A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) (GLEAM)

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)

This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.

Study Overview

• Status: Terminated
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Aflibercept; Drug: KSI-301; Other: Sham Procedure

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.

• Study Type: Interventional
• Enrollment (Actual): 460
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • Universitatsklinikum Freiburg
  • Bayern
    • Regensburg, Bayern, Germany, 93053
      • Universitätsklinikum Regensburg
  • Mecklenburg-Vorpommern
    • Neubrandenburg, Mecklenburg-Vorpommern, Germany, 17036
      • Dietrich Bonhoeffer Klinikum Neubrandenburg
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50935
      • St. Elisabeth Krankenhaus
    • Münster, Nordrhein-Westfalen, Germany, 48145
      • St Franziskus Hospital
• Hungary
  • Budapest, Hungary, 1214
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
  • Pécs, Hungary, 7621
    • Ganglion Medical Center
• Italy
  • Roma, Italy, 00133
    • Fondazione Ptv Policlinico Tor Vergata
• Latvia
  • Jelgava, Latvia, LV-3001
    • Signes Ozolinas Doctor Praxis in Ophthalmology
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, LV-1006
    • Riga Eastern Clinical University Hospital Clinic Bikernieki
  • Riga, Latvia, LV-1009
    • Latvian American Eye Center
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research & Development Center LLC
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • Fakultna nemocnica s poliklinikou F. D. Roosevelta
  • Bratislava, Slovakia, 826 06
    • Univerzitna nemocnica Bratislava
  • Martin, Slovakia, 036 01
    • Uvea Klinika, S.R.O.
  • Trebišov, Slovakia, 075 01
    • Nemocnica s poliklinikou Trebisov a.s. Ocne oddelenie - jednonova zdravotna starostlivost
  • Trencín, Slovakia, 911 01
    • Fakultna nemocnica Trencin
  • Žilina, Slovakia, 012 07
    • Fakultna nemocnica s poliklinikou Zilina
• Spain
  • Barcelona, Spain, 08028
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08025
    • Hospital Dos de Maig
  • Barcelona, Spain, 08195
    • Hospital Universitari General de Catalunya - Grupo Quirónsalud
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Valladolid, Spain, 47012
    • Hospital Universitario Rio Hortega
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• United States
  • California
    • La Jolla, California, United States, 92037
      • UCSD Jacobs Retina Center
    • Redlands, California, United States, 92374
      • Retina Consultants of Southern California
    • Santa Maria, California, United States, 93454
      • California Retina Consultants
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Retina Associates PC
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Conneticut Eye Consultants
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Retina Group of Florida
    • Clearwater, Florida, United States, 33761
      • Blue Ocean Clinical Research
    • Gainesville, Florida, United States, 32607
      • Vitreo Retinal Associates
    • Lakeland, Florida, United States, 33805
      • Florida Retina Consultants
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Orlando, Florida, United States, 32806
      • Florida Retina Institute
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida
    • Tampa, Florida, United States, 33617
      • Retina Vitreous Associates of Florida
    • Winter Haven, Florida, United States, 33880
      • Center for Retina & Macular Disease
  • Illinois
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic LLP
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates PA
    • Wichita, Kansas, United States, 67214
      • Vitreo Retinal Consultants and Surgeons
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Foundation for Vision Research
  • New Jersey
    • Bloomfield, New Jersey, United States, 07017
      • The Retina Center of New Jersey
    • Teaneck, New Jersey, United States, 07605
      • NJ Retina
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose & Throat Associates, P.A.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Retina Northwest
    • Springfield, Oregon, United States, 97477
      • Cascade Medical Research Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • MidAtlantic Retina
  • South Carolina
    • Beaufort, South Carolina, United States, 29902
      • Retina Research of Beaufort
    • Charleston, South Carolina, United States, 29414
      • Charleston Neuroscience Institute - West Ashley
    • Florence, South Carolina, United States, 29501
      • Pametto Retina Center
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience Institute
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Amarillo, Texas, United States, 79106
      • Southwest Retina Specialists
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Burleson, Texas, United States, 76028
      • Star Retina
    • Houston, Texas, United States, 77030
      • Retina Consultants of Texas
    • San Antonio, Texas, United States, 78240
      • Retina Consultants of San Antonio
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group, LLC
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
  • Washington
    • Silverdale, Washington, United States, 98383
      • Retina Center Northwest
    • Spokane, Washington, United States, 99204
      • Spokane Eye

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KSI-301 (Arm A); 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.	Drug: KSI-301; Intravitreal Injection; Other: Sham Procedure; The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Active Comparator: Aflibercept (Arm B); 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.	Drug: Aflibercept; Intravitreal Injection; Other Names: Eylea; Other: Sham Procedure; The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in BCVA	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.	Day 1 to Week 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined	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).	Day 1 to Week 52
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104	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).	Day 1 to Week 52
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval	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.	Week 56
Mean Number of Intravitreal Injections	Mean number of intravitreal injections from Day 1 to Week 60	Day 1 to Week 60
Mean Change in OCT CST	Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline to the average of Weeks 60 and 64	Day 1 to Week 64

Collaborators and Investigators

• Sponsor: Kodiak Sciences Inc
• Investigators: Study Director: Pablo Velazquez-Martin, MD, Kodiak Sciences Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): May 11, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): November 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; VEGF; Eye Diseases; Eylea; Diabetes mellitus; Vascular endothelial growth factor; Aflibercept; Diabetic macular edema; Macular edema; Diabetic retinopathy; Retinal Diseases; Anti-VEGF; DME; Retinal Degeneration; KSI-301; Kodiak; Antibody biopolymer conjugate; Vision Disorders; Vision, low
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: KS301P104; 2020-001062-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No