇮🇹Milano, Lombardia, Italy
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Talley Eye
🇺🇸Evansville, Indiana, United States
Retina-Vitreous Surgeons of Central NY
🇺🇸Liverpool, New York, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
Retina Consultants of Hawaii, Inc
🇺🇸'Aiea, Hawaii, United States
Retina Vitreous Associates of Florida
🇺🇸Saint Petersburg, Florida, United States
Asheville Eye Associates
🇺🇸Asheville, North Carolina, United States
Southeastern Retina Associates PC
🇺🇸Knoxville, Tennessee, United States
Ophthalmic Consultants of Long Island
🇺🇸Oceanside, New York, United States
Associated Retinal Consultants PC
🇺🇸Royal Oak, Michigan, United States
Fondation Rothschild
🇫🇷Paris, France
Austin Retina Associates (Round Rock)
🇺🇸Round Rock, Texas, United States
Retina Consultants of Houston - (Woodlands)
🇺🇸The Woodlands, Texas, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Retina Consultants of NV
🇺🇸Henderson, Nevada, United States
Lekarna BENU
🇨🇿Praha, Czechia
OFTEX s.r.o.
🇨🇿Pardubice, Czechia
Bnai Zion
🇮🇱Haifa, Israel
Kaplan MC
🇮🇱Rehovot, Israel
Assuta HaShalom
🇮🇱Tel Aviv, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Rand Eye Institute
🇺🇸Deerfield Beach, Florida, United States
Vseobecna Fakultni
🇨🇿Praha, Czechia
AOU dell'Università degli Studi della Campania Luigi Vanvitelli
🇮🇹Naples, Italy
Centre Paradis Monticelli
🇫🇷Marseille, France
Rambam MC
🇮🇱Haifa, Israel
Meir MC
🇮🇱Kfar Saba, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Shamir Medical Center Assaf Harofeh
🇮🇱Tzrifin, Israel
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Retina Consultants of San Diego
🇺🇸Poway, California, United States
Retina Vitreous Associates
🇺🇸Beverly Hills, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Florida Eye Microsurgical Institute
🇺🇸Boynton Beach, Florida, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Fort Lauderdale Eye Institute
🇺🇸Plantation, Florida, United States
Vitreo Retinal Consultants
🇺🇸Hauppauge, New York, United States
Southern Vitreoretinal Associates
🇺🇸Tallahassee, Florida, United States
Maine Eye Center
🇺🇸Portland, Maine, United States
Retina Consultants, LLC
🇺🇸Salem, Oregon, United States
Retina Consultants of Houston-(Katy)
🇺🇸Katy, Texas, United States
Texas Retina Associates
🇺🇸Plano, Texas, United States
Hôpital Lariboisière - Service Pharmacie , Essais cliniques - Aude Jacob
🇫🇷Paris, France
Emanuelli Research & Development Center LLC
🇵🇷Arecibo, Puerto Rico
Hôpital de La Croix Rousse
🇫🇷Lyon, Rhône, France
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz , Josa Andras Oktatókórház
🇭🇺Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary
Optimum Profesorskie Centrum Okulistyki
🇵🇱Gdansk, Pomorskie, Poland
Oftalmika Sp. z o.o.
🇵🇱Bydgoszcz, Poland
Dr Nowosielska Okulistyka i Chirurgia Oka
🇵🇱Warszawa, Poland
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
🇵🇱Katowice, Slaskie, Poland
Specjalistyczny Szpital im. Alfreda Sokolowskiego
🇵🇱Wałbrzych, Poland
Bajcsy-Zsilinszky Korhaz es Rendelointezet
🇭🇺Budapest, Hungary
Budapest Retina Associates Kft
🇭🇺Budapest, Hungary
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wrocław, Poland
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
Retinal Consultants Medical Group Inc
🇺🇸Sacramento, California, United States
Austin Research Center for Retina
🇺🇸Austin, Texas, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Vitreoretinal Surgery PA
🇺🇸Minneapolis, Minnesota, United States
Retina Institute of Virginia
🇺🇸Richmond, Virginia, United States
Retina Associates of Western NY
🇺🇸Rochester, New York, United States