A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO)

Macular Edema Clinical Trial

— BEACON  

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 Due to Treatment-naïve Macular Edema Secondary to Retinal Vein Occlusion (RVO)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04592419
• Other study ID #: KS301P103
• Secondary ID: 2020-001061-37
• Status: Completed
• Phase: Phase 3
• Start date: September 25, 2020
• Est. completion date: January 19, 2023

Study information

• Verified date: May 2024
• 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 macular edema due to treatment-naïve branch (BRVO) or central retinal vein occlusion (CRVO).

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 visual impairment due to treatment-naïve macular edema secondary to RVO (either branch or central type).

The primary endpoint will be assessed at Week 24; additional secondary endpoints for efficacy will be assessed at Week 24 and Week 48.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 568
• Est. completion date: January 19, 2023
• Est. primary completion date: June 10, 2022
• 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 macular edema of 6 months duration or less due to CRVO or BRVO. Participants with hemiretinal vein occlusion will be included as CRVO.

3. BCVA ETDRS letter score between 80 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 ME secondary to RVO.

6. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

1. Macular edema in the Study Eye for reasons other than RVO

2. Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.

3. Uncontrolled glaucoma in the Study Eye.

4. Active retinal disease other than the condition under investigation in the Study Eye.

5. Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention alter visual acuity during the study

6. Active or suspected ocular or periocular infection or inflammation

7. Any prior use of an approved or investigational treatment for macular edema secondary to RVO in the Study Eye (e.g. anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).

8. Women who are pregnant or lactating or intending to become pregnant during the study.

9. Uncontrolled blood pressure defined as a systolic value = 180 mmHg or diastolic value =100 mmHg while at rest

10. 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.

11. 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.

12. Other protocol-specified exclusion criteria may apply.

Related Conditions & MeSH terms

• Edema
• Macular Edema
• Retinal Vein Occlusion

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 Universitaire de Bordeaux, Hopital Pellegrin	Bordeaux	Gironde
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	Paris
France	CHRU de Poitiers La Miletrie	Poitiers
Germany	St. Elisabeth Krankenhaus	Köln	Nordrhein-Westfalen
Germany	Miriam Kannenbaeumer or Andrea Koschinski	Münster	Nordrhein-Westfalen
Germany	Dietrich Bonhoeffer Klinikum Neubrandenburg	Neubrandenburg	Mecklenburg-Vorpommern
Germany	Universitätsklinikum Regensburg	Regensburg	Bayern
Hungary	Bajcsy-Zsilinszky Korhaz es Rendelointezet	Budapest
Hungary	Budapest Retina Associates Kft	Budapest
Hungary	Jahn Ferenc Dél-Pesti Kórház és Rendelointézet	Budapest
Hungary	MH EK Honvedkorhaz SzemEszeti Osztaly	Budapest
Hungary	Semmelweis Egyetem	Budapest
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 Clinicizzato SS Annunziata	Chieti	Abruzzo
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Italy	Fondazione PTV Policlinico Tor Vergata	Roma	Lazio
Italy	Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia	Udine
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
Poland	Oftalmika Sp. z o.o.	Bydgoszcz
Poland	Optimum Profesorskie Centrum Okulistyki	Gdansk	Pomorskie
Poland	Gabinet Okulistyczny Prof. Edward Wylegala	Katowice	Slaskie
Poland	Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi	Katowice	Slaskie
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
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.	Trebišov
Slovakia	Fakultna nemocnica Trencin	Trencín
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital dos de Maig	Barcelona
Spain	Instituto Clinico Quirurgico de Oftalmologia	Bilbao
Spain	Hospital Universitario de Bellvitge	L'hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitari General de Catalunya - Grupo Quironsalud	Sant Cugat Del Vallès	Barcelona
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	Retina Research Institute of Texas	Abilene	Texas
United States	Florida Eye Clinic	Altamonte Springs	Florida
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	Austin Retina Associates	Austin	Texas
United States	Retina Research Center	Austin	Texas
United States	Retina Associates of Cleveland	Beachwood	Ohio
United States	Retina Research of Beaufort	Beaufort	South Carolina
United States	Retina Vitreous Associates	Beverly Hills	California
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	Florida Eye Microsurgical Institute	Boynton Beach	Florida
United States	Charlotte Eye Ear Nose & Throat Associates, P.A.	Charlotte	North Carolina
United States	Retina Group of Washington	Chevy Chase	Maryland
United States	The Macula Center/ Blue Ocean Clinical Research	Clearwater	Florida
United States	Retina Associates of Cleveland	Cleveland	Ohio
United States	Conneticut Eye Consultants	Danbury	Connecticut
United States	Rand Eye Institute	Deerfield Beach	Florida
United States	Vitreoretinal Surgery PA	Edina	Minnesota
United States	Talley Eye	Evansville	Indiana
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Eye Medical Center of Fresno	Fresno	California
United States	Retina Consultants of Orange County	Fullerton	California
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	Retina Consultants of Carolina	Greenville	South Carolina
United States	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland
United States	Vitreo Retinal Consultants	Hauppauge	New York
United States	Retina Consultants of NV	Henderson	Nevada
United States	Retina Consultants of Texas	Houston	Texas
United States	Retina Consultants of Texas - (Katy)	Katy	Texas
United States	Southeastern Retina Associates PC	Knoxville	Tennessee
United States	UCSD Jacobs Retina Center	La Jolla	California
United States	Charleston Neuroscience Institute	Ladson	South Carolina
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	Retina-Vitreous Surgeons of Central NY	Liverpool	New York
United States	Florida Eye Associates	Melbourne	Florida
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Tennessee Retina PC	Nashville	Tennessee
United States	Ocli Vision	Oceanside	New York
United States	Florida Retina Institute	Orlando	Florida
United States	Retina Specialty Institute	Pensacola	Florida
United States	Northwest Arkansas Retina Associates	Phoenix	Arizona
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 Northwest	Portland	Oregon
United States	Retina Consultants of San Diego	Poway	California
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Retina Consultants of Southern California	Redlands	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 Consultants, LLC	Salem	Oregon
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Orange County Retina Medical Group	Santa Ana	California
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	Southern Vitreoretinal Associates	Tallahassee	Florida
United States	Retina Associates of Florida	Tampa	Florida
United States	NJ Retina	Teaneck	New Jersey
United States	Retina Consultants of Texas - (Woodlands)	The Woodlands	Texas
United States	Retina Group of New England	Waterford	Connecticut
United States	Pametto 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
United States	Vitreo Retinal Associates PC	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Kodiak Sciences Inc

Countries where clinical trial is conducted

United States,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Latvia,  Poland,  Puerto Rico,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 to Week 24
Primary	Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 to Week 24
Secondary	Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.	Day 1 - Week 48
Secondary	Percentage of Participants Who Gain = 5, =10 and =15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.	Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100*n/N.	Day 1 - Week 48
Secondary	Percentage of Participants Who Lose = 5, =10 and =15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants	Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100*n/N.	Day 1 - Week 48
Secondary	Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (=69 ETDRS Letters) for All RVO Participants.	Percentage of participants with BCVA Snellen Equivalent of 20/40 or Better from Baseline to Week 48. Snellen Equivalent of 20/40 is 69 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100*n/N.	Day 1 - Week 48.
Secondary	Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (= 38 ETDRS Letters) Over Time for All RVO Participants.	Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse from Baseline to Week 48. Snellen Equivalent of 20/200 is 38 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100*n/N.	Baseline - Week 48
Secondary	Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants.	Macular Edema (ME) is assessed by optical coherence tomography (OCT) central subfield thickness (CST). A thickness of less than 325 microns is considered absence of ME. Proportion of participants with Absence of Macular Edema from Baseline to Week 48. Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100*n/N.	Baseline - Week 48
Secondary	Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants.	Mean change in OCT central subfield retinal thickness (CST) from baseline by visit over time (up to Week 48) for all RVO participants.	Day 1 - Week 48
Secondary	Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants.	Mean change in OCT center point retinal thickness (CPT) from baseline by visit over time (up to Week 48) for all RVO participants.	Day 1 - Week 48