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Diabetic Macular EdemaPhase 3GLEAMNCT04611152

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

A Phase 3 study testing KSI-301 and Aflibercept in people with Diabetic Macular Edema, run by Kodiak Sciences Inc at 75 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetic Macular Edema
What is being tested?
KSI-301 and Aflibercept
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
460 participants
Where
75 sitesin 8 countries
Study dates
30 Sep 2020to 31 Aug 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

75 sites in 8 countries.

75 sites in 8 countries

United States48 sites

  • Southwest Retina Specialists

    Amarillo, Texas, 79106

  • Texas Retina Associates

    Arlington, Texas, 76012

  • Austin Retina Associates

    Austin, Texas, 78705

  • Retina Research of Beaufort

    Beaufort, South Carolina, 29902

  • The Retina Center of New Jersey

    Bloomfield, New Jersey, 07017

  • Retina Group of Florida

    Boca Raton, Florida, 33431

  • Ophthalmic Consultants of Boston

    Boston, Massachusetts, 02114

  • Star Retina

    Burleson, Texas, 76028

  • Charleston Neuroscience Institute - West Ashley

    Charleston, South Carolina, 29414

  • Charlotte Eye Ear Nose & Throat Associates, P.A.

    Charlotte, North Carolina, 28210

  • Blue Ocean Clinical Research

    Clearwater, Florida, 33761

  • Conneticut Eye Consultants

    Danbury, Connecticut, 06810

  • Pametto Retina Center

    Florence, South Carolina, 29501

  • Vitreo Retinal Associates

    Gainesville, Florida, 32607

  • Charles Retina Institute

    Germantown, Tennessee, 38138

  • Foundation for Vision Research

    Grand Rapids, Michigan, 49525

  • Cumberland Valley Retina Consultants PC

    Hagerstown, Maryland, 21740

  • Retina Consultants of Texas

    Houston, Texas, 77030

  • UCSD Jacobs Retina Center

    La Jolla, California, 92037

  • Charleston Neuroscience Institute

    Ladson, South Carolina, 29456

  • Florida Retina Consultants

    Lakeland, Florida, 33805

  • Colorado Retina Associates PC

    Lakewood, Colorado, 80228

  • Retina Associates PA

    Lenexa, Kansas, 66215

  • Retina Associates of Kentucky

    Lexington, Kentucky, 40509

  • Piedmont Eye Center

    Lynchburg, Virginia, 24502

  • Florida Eye Associates

    Melbourne, Florida, 32901

  • Tennessee Retina PC

    Nashville, Tennessee, 37203

  • Florida Retina Institute

    Orlando, Florida, 32806

  • Retina Specialty Institute

    Pensacola, Florida, 32503

  • MidAtlantic Retina

    Philadelphia, Pennsylvania, 19107

  • Retina Northwest

    Portland, Oregon, 97210

  • Black Hills Regional Eye Institute

    Rapid City, South Dakota, 57701

  • Retina Consultants of Southern California

    Redlands, California, 92374

  • Retina Consultants of San Antonio

    San Antonio, Texas, 78240

  • California Retina Consultants

    Santa Maria, California, 93454

  • Retina Center Northwest

    Silverdale, Washington, 98383

  • Spokane Eye

    Spokane, Washington, 99204

  • Springfield Clinic LLP

    Springfield, Illinois, 62703

  • Cascade Medical Research Institute

    Springfield, Oregon, 97477

  • Retina Associates of Florida

    Tampa, Florida, 33609

  • Retina Vitreous Associates of Florida

    Tampa, Florida, 33617

  • NJ Retina

    Teaneck, New Jersey, 07605

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • Palmetto Retina Center

    West Columbia, South Carolina, 29169

  • Wolfe Eye Clinic

    West Des Moines, Iowa, 50266

  • Vitreo Retinal Consultants and Surgeons

    Wichita, Kansas, 67214

  • Strategic Clinical Research Group, LLC

    Willow Park, Texas, 76087

  • Center for Retina & Macular Disease

    Winter Haven, Florida, 33880

Other trials in United States

Spain8 sites

  • Hospital dos de Maig

    Barcelona, 08025

  • Hospital Clinic de Barcelona

    Barcelona, 08028

  • Hospital Universitari General de Catalunya - Grupo Quironsalud

    Barcelona, 08195

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Madrid, 28222

  • Hospital Universitari i Politecnic La Fe de Valencia

    Valencia, 46026

  • Hospital Universitario Rio Hortega

    Valladolid, 47012

  • Hospital Clinico Universitario Lozano Blesa

    Zaragoza, 50009

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

Slovakia6 sites

  • Fakultna nemocnica s poliklinikou F. D. Roosevelta

    Banská Bystrica, 974 01

  • Univerzitna nemocnica Bratislava

    Bratislava, 826 06

  • Uvea Klinika, S.R.O.

    Martin, 036 01

  • Nemocnica s poliklinikou Trebisov a.s. Ocne oddelenie - jednonova zdravotna starostlivost

    Trebišov, 075 01

  • Fakultna nemocnica Trencin

    Trencín, 911 01

  • Fakultna nemocnica s poliklinikou Zilina

    Žilina, 012 07

Other trials in Slovakia

Germany5 sites

  • St. Elisabeth Krankenhaus

    Cologne, North Rhine-Westphalia, 50935

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • St Franziskus Hospital

    Münster, North Rhine-Westphalia, 48145

  • Dietrich Bonhoeffer Klinikum Neubrandenburg

    Neubrandenburg, Mecklenburg-Vorpommern, 17036

  • Universitätsklinikum Regensburg

    Regensburg, Bavaria, 93053

Other trials in Germany

Latvia4 sites

  • Signes Ozolinas Doctor Praxis In Ophthalmology

    Jelgava, LV-3001

  • Pauls Stradins Clinical University Hospital

    Riga, LV-1002

  • Riga Eastern Clinical University Hospital Clinic Bikernieki

    Riga, LV-1006

  • Latvian American Eye Center

    Riga, LV-1009

Other trials in Latvia

Hungary2 sites

  • Jahn Ferenc Dél-Pesti Kórház és Rendelointézet

    Budapest, 1214

  • Ganglion Medical Center

    Pécs, 7621

Other trials in Hungary

Italy1 site

  • Fondazione PTV Policlinico Tor Vergata

    Roma, 00133

Other trials in Italy

Puerto Rico1 site

  • Emanuelli Research & Development Center LLC

    Arecibo, 00612

Other trials in Puerto Rico

About this study

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)

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

Read the 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.

Being tested
KSI-301, Aflibercept, Sham Procedure
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
Medical subject headings
Retinal Degeneration, Retinal Diseases, Eye Diseases, Vision Disorders, Vision, Low, Diabetes Mellitus, Diabetic Retinopathy, Macular Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KSI-301Drug

    Intravitreal Injection

  • AfliberceptDrug

    Also called Eylea

    Intravitreal Injection

  • Sham ProcedureOther

    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.

Study groups in NCT04611152
Study groupRoleWhat they receive
KSI-301 (Arm A)ExperimentalIntravitreal 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.
Receives: Drug: KSI-301; Other: Sham Procedure
Aflibercept (Arm B)Active comparatorIntravitreal 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.
Receives: Drug: Aflibercept; Other: Sham Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 1 to Week 64

Secondary outcomes (5)

  1. 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).

    Measured: Day 1 to Week 52

  2. 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).

    Measured: Day 1 to Week 52

  3. 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.

    Measured: Week 56

  4. Mean Number of Intravitreal Injections

    Mean number of intravitreal injections from Day 1 to Week 60

    Measured: Day 1 to Week 60

  5. 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

    Measured: Day 1 to Week 64

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2020
  2. Study start30 Sep 2020
  3. Primary completion11 May 2023
  4. Study completion31 Aug 2023

Why it stopped: Study did not meet primary endpoint

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomized 1:1 into one of two treatment arms: KSI-301 or aflibercept.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
460 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04611152
Sponsor's protocol ID
KS301P104
Other IDs
2020-001062-11
Acronym
GLEAM
Status last verified
Aug 2024
First submitted
19 Oct 2020
Last updated
22 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing KSI-301 and Aflibercept in people with Diabetic Macular Edema, run by Kodiak Sciences Inc at 75 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United States, Spain, Slovakia, Germany, Latvia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in BCVA (time frame: Day 1 to Week 64). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04611152.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.

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