A Study 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

— GLIMMER  

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: NCT04603937
• Other study ID #: KS301P105
• Secondary ID: 2020-001063-82
• 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: 459
• Est. completion date: August 31, 2023
• Est. primary completion date: April 27, 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
Czechia	OFTEX s.r.o.	Pardubice
Czechia	Lekarna BENU	Praha
Czechia	Vseobecna Fakultni	Praha
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	CHRU Dijon Complexe Du Bocage	Dijon	Côte-d'Or
France	Hôpital de La Croix Rousse	Lyon	Rhône
France	Centre Paradis Monticelli	Marseille
France	Fondation Rothschild	Paris
France	Hôpital Lariboisière - Service Pharmacie , Essais cliniques - Aude Jacob	Paris
Hungary	Bajcsy-Zsilinszky Korhaz es Rendelointezet	Budapest
Hungary	Budapest Retina Associates Kft	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz , Josa Andras Oktatókórház	Nyíregyháza	Szabolcs-Szatmár-Bereg
Israel	Bnai Zion	Haifa
Israel	Rambam MC	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Meir MC	Kfar Saba
Israel	Rabin Medical Center	Petach Tikva
Israel	Kaplan MC	Rehovot
Israel	Assuta HaShalom	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Shamir Medical Center Assaf Harofeh	Tzrifin
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia
Italy	AOU dell'Università degli Studi della Campania Luigi Vanvitelli	Naples
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Poland	Oftalmika Sp. z o.o.	Bydgoszcz
Poland	Optimum Profesorskie Centrum Okulistyki	Gdansk	Pomorskie
Poland	Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi	Katowice	Slaskie
Poland	Specjalistyczny Szpital im. Alfreda Sokolowskiego	Walbrzych
Poland	Dr Nowosielska Okulistyka i Chirurgia Oka	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wroclaw
Puerto Rico	Emanuelli Research & Development Center LLC	Arecibo
United States	Retina Consultants of Hawaii, Inc	'Aiea	Hawaii
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Asheville Eye Associates	Asheville	North Carolina
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Research Center for Retina	Austin	Texas
United States	Retina Vitreous Associates	Beverly Hills	California
United States	Retina Specialists of Idaho	Boise	Idaho
United States	Florida Eye Microsurgical Institute	Boynton Beach	Florida
United States	Cleveland Clinic Foundation, Cole Eye Institute	Cleveland	Ohio
United States	Rand Eye Institute	Deerfield Beach	Florida
United States	Talley Eye	Evansville	Indiana
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Texas Retina Associates	Fort Worth	Texas
United States	Retina Consultants of Orange County	Fullerton	California
United States	Vitreo Retinal Consultants	Hauppauge	New York
United States	Retina Consultants of NV	Henderson	Nevada
United States	Retina Consultants of Houston-(Katy)	Katy	Texas
United States	Southeastern Retina Associates PC	Knoxville	Tennessee
United States	Retina-Vitreous Surgeons of Central NY	Liverpool	New York
United States	Georgia Retina, P.C.	Marietta	Georgia
United States	Vitreoretinal Surgery PA	Minneapolis	Minnesota
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Ophthalmic Consultants of Long Island	Oceanside	New York
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Texas Retina Associates	Plano	Texas
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Maine Eye Center	Portland	Maine
United States	Retina Consultants of San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Retina Associates of Western NY	Rochester	New York
United States	Austin Retina Associates (Round Rock)	Round Rock	Texas
United States	Associated Retinal Consultants PC	Royal Oak	Michigan
United States	Retinal Consultants Medical Group Inc	Sacramento	California
United States	Retina Vitreous Associates of Florida	Saint Petersburg	Florida
United States	Retina Consultants, LLC	Salem	Oregon
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Southern Vitreoretinal Associates	Tallahassee	Florida
United States	Retina Consultants of Houston - (Woodlands)	The Woodlands	Texas
United States	Retina Group of New England	Waterford	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Kodiak Sciences Inc

Countries where clinical trial is conducted

United States,  Czechia,  France,  Hungary,  Israel,  Italy,  Poland,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-inferiority of KSI-301 to Aflibercept measured by changes in BCVA.	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.	Improvement 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.	Improvement 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 DRSS.	Improvement if the 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