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

Diabetic Macular Edema Clinical Trial

— GLEAM  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04611152
• Other study ID #: KS301P104
• Secondary ID: 2020-001062-11
• Status: Terminated
• Phase: Phase 3
• Start date: September 30, 2020
• Est. completion date: August 31, 2023

Study information

• Verified date: September 2023
• Source: Kodiak Sciences Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 460
• Est. completion date: August 31, 2023
• Est. primary completion date: May 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• KSI-301
Intravitreal Injection
• Aflibercept
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.

Locations

Country	Name	City	State
Germany	Universitätsklinikum Freiburg	Freiburg	Baden-Württemberg
Germany	St. Elisabeth Krankenhaus	Köln	Nordrhein-Westfalen
Germany	St Franziskus Hospital	Münster	Nordrhein-Westfalen
Germany	Dietrich Bonhoeffer Klinikum Neubrandenburg	Neubrandenburg	Mecklenburg-Vorpommern
Germany	Universitätsklinikum Regensburg	Regensburg	Bayern
Hungary	Jahn Ferenc Dél-Pesti Kórház és Rendelointézet	Budapest
Hungary	Ganglion Medical Center	Pécs
Italy	Fondazione PTV Policlinico Tor Vergata	Roma
Latvia	Signes Ozolinas Doctor Praxis In Ophthalmology	Jelgava
Latvia	Latvian American Eye Center	Riga
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga Eastern Clinical University Hospital Clinic Bikernieki	Riga
Puerto Rico	Emanuelli Research & Development Center LLC	Arecibo
Slovakia	Fakultna nemocnica s poliklinikou Zilina	Žilina
Slovakia	Fakultna nemocnica s poliklinikou F. D. Roosevelta	Banská Bystrica
Slovakia	Univerzitna nemocnica Bratislava	Bratislava
Slovakia	Uvea Klinika, S.R.O.	Martin
Slovakia	Nemocnica s poliklinikou Trebisov a.s. Ocne oddelenie - jednonova zdravotna starostlivost	Trebišov
Slovakia	Fakultna nemocnica Trencin	Trencín
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital dos de Maig	Barcelona
Spain	Hospital Universitari General de Catalunya - Grupo Quironsalud	Barcelona
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Spain	Hospital Universitario Rio Hortega	Valladolid
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza
United States	Southwest Retina Specialists	Amarillo	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Austin Retina Associates	Austin	Texas
United States	Retina Research of Beaufort	Beaufort	South Carolina
United States	The Retina Center of New Jersey	Bloomfield	New Jersey
United States	Retina Group of Florida	Boca Raton	Florida
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Star Retina	Burleson	Texas
United States	Charleston Neuroscience Institute - West Ashley	Charleston	South Carolina
United States	Charlotte Eye Ear Nose & Throat Associates, P.A.	Charlotte	North Carolina
United States	Blue Ocean Clinical Research	Clearwater	Florida
United States	Conneticut Eye Consultants	Danbury	Connecticut
United States	Pametto Retina Center	Florence	South Carolina
United States	Vitreo Retinal Associates	Gainesville	Florida
United States	Charles Retina Institute	Germantown	Tennessee
United States	Foundation for Vision Research	Grand Rapids	Michigan
United States	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland
United States	Retina Consultants of Texas	Houston	Texas
United States	UCSD Jacobs Retina Center	La Jolla	California
United States	Charleston Neuroscience Institute	Ladson	South Carolina
United States	Florida Retina Consultants	Lakeland	Florida
United States	Colorado Retina Associates PC	Lakewood	Colorado
United States	Retina Associates PA	Lenexa	Kansas
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Piedmont Eye Center	Lynchburg	Virginia
United States	Florida Eye Associates	Melbourne	Florida
United States	Tennessee Retina PC	Nashville	Tennessee
United States	Florida Retina Institute	Orlando	Florida
United States	Retina Specialty Institute	Pensacola	Florida
United States	MidAtlantic Retina	Philadelphia	Pennsylvania
United States	Retina Northwest	Portland	Oregon
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Retina Consultants of Southern California	Redlands	California
United States	Retina Consultants of San Antonio	San Antonio	Texas
United States	California Retina Consultants	Santa Maria	California
United States	Retina Center Northwest	Silverdale	Washington
United States	Spokane Eye	Spokane	Washington
United States	Cascade Medical Research Institute	Springfield	Oregon
United States	Springfield Clinic LLP	Springfield	Illinois
United States	Retina Associates of Florida	Tampa	Florida
United States	Retina Vitreous Associates of Florida	Tampa	Florida
United States	NJ Retina	Teaneck	New Jersey
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Vitreo Retinal Consultants and Surgeons	Wichita	Kansas
United States	Strategic Clinical Research Group, LLC	Willow Park	Texas
United States	Center for Retina & Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kodiak Sciences Inc

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Italy,  Latvia,  Puerto Rico,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in BCVA to Assess Non-inferiority of KSI-301 to Aflibercept.	Demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best corrected visual acuity (BCVA).	Day 1 to Year 1
Secondary	Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in BCVA.	Change in best corrected visual acuity (BCVA).	Day 1 to Year 2
Secondary	Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in CST.	Change in central subfield thickness (CST).	Day 1 to Year 2
Secondary	Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in the diabetic retinopathy severity score (DRSS).	Change in diabetic retinopathy severity score (DRSS).	Day 1 to Year 2
Secondary	Durability of KSI-301 5 mg compared to aflibercept 2 mg measured by number of intravitreal injections during the study.	Mean number of intravitreal injections during the course of the study.	Day 1 to Year 2
Secondary	Safety and Tolerability of KSI-301 mg compared to aflibercept 2 mg measured by the number of ocular and systemic adverse events.	Incidence of ocular and systemic adverse events.	Day 1 to Year 2