A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 in Non-proliferative Diabetic Retinopathy (NPDR) (GLOW)

A Prospective, Randomized, Double-masked, Sham-controlled, Multicenter, Two-arm Phase3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 in Participants With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy

This Phase 3 Study will evaluate the efficacy and safety of KSI-301 in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).

Study Overview

• Status: Terminated
• Conditions: Non-proliferative Diabetic Retinopathy
• Intervention / Treatment: Drug: KSI-301; Other: Sham injection

Detailed Description

This is a Phase 3, prospective, randomized, double-masked, sham-controlled, two-arm, multicenter study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).

The primary endpoint will be assessed at Week 48; additional secondary endpoints for efficacy will be assessed at Week 48, Week 96 and if applicable, over time.

• Study Type: Interventional
• Enrollment (Actual): 253
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Praha 5, Czechia, 15 0 00
    • Axon Clinical, s.r.o.
  • Pardubický Kraj
    • Pardubice, Pardubický Kraj, Czechia, 530 02
      • Oftex s.r.o.
• Latvia
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
  • Rīga, Latvia, LV-1009
    • Latvian American Eye Center
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Sp. z o.o.
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-258
      • Warszawski Szpital Okulistyczny
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-952
      • Optimum Profesorskie Centrum Okulistyki
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research & Development Center LLC
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna nemocnica s poliklinikou F. D. Roosevelta
  • Trencin, Slovakia, 911 71
    • Fakultna nemocnica Trencin
• Spain
  • Zaragoza, Spain, 50001
    • Hospital Clinico Universitario Lozano Blesa
  • Zaragoza, Spain, 50006
    • Hospital Universitario Miguel Servet
  • Barcelona
    • L'hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
    • Sant Cugat del Valles, Barcelona, Spain, 08195
      • Hospital Universitari General de Catalunya - Grupo Quirónsalud
  • Majadanonda
    • Madrid, Majadanonda, Spain, 28220
      • Hospital Universitario Puerta de Hierro - Majadahonda
• 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
    • Redlands, California, United States, 92374
      • Retina Consultants of Southern California
    • Sacramento, California, United States, 95825
      • Retinal Consultants Medical Group Inc
    • Santa Maria, California, United States, 93454
      • California Retina Consultants - Santa Maria
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Connecticut Eye Consultants
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Clearwater, Florida, United States, 33761
      • The Macula Center/ Blue Ocean Clinical Research
    • Fort Lauderdale, Florida, United States, 33308
      • Retina Group of Florida
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Miami, Florida, United States, 33143
      • Med Eye Associates
    • Orlando, Florida, United States, 32806
      • Florida Retina Institute
    • Winter Haven, Florida, United States, 33880
      • Center for Retina & Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Idaho
    • Boise, Idaho, United States, 83713
      • Retina Specialists of Idaho
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic LLP
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates PA
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants PC
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Foundation for Vision Research
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular LLC
  • New York
    • Hauppauge, New York, United States, 11788
      • Long Island Vitreoretinal Consultants
    • Oceanside, New York, United States, 11572
      • Ophthalmic Consultants of Long Island
  • North Carolina
    • Hickory, North Carolina, United States, 28603-2588
      • Graystone Eye
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Cascade Medical Research Institute
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017-9412
      • MidAtlantic Retina
  • South Carolina
    • Beaufort, South Carolina, United States, 29902
      • Charleston Neurosciences Institute
    • Charleston, South Carolina, United States, 29414
      • Charleston Neuroscience Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Southeastern Retina Associates PC
    • Memphis, Tennessee, United States, 38119-4823
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Amarillo, Texas, United States, 79106
      • Panhandle Eye Group, LLP
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas (Houston)
    • Burleson, Texas, United States, 76028
      • Star Vision Consultants
    • Katy, Texas, United States, 77494
      • Retina Consultants of Texas (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
    • San Antonio, Texas, United States, 78240
      • Retina Consultants of San Antonio
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas - (Woodlands)
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
  • Washington
    • 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:

• Signed informed consent prior to participation in the study.
• Type 1 or 2 diabetes mellitus
• Moderately severe to severe NPDR in the Study Eye (DRSS levels 47 and 53 as determined by the reading center), in which pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator.
• BCVA ETDRS letter score in the Study Eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
• HbA1c of ≤12%.
• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

• Presence of center-involved DME in the Study Eye
• Prior PRP in the Study Eye.
• Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye.
• Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME.
• Prior intravitreal or periocular steroid in the Study Eye for DR or DME.
• Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye.
• Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or alter visual acuity during the study
• Active or suspected ocular or periocular infection or inflammation.
• Women who are pregnant or lactating or intending to become pregnant during the study.
• 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.
• 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.
• Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥ 100 mmHg while at rest.
• 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 - Treatment Group A; Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92	Drug: KSI-301; Intravitreal injection
Sham Comparator: Treatment Group B; Sham injection on the same schedule as Treatment Group A	Other: Sham injection; The sham injection 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 is performed to maintain masking of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Improving ≥2 Steps on DRSS	Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Developing Any Sight-Threatening Complication	Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48	Day 1 to Week 48
Percentage of Patients Improving ≥3 Steps on DRSS	Percentage of patients improving ≥3 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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 48
Percentage of Patients Developing PDR	Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48	Day 1 to Week 48
Percentage of Patients Developing PDR or ASNV	Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) from baseline through Week 48	Day 1 to Week 48
Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR	Percentage of patients developing vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48	Day 1 to Week 48
Percentage of Patients Developing DME	Percentage of patients developing Diabetic Macular Edema (DME) from baseline through Week 48	Day 1 to Week 48
Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS	Percentage of patients with a ≥2-step or ≥3-step worsening on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). 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 48
Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA	Percentage of patients who lost ≥5, ≥10, or ≥15 letters in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. 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 48
Time to First Development of PDR, ASNV, or DME	Time to first development of Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), or Diabetic Macular Edema (DME) through Week 48	Day 1 to Week 48
Time to First Development of PDR or ASNV	Time to first development of Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) through Week 48	Day 1 to Week 48
Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR	Time to first development of vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) through Week 48	Day 1 to Week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Development of DME	Time to first development of Diabetic Macular Edema (DME) through Week 48	Day 1 to Week 48
Mean Change in OCT CST	Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline by visit over time	Day 1 to Week 48
Mean Change in BCVA	Mean change in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. 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 48

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Actual): August 3, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: VEGF; Eye Diseases; NPDR; Diabetic Retinopathy; Retinal Diseases; Retinopathy; Non-proliferative Diabetic Retinopathy; Anti-VEGF; Retinal Degeneration; Vascular Endothelial Growth Factor; KSI-301; Kodiak; Vision Disorders; Antibody Biopolymer Conjugate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: KS301P106

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