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

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): 459
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Pardubice, Czechia, 53002
    • Oftex s.r.o.
  • Praha, Czechia, 128 08
    • Vseobecna Fakultni
  • Praha, Czechia, 150 00
    • Lekarna BENU
• France
  • Créteil, France, 94000
    • Centre Hospitalier Intercommunal de Creteil
  • Marseille, France, 13008
    • Centre Paradis Monticelli
  • Paris, France, 75019
    • Fondation Rothschild
  • Paris, France, 75 010
    • Hôpital Lariboisière - Service Pharmacie , Essais cliniques - Aude Jacob
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • CHRU Dijon Complexe Du Bocage
  • Rhône
    • Lyon, Rhône, France, 69317
      • Hôpital de la Croix Rousse
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Kórház és Rendelőintézet
  • Budapest, Hungary, 1133
    • Budapest Retina Associates Kft
  • Szabolcs-Szatmár-Bereg
    • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, H-4400
      • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz , Josa Andras Oktatókórház
• Israel
  • Haifa, Israel, 31096
    • Rambam MC
  • Haifa, Israel, 31048
    • Bnai Zion
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital
  • Kfar Saba, Israel, 44281
    • Meir MC
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Rehovot, Israel, 76100
    • Kaplan MC
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
  • Tel Aviv, Israel, 6789140
    • Assuta HaShalom
  • Tzrifin, Israel, 70300
    • Shamir Medical Center Assaf Harofeh
• Italy
  • Naples, Italy, 80131
    • AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele S.r.l. - PPDS
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Sp. z o.o.
  • Warszawa, Poland, 01-249
    • Dr Nowosielska Okulistyka i Chirurgia Oka
  • Wałbrzych, Poland, 58-309
    • Specjalistyczny Szpital im. Alfreda Sokolowskiego
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-809
      • Optimum Profesorskie Centrum Okulistyki
  • Slaskie
    • Katowice, Slaskie, Poland, 40-514
      • Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research & Development Center LLC
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Research Institute, LLC
  • California
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Poway, California, United States, 92064
      • Retina Consultants of San Diego
    • Sacramento, California, United States, 95825
      • Retinal Consultants Medical Group Inc
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Institute
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye Institute
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Plantation, Florida, United States, 33324
      • Fort Lauderdale Eye Institute
    • Saint Petersburg, Florida, United States, 33703
      • Retina Vitreous Associates of Florida
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Associates
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina, P.C.
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Retina Consultants of Hawaii, Inc
  • Idaho
    • Boise, Idaho, United States, 83713
      • Retina Specialists of Idaho
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Talley Eye
  • Maine
    • Portland, Maine, United States, 04101
      • Maine Eye Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants PC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Vitreoretinal Surgery PA
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Retina Consultants of NV
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New York
    • Hauppauge, New York, United States, 11788
      • Vitreo Retinal Consultants
    • Liverpool, New York, United States, 13088
      • Retina-Vitreous Surgeons of Central NY
    • Oceanside, New York, United States, 11572
      • Ophthalmic Consultants of Long Island
    • Rochester, New York, United States, 14620
      • Retina Associates of Western NY
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Eye Associates
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation, Cole Eye Institute
  • Oregon
    • Salem, Oregon, United States, 97302
      • Retina Consultants, LLC
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78705
      • Austin Research Center for Retina
    • Fort Worth, Texas, United States, 76108
      • Texas Retina Associates
    • Katy, Texas, United States, 77494
      • Retina Consultants of Houston-(Katy)
    • Plano, Texas, United States, 75075
      • Texas Retina Associates
    • Round Rock, Texas, United States, 78681
      • Austin Retina Associates (Round Rock)
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston - (Woodlands)
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia

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 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
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P105	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).	Day 1 to Week 52
Mean Change in OCT CST	Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) 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): April 27, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 27, 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: KS301P105; 2020-001063-82 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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