Study to Assess the Efficacy & Safety of KHK4951 in Patients With Diabetic Macular Edema

October 29, 2025 updated by: Kyowa Kirin Co., Ltd.

A Phase 2, Multicenter, Randomized, Double-Masked, Parallel-Group Study to Assess the Efficacy and Safety of KHK4951, a Vascular Endothelial Growth Factor Receptor Inhibitor, in Patients With Diabetic Macular Edema

The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with DME.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Albury, New South Wales, Australia, 02640
        • Eye Clinic Albury Wodonga
      • Liverpool, New South Wales, Australia, 2170
        • South West Retina
      • Parramatta, New South Wales, Australia, 02150
        • Marsden Eye Specialists
      • Strathfield, New South Wales, Australia, 2135
        • Strathfield Retina Clinic
      • Sydney, New South Wales, Australia, 2000
        • Sydney Eye Hospital
      • Sydney, New South Wales, Australia, 2000
        • Sydney Retina Clinic & Day Surgery
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Adelaide Eye and Retina Centre
    • Tasmania
      • Hobart, Tasmania, Australia, 7008
        • Hobart Eye Surgeons
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Centre For Eye Research Australia
  • Japan
      • Fukuoka, Japan, 812-0011
        • Hayashi Eye Hospital - Ophthalmology
      • Fukushima, Japan, 960-1295
        • Fukushima Medical University Hospital - Ophthalmology
      • Kyoto, Japan, 607-8062
        • Rakuwakai Otowa Hospital
      • Saitama, Japan, 330-8553
        • Saitama Red Cross Hospital
    • Aichi-ken
      • Nagakute, Aichi-ken, Japan, 480-1195
        • Aichi Medical University Hospital - Ophthalmology
      • Nagoya, Aichi-ken, Japan, 462-0825
        • MIYAKE Eye Hospital
    • Chiba
      • Sakura, Chiba, Japan, 285-8741
        • Toho University Medical Center Sakura Hospital
    • Fukuoka
      • Kurume, Fukuoka, Japan, 830-0011
        • Kurume University Hospital
    • Fukushima
      • Kōriyama, Fukushima, Japan, 963-8563
        • Minamitohoku Eye Clinic
    • Hokkaidô
      • Sapporo, Hokkaidô, Japan, 060-0031
        • Caress Sapporo Tokeidai Memorial Hospital
    • Hyôgo
      • Kobe, Hyôgo, Japan, 650-0017
        • Kobe University Hospital - Ophthalmology
    • Ibaraki
      • Mito, Ibaraki, Japan, 310-0845
        • Kozawa eye hospital and diabetes center
    • Kagawa-ken
      • Kita-gun, Kagawa-ken, Japan, 761-0793
        • Kagawa University Hospital
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Shinshu University Hospital - Ophthalmology
    • Nara
      • Kashihara, Nara, Japan, 634-8522
        • Nara Medical University Hospital - Ophthalmology
    • Osaka
      • Hirakata, Osaka, Japan, 660-0892
        • Kansai Medical University Medical Center
      • Sayama, Osaka, Japan, 577-8502
        • Kindai University Hospital
    • Shizuoka
      • Susono, Shizuoka, Japan, 410-1102
        • Muramatsu Clinic Muramatsu Eye Clinic - Ophthalmology
    • Tochigi
      • Shimotsuke, Tochigi, Japan, 329-0498
        • Jichi Medical University Hospital
    • Tokyo
      • Chiyoda City, Tokyo, Japan
        • Nihon University Hospital
      • Hachiōji, Tokyo, Japan, 193-0998
        • Tokyo Medical University Hachioji Medical Center
      • Meguro City, Tokyo, Japan, 152-8902
        • Tokyo Medical Center
      • Shinjuku, Tokyo, Japan, 160-8582
        • Keio University Hospital - Ophthalmology
    • Ôsaka
      • Osaka, Ôsaka, Japan, 545-0051
        • Osaka Metropolitan university Hospital
  • South Korea
      • Seoul, South Korea, 6591
        • The Catholic Univ of KOR, SSMH
    • Dalseo-gu
      • Daegu, Dalseo-gu, South Korea, 42601
        • Keimyung University Dongsan Hospital
    • Gudeok-ro
      • Busan, Gudeok-ro, South Korea, 49241
        • Pusan National University Hospital
    • Gyeonggido
      • Seongam, Gyeonggido, South Korea, 13620
        • Seoul National University Bundang Hospital
      • Seongnam-si, Gyeonggido, South Korea, 13496
        • CHA Bundang Medical Center, CHA University
    • Nam-gu
      • Daegu, Nam-gu, South Korea, 42415
        • Yeungnam University Hospital
    • Namdong-gu
      • Incheon, Namdong-gu, South Korea, 21565
        • Gachon University Gil Medical Center
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, South Korea, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Seoul Teugbyeolsi, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, Seoul Teugbyeolsi, South Korea, 05505
        • Asan Medical Center
      • Seoul, Seoul Teugbyeolsi, South Korea, 06351
        • Samsung Medical Center
      • Seoul, Seoul Teugbyeolsi, South Korea, 02841
        • Korea University Anam Hospital
      • Seoul, Seoul Teugbyeolsi, South Korea, 07301
        • Kim Eye Hospital
      • Seoul, Seoul Teugbyeolsi, South Korea, 2447
        • Kyung Hee University Hospital
  • United States
    • Arizona
      • Mesa, Arizona, United States, 85206
        • Barnet Dulaney Perkins Eye Center - Phoenix
      • Tucson, Arizona, United States, 85710
        • Retina Associates Southwest, P.C.
    • California
      • Arcadia, California, United States, 91006
        • Win Retina
      • Beverly Hills, California, United States, 90211
        • Retina Vitreous Associates Medical Group
      • Encino, California, United States, 91436
        • The Retina Partners
      • Huntington Beach, California, United States, 92647
        • Salehi Retina Institute, Inc
      • Pasadena, California, United States, 91107
        • California Eye Specialists Medical Group Inc
      • Redlands, California, United States, 92374
        • Retina Consultants of Southern California
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Retina Consultants of Southern CO
    • Florida
      • Clearwater, Florida, United States, 33761
        • Blue Ocean Clinical Research West
      • Melbourne, Florida, United States, 32901
        • Florida Eye Associates
      • Pinellas Park, Florida, United States, 33782
        • Eye Associates of Pinellas
      • Plantation, Florida, United States, 33324
        • Ft. Lauderdale Eye Institute
      • St. Petersburg, Florida, United States, 33711
        • Retina Vitreous Associates of Florida - Saint Petersburg
      • Tallahassee, Florida, United States, 32308
        • Southern Vitreoretinal Associates
      • Winter Haven, Florida, United States, 33880
        • Center for Retina and Macular Disease - Ophthalmology
    • Maryland
      • Hagerstown, Maryland, United States, 21740
        • Mid Atlantic Retina Specialists - Hagerstown
    • Nevada
      • Reno, Nevada, United States, 89502
        • Sierra Eye Associates
    • New Jersey
      • Bloomfield, New Jersey, United States, 07003
        • Envision Ocular, LLC
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Vision Research Center Eye Associates of New Mexico
    • New York
      • Liverpool, New York, United States, 13088
        • Retina Vitreous Surgeons of Central NY, PC
      • Oceanside, New York, United States, 11572
        • Ophthalmic Consultants of Long Island
    • Oklahoma
      • Edmond, Oklahoma, United States, 73013
        • Retina Vitreous Center in Edmond Oklahoma
    • Oregon
      • Portland, Oregon, United States, 97225
        • EyeHealth Northwest
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Wills Eye Health System
      • Kingston, Pennsylvania, United States, 18704
        • Eye Care Specialists
    • South Carolina
      • Charleston, South Carolina, United States, 29414
        • Retina Consultants of Charleston - (RCA Network Site)
      • Ladson, South Carolina, United States, 29456
        • Charleston Neuroscience Institute (RCA Network Site)
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Black Hills Regional Eye Institute - Ophthalmology
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Charles Retina Institute
    • Texas
      • Abilene, Texas, United States, 79606
        • Retina Research Institute of Texas
      • Austin, Texas, United States, 78750
        • Austin Clinical Research, LLC
      • Austin, Texas, United States, 78705
        • Austin Retina Associates - Ophthalmology/Retina (RCA Network site)
      • Bellaire, Texas, United States, 77401
        • Retina Consultants of Texas
      • Fort Worth, Texas, United States, 76104
        • Texas Retina Associates
      • San Antonio, Texas, United States, 78240
        • Retinal Consultants of Texas- San Antonio (RCA Network site)
      • The Woodlands, Texas, United States, 77384
        • Retina Consultants of Texas (RCA Network Site)
      • Willow Park, Texas, United States, 76087
        • Strategic Clinical Research Group, LLC
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Fletcher Allen Health Care
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Retina Group of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Voluntary written informed consent to participate in the study
  • In Korea, participants must be 19 years or older to be enrolled
  • BCVA ETDRS letter score of 78 letters to 35 letters as measured by the ETDRS visual acuity chart in the study eye at screening
  • 500 μm ≥ CST ≥ 325 μm in the study eye at screening
  • HbA1c ≤ 11% at screening

Exclusion Criteria:

  • Any signs of proliferative diabetic retinopathy in the study eye
  • History of rubeosis in the study eye
  • Uncontrolled glaucoma in the study eye
  • Aphakia or pseudophakia with AC-IOL in the study eye
  • Active intraocular inflammation in the study eye
  • Any current ocular condition for which visual acuity loss would not improve from resolution of macular edema in the study eye
  • History of rhegmatogenous retinal detachment in the study eye
  • Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye

  • History of the following therapies in the study eye

    • History of vitrectomy surgery, submacular surgery, or other surgical intervention for DME
    • Periocular or intraocular (sub-Tenon or IVT) corticosteroids within 12 weeks prior to Day 1 corticosteroids
    • Previous intraocular device implantation except PC-IOL
    • Laser (any type) to the macular area within 12 weeks prior to Day 1
    • Peripheral retinal photocoagulation therapy within 12 weeks prior to Day 1
    • Previous treatment with IVT anti-VEGF drugs other than ranibizumab, bevacizumab, aflibercept 2 mg, and their biosimilars
    • Treatment with ranibizumab, bevacizumab, aflibercept 2 mg, or their biosimilars within 12 weeks prior to Day 1. Previously treated patients who received these medications more than 12 weeks prior to Day 1 can be enrolled, but the patients should be diagnosed with DME within 3 years prior to Day 1
    • Previous use of Ozurdex® or Iluvien® implant
  • Any current or history of endophthalmitis in either eye
  • History of idiopathic or autoimmune-associated uveitis in either eye
  • Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
KHK4951 High dose
Drug: KHK4951
KHK4951 eye drop for 36 weeks until end of the trial
Drug: Aflibercept Injection
Intravitreal injection (IVT) of aflibercept will be given as specified in the protocol
Experimental: Arm B
KHK4951 Middle dose
Drug: KHK4951
KHK4951 eye drop for 36 weeks until end of the trial
Drug: Aflibercept Injection
Intravitreal injection (IVT) of aflibercept will be given as specified in the protocol
Experimental: Arm C
KHK4951 Low dose
Drug: KHK4951
KHK4951 eye drop for 36 weeks until end of the trial
Drug: Aflibercept Injection
Intravitreal injection (IVT) of aflibercept will be given as specified in the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction of 15 or more letters in BCVA (Best corrected visual acuity) as measured by ETDRS visual acuity chart from baseline
Time Frame: For 36 weeks until the end of the trial
For 36 weeks until the end of the trial

Secondary Outcome Measures

Outcome Measure
Time Frame
The number of aflibercept IVT
Time Frame: For 36 weeks until the end of the trial
For 36 weeks until the end of the trial
Change from baseline in SHRM as measured by SD-OCT
Time Frame: 36 Weeks
36 Weeks
Change from baseline in retinal morphology as measured by SD-OCT
Time Frame: 36 Weeks
36 Weeks
Change from baseline in leakage as measured by FA
Time Frame: 36 Weeks
36 Weeks

Other Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse events
Time Frame: For 36 weeks until the end of the trial
For 36 weeks until the end of the trial
Serum KHK4951 concentration
Time Frame: 36 Weeks
36 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kyowa Kirin Co., Ltd.

Investigators

  • Study Director: Sotaro Takigawa, Kyowa Kirin Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 9, 2024

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

October 31, 2023

First Submitted That Met QC Criteria

October 31, 2023

First Posted (Actual)

November 3, 2023

Study Record Updates

Last Update Posted (Estimated)

October 30, 2025

Last Update Submitted That Met QC Criteria

October 29, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4951-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin will be available in the Vivli repository, https://vivli.org/ourmember/kyowakirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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