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

NCT04603937 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: KS301P1052020-001063-82
• Study Type: interventional
• Target: 459
• Locations: 8 countries
• Sites: 72

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 KS301P105

  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 (72)

Retinal Research Institute, LLC

Phoenix, Arizona, 85014, United States

Location

Retina Vitreous Associates

Beverly Hills, California, 90211, United States

Location

Retina Consultants of Orange County

Fullerton, California, 92835, 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

Retinal Consultants Medical Group Inc

Sacramento, California, 95825, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385, United States

Location

Florida Eye Microsurgical Institute

Boynton Beach, Florida, 33426, United States

Location

Rand Eye Institute

Deerfield Beach, Florida, 33064, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Retina Vitreous Associates of Florida

St. Petersburg, Florida, 33703, United States

Location

Southern Vitreoretinal Associates

Tallahassee, Florida, 32308, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

Georgia Retina, P.C.

Marietta, Georgia, 30060, United States

Location

Retina Consultants of Hawaii, Inc

‘Aiea, Hawaii, 96701, United States

Location

Retina Specialists of Idaho

Boise, Idaho, 83713, United States

Location

Talley Eye

Evansville, Indiana, 47710, United States

Location

Maine Eye Center

Portland, Maine, 04101, United States

Location

Associated Retinal Consultants PC

Royal Oak, Michigan, 48073, United States

Location

Vitreoretinal Surgery PA

Minneapolis, Minnesota, 55435, United States

Location

Retina Consultants of NV

Henderson, Nevada, 89052, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, 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

Ophthalmic Consultants of Long Island

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

Cleveland Clinic Foundation, Cole Eye Institute

Cleveland, Ohio, 44195, United States

Location

Retina Consultants, LLC

Salem, Oregon, 97302, United States

Location

Southeastern Retina Associates PC

Knoxville, Tennessee, 37922, 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

Texas Retina Associates

Fort Worth, Texas, 76108, United States

Location

Retina Consultants of Houston-(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 Houston - (Woodlands)

The Woodlands, Texas, 77384, United States

Location

Retina Institute of Virginia

Richmond, Virginia, 23235, 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

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 , Essais cliniques - Aude Jacob

Paris, 75 010, France

Location

Fondation Rothschild

Paris, 75019, France

Location

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz , Josa Andras Oktatókórház

Nyíregyháza, Szabolcs-Szatmár-Bereg, H-4400, 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

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

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, 00168, Italy

Location

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy, 20132, Italy

Location

AOU dell'Università degli Studi della Campania Luigi Vanvitelli

Naples, 80131, Italy

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

Oftalmika Sp. z o.o.

Bydgoszcz, 85-631, Poland

Location

Dr Nowosielska Okulistyka i Chirurgia Oka

Warsaw, 01-249, Poland

Location

Specjalistyczny Szpital im. Alfreda Sokolowskiego

Wałbrzych, 58-309, 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

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

1 (650) 281-0850

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 21, 2020
• First Posted: October 27, 2020
• Study Start: September 30, 2020
• Primary Completion: April 27, 2023
• Study Completion: August 31, 2023
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6); PR (1); IL (9); HU (4); IT (3); PL (6); CZ (3); US (40)