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

NCT04611152 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: KS301P1042020-001062-11
• Study Type: interventional
• Target: 460
• Locations: 8 countries
• Sites: 75

Brief Summary

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

Conditions

Diabetic Macular Edema

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

Outcome Measures

Primary Outcomes (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.

  Day 1 to Week 64

Secondary Outcomes (5)

• Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined

  Day 1 to Week 52

• Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104

  Day 1 to Week 52

• Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval

  Week 56

• Mean Number of Intravitreal Injections

  Day 1 to Week 60

• Mean Change in OCT CST

  Day 1 to Week 64

Study Arms (2)

KSI-301 (Arm A)

EXPERIMENTAL

Intravitreal 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.

Drug: KSI-301; Other: Sham Procedure

Aflibercept (Arm B)

ACTIVE COMPARATOR

Intravitreal 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.

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 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%.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Kodiak Sciences Inc: lead

Study Sites (75)

UCSD Jacobs Retina Center

La Jolla, California, 92037, United States

Location

Retina Consultants of Southern California

Redlands, California, 92374, United States

Location

California Retina Consultants

Santa Maria, California, 93454, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, 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 Florida

Boca Raton, Florida, 33431, United States

Location

Blue Ocean Clinical Research

Clearwater, Florida, 33761, United States

Location

Vitreo Retinal Associates

Gainesville, Florida, 32607, United States

Location

Florida Retina Consultants

Lakeland, Florida, 33805, 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

Retina Associates of Florida

Tampa, Florida, 33609, United States

Location

Retina Vitreous Associates of Florida

Tampa, Florida, 33617, United States

Location

Center for Retina & Macular Disease

Winter Haven, Florida, 33880, United States

Location

Springfield Clinic LLP

Springfield, Illinois, 62703, 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

Cumberland Valley Retina Consultants PC

Hagerstown, Maryland, 21740, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Foundation for Vision Research

Grand Rapids, Michigan, 49525, 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

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

Charlotte, North Carolina, 28210, United States

Location

Retina Northwest

Portland, Oregon, 97210, United States

Location

Cascade Medical Research Institute

Springfield, Oregon, 97477, United States

Location

MidAtlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Retina Research of Beaufort

Beaufort, South Carolina, 29902, United States

Location

Charleston Neuroscience Institute - West Ashley

Charleston, South Carolina, 29414, United States

Location

Pametto Retina Center

Florence, South Carolina, 29501, United States

Location

Charleston Neuroscience Institute

Ladson, South Carolina, 29456, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169, 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

Tennessee Retina PC

Nashville, Tennessee, 37203, United States

Location

Southwest Retina Specialists

Amarillo, Texas, 79106, United States

Location

Texas Retina Associates

Arlington, Texas, 76012, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Star Retina

Burleson, Texas, 76028, United States

Location

Retina Consultants of Texas

Houston, Texas, 77030, United States

Location

Retina Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Strategic Clinical Research Group, LLC

Willow Park, Texas, 76087, United States

Location

Piedmont Eye Center

Lynchburg, Virginia, 24502, United States

Location

Retina Center Northwest

Silverdale, Washington, 98383, United States

Location

Spokane Eye

Spokane, Washington, 99204, United States

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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

St Franziskus Hospital

Münster, North Rhine-Westphalia, 48145, Germany

Location

Jahn Ferenc Dél-Pesti Kórház és Rendelointézet

Budapest, 1214, Hungary

Location

Ganglion Medical Center

Pécs, 7621, Hungary

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 00133, 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

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. Ocne oddelenie - jednonova zdravotna starostlivost

Trebišov, 075 01, Slovakia

Location

Fakultna nemocnica Trencin

Trencín, 911 01, Slovakia

Location

Fakultna nemocnica s poliklinikou Zilina

Žilina, 012 07, Slovakia

Location

Hospital dos de Maig

Barcelona, 08025, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08028, Spain

Location

Hospital Universitari General de Catalunya - Grupo Quironsalud

Barcelona, 08195, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28222, 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

Retinal Degeneration; Retinal Diseases; Eye Diseases; Vision Disorders; Vision, Low; Diabetes Mellitus; Diabetic Retinopathy; Macular Edema

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Macular Degeneration

Results Point of Contact

• Title: Pablo Velazquez-Martin
• Organization: Kodiak Sciences Inc

clinops@kodiak.com

6502810850

Study Officials

• Pablo Velazquez-Martin, MD

  Kodiak Sciences Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• 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.

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: November 2, 2020
• Study Start: September 30, 2020
• Primary Completion: May 11, 2023
• Study Completion: August 31, 2023
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-08

Locations

PR (1); US (48); ES (8); IT (1); SL (6); LA (4); HU (2); DE (5)