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)

NCT04592419 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: KS301P1032020-001061-37
• Study Type: interventional
• Target: 568
• Locations: 12 countries
• Sites: 141

Brief 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).

Conditions

Macular Edema; Retinal Vein Occlusion

Keywords

RVO; Kodiak; KSI-301; Vascular endothelial growth factor; Anti-VEGF; VEGF; Antibody biopolymer conjugate; Retinal Degeneration; Retinal Diseases; Eye Diseases; Vision Disorders; Vision, low; Aflibercept; Eylea

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (8)

• Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.

  Day 1 - Week 48

• Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.

  Day 1 - Week 48

• Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants

  Day 1 - Week 48

• Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants.

  Day 1 - Week 48.

• Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants.

  Baseline - Week 48

Study Arms (2)

KSI-301 (Arm A)

EXPERIMENTAL

Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.

Drug: KSI-301; Other: Sham Procedure

Aflibercept (Arm B)

ACTIVE COMPARATOR

Intravitreal injection of aflibercept (2 mg) once every 4 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.

Drug: Aflibercept; Other: Sham Procedure

Interventions

KSI-301 DRUG

Intravitreal Injection

KSI-301 (Arm A)

Aflibercept DRUG

Intravitreal Injection

Also known as: Eylea

Aflibercept (Arm B)

Sham Procedure OTHER

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.

Aflibercept (Arm B); KSI-301 (Arm A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to participation in the study.
• 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.
• BCVA ETDRS letter score between 80 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 ME secondary to RVO.

You may not qualify if:

• Macular edema in the Study Eye for reasons other than RVO
• Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.
• Uncontrolled glaucoma in the Study Eye.
• Active retinal disease other than the condition under investigation in the Study Eye.
• 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
• Active or suspected ocular or periocular infection or inflammation
• 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).
• 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.

Sponsors & Collaborators

• Kodiak Sciences Inc: lead

Study Sites (141)

Northwest Arkansas Retina Associates

Phoenix, Arizona, 85014, United States

Location

Retinal Research Institute, LLC

Phoenix, Arizona, 85014, United States

Location

Retina Vitreous Associates

Beverly Hills, California, 90211, United States

Location

Eye Medical Center of Fresno

Fresno, California, 93720, United States

Location

Retina Consultants of Orange County

Fullerton, California, 92835, United States

Location

UCSD Jacobs Retina Center

La Jolla, California, 92037, United States

Location

Northern California Retina Vitreous Associates

Mountain View, California, 94040, United States

Location

Retina Consultants of San Diego

Poway, California, 92064, United States

Location

Retina Consultants of Southern California

Redlands, California, 92374, United States

Location

Retinal Consultants Medical Group Inc

Sacramento, California, 95819, United States

Location

Orange County Retina Medical Group

Santa Ana, California, 92705, United States

Location

California Retina Consultants

Santa Maria, California, 93454, United States

Location

Colorado Retina Associates PC

Lakewood, Colorado, 80228, United States

Location

Conneticut Eye Consultants

Danbury, Connecticut, 06810, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385, United States

Location

Florida Eye Clinic

Altamonte Springs, Florida, 32701, United States

Location

Retina Group of Florida

Boca Raton, Florida, 33431, United States

Location

Florida Eye Microsurgical Institute

Boynton Beach, Florida, 33426, United States

Location

The Macula Center/ Blue Ocean Clinical Research

Clearwater, Florida, 33761, United States

Location

Rand Eye Institute

Deerfield Beach, Florida, 33064, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Vitreo Retinal Associates

Gainesville, Florida, 32607, United States

Location

Florida Eye Associates

Melbourne, Florida, 32901, United States

Location

Florida Retina Institute

Orlando, Florida, 32806, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Southern Vitreoretinal Associates

Tallahassee, Florida, 32308, United States

Location

Retina Associates of Florida

Tampa, Florida, 33609, United States

Location

Center for Retina & Macular Disease

Winter Haven, Florida, 33880, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

Springfield Clinic LLP

Springfield, Illinois, 62703, United States

Location

Talley Eye

Evansville, Indiana, 47710, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Retina Associates PA

Lenexa, Kansas, 66215, United States

Location

Vitreo Retinal Consultants and Surgeons

Wichita, Kansas, 67214, United States

Location

Retina Associates of Kentucky

Lexington, Kentucky, 40509, United States

Location

Maine Eye Center

Portland, Maine, 04102, United States

Location

Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Cumberland Valley Retina Consultants PC

Hagerstown, Maryland, 21740, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Vitreo Retinal Associates PC

Worcester, Massachusetts, 01603, United States

Location

Foundation for Vision Research

Grand Rapids, Michigan, 49525, United States

Location

Associated Retinal Consultants PC

Royal Oak, Michigan, 78073, United States

Location

Vitreoretinal Surgery PA

Edina, Minnesota, 55435, United States

Location

Retina Consultants of NV

Henderson, Nevada, 89052, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

The Retina Center of New Jersey

Bloomfield, New Jersey, 07017, United States

Location

NJ Retina

Teaneck, New Jersey, 07605, United States

Location

Vitreo Retinal Consultants

Hauppauge, New York, 11788, United States

Location

Retina-Vitreous Surgeons of Central NY

Liverpool, New York, 13088, United States

Location

Ocli Vision

Oceanside, New York, 11572, United States

Location

Retina Associates of Western NY

Rochester, New York, 14620, United States

Location

Asheville Eye Associates

Asheville, North Carolina, 28803, United States

Location

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

Charlotte, North Carolina, 28210, United States

Location

Retina Associates of Cleveland

Beachwood, Ohio, 44122, United States

Location

Retina Associates of Cleveland

Cleveland, Ohio, 44130, United States

Location

Retina Northwest

Portland, Oregon, 97210, United States

Location

Retina Consultants, LLC

Salem, Oregon, 97302, United States

Location

Cascade Medical Research Institute

Springfield, Oregon, 97477, United States

Location

Retina Research of Beaufort

Beaufort, South Carolina, 29902, United States

Location

Retina Consultants of Carolina

Greenville, South Carolina, 29605, United States

Location

Charleston Neuroscience Institute

Ladson, South Carolina, 29456, United States

Location

Pametto Retina Center

West Columbia, South Carolina, 29501, United States

Location

Black Hills Regional Eye Institute

Rapid City, South Dakota, 57701, United States

Location

Charles Retina Institute

Germantown, Tennessee, 38138, United States

Location

Southeastern Retina Associates PC

Knoxville, Tennessee, 37909, United States

Location

Tennessee Retina PC

Nashville, Tennessee, 37203, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Austin Research Center for Retina

Austin, Texas, 78705, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Retina Research Center

Austin, Texas, 78705, United States

Location

Retina Consultants of Texas

Houston, Texas, 77030, United States

Location

Retina Consultants of Texas - (Katy)

Katy, Texas, 77494, United States

Location

Texas Retina Associates

Plano, Texas, 75075, United States

Location

Austin Retina Associates (Round Rock)

Round Rock, Texas, 78681, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retina Consultants of Texas - (Woodlands)

The Woodlands, Texas, 77384, United States

Location

Strategic Clinical Research Group, LLC

Willow Park, Texas, 76087, United States

Location

Retina Institute of Virginia

Richmond, Virginia, 23235, United States

Location

Retina Center Northwest

Silverdale, Washington, 98383, United States

Location

Spokane Eye

Spokane, Washington, 99204, United States

Location

OFTEX s.r.o.

Pardubice, 53002, Czechia

Location

Vseobecna Fakultni

Prague, 128 08, Czechia

Location

Lekarna BENU

Prague, 150 00, Czechia

Location

CHRU Dijon Complexe Du Bocage

Dijon, Côte-d'Or, 21079, France

Location

Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin

Bordeaux, Gironde, 33076, France

Location

Hôpital de La Croix Rousse

Lyon, Rhône, 69317, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France

Location

Centre Paradis Monticelli

Marseille, 13008, France

Location

Hôpital Lariboisière - Service Pharmacie

Paris, 75 010, France

Location

Fondation Rothschild

Paris, 75019, France

Location

CHRU de Poitiers La Miletrie

Poitiers, 86021, France

Location

Universitätsklinikum Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Dietrich Bonhoeffer Klinikum Neubrandenburg

Neubrandenburg, Mecklenburg-Vorpommern, 17036, Germany

Location

St. Elisabeth Krankenhaus

Cologne, North Rhine-Westphalia, 50935, Germany

Location

Miriam Kannenbaeumer or Andrea Koschinski

Münster, North Rhine-Westphalia, 48145, Germany

Location

MH EK Honvedkorhaz SzemEszeti Osztaly

Budapest, 1062, Hungary

Location

Semmelweis Egyetem

Budapest, 1085, Hungary

Location

Bajcsy-Zsilinszky Korhaz es Rendelointezet

Budapest, 1106, Hungary

Location

Budapest Retina Associates Kft

Budapest, 1133, Hungary

Location

Jahn Ferenc Dél-Pesti Kórház és Rendelointézet

Budapest, 1214, Hungary

Location

Bnai Zion

Haifa, 31048, Israel

Location

Rambam MC

Haifa, 31096, Israel

Location

Hadassah University Hospital

Jerusalem, 91120, Israel

Location

Meir MC

Kfar Saba, 44281, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Kaplan MC

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Assuta HaShalom

Tel Aviv, 6789140, Israel

Location

Shamir Medical Center Assaf Harofeh

Tzrifin, 70300, Israel

Location

Ospedale Clinicizzato SS Annunziata

Chieti, Abruzzo, 66100, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Rome, Lazio, 00133, Italy

Location

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, 00168, Italy

Location

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy, 20132, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia

Udine, 33100, Italy

Location

Signes Ozolinas Doctor Praxis In Ophthalmology

Jelgava, LV-3001, Latvia

Location

Pauls Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Location

Riga Eastern Clinical University Hospital Clinic Bikernieki

Riga, LV-1006, Latvia

Location

Latvian American Eye Center

Riga, LV-1009, Latvia

Location

Optimum Profesorskie Centrum Okulistyki

Gdansk, Pomeranian Voivodeship, 80-809, Poland

Location

Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi

Katowice, Silesian Voivodeship, 40-514, Poland

Location

Gabinet Okulistyczny Prof. Edward Wylegala

Katowice, Silesian Voivodeship, 40-594, Poland

Location

Oftalmika Sp. z o.o.

Bydgoszcz, 85-631, Poland

Location

Dr Nowosielska Okulistyka i Chirurgia Oka

Warsaw, 01-249, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

Emanuelli Research & Development Center LLC

Arecibo, 00612, Puerto Rico

Location

Fakultna nemocnica s poliklinikou F. D. Roosevelta

Banská Bystrica, 974 01, Slovakia

Location

Univerzitna nemocnica Bratislava

Bratislava, 826 06, Slovakia

Location

Uvea Klinika, S.R.O.

Martin, 036 01, Slovakia

Location

Nemocnica s poliklinikou Trebisov a.s.

Trebišov, 075 01, Slovakia

Location

Fakultna nemocnica Trencin

Trencín, 911 01, Slovakia

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitari General de Catalunya - Grupo Quironsalud

Sant Cugat del Vallès, Barcelona, 08195, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital dos de Maig

Barcelona, 08025, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08028, Spain

Location

Instituto Clinico Quirurgico de Oftalmologia

Bilbao, 48010, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Universitario Rio Hortega

Valladolid, 47012, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Macular Edema; Retinal Vein Occlusion; Retinal Degeneration; Retinal Diseases; Eye Diseases; Vision Disorders; Vision, Low

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Macular Degeneration; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Eye Diseases, Hereditary; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Pablo Velazquez-Martin, MD
• Organization: Kodiak Sciences Inc.

ClinOps@kodiak.com

1 (650) 281-0850

Study Officials

• Pablo Velazquez-Martin, MD

  Kodiak Sciences Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: For masking purposes, sham injections will be administered at every monthly visit if an active treatment is not administered. To preserve masking, two investigators are required for this study. The masked Investigator will be responsible for the examinations and safety assessments. The unmasked Investigator will perform the injections and post-treatment assessments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 1:1 into one of two treatment arms: KSI-301 or aflibercept. Participants in the Extension Phase will be treated with KSI-301.

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 19, 2020
• Study Start: September 25, 2020
• Primary Completion: June 10, 2022
• Study Completion: January 19, 2023
• Last Updated: June 26, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8); IL (9); US (81); IT (5); LA (4); HU (5); PL (6); PR (1); ES (10); DE (4); CZ (3); SL (5)