A Study of 2 Doses of EYE103 Compared With Ranibizumab (0.5 mg) in Participants With DME (BAROLO)

June 24, 2026 updated by: EyeBiotech Ltd.

A Randomized, Double-Masked, Multi-Center, 3-Arm Pivotal Phase 2/3 Study to Evaluate The Efficacy and Safety of Intravitreal EYE103 Compared With Intravitreal Ranibizumab (0.5mg) in Participants With Diabetic Macular Edema

EYE-RES-103 is a randomized, double masked pivotal study to evaluate the efficacy and safety of 2 dose levels of EYE103 in comparison with the active control, ranibizumab, in patients with diabetic macular edema (DME).

In the first year, all 3 treatment groups will be treated every 4 weeks with either EYE103 or ranibizumab. Beginning at Year 2, the frequency of treatment for participants will shift based on a personalized treatment interval algorithm.

Approximately 960 participants will be entered in the study.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

EYE-RES-103 is a randomized, double masked pivotal study to evaluate the efficacy and safety of 2 dose levels of EYE103 in comparison with the active control, ranibizumab, in patients with diabetic macular edema (DME).

Approximately 960 participants will be entered in the study. Participants will be randomized 1:1:1 to receive low dose EYE103, high dose EYE103, or 0.5 mg ranibizumab, administered via intravitreal injection. In the first year, all 3 treatment groups will be treated every 4 weeks with either EYE103 or ranibizumab. Beginning at Year 2, the frequency of treatment for participants will shift based on a personalized treatment interval (PTI) algorithm. Throughout the 2-year study, subjects will be evaluated every 4 weeks, including measurement of Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA), examination by slit-lamp biomicroscopy, fundoscopy, and spectral domain optical coherence tomography (SD-OCT). Among other parameters, SD-OCT will be used to measure central subfield thickness (CST) in microns.

Study Type

Interventional

Enrollment (Actual)

1054

Phase

  • Phase 2
  • Phase 3

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

  • Argentina
      • Buenos Aires, Argentina, 1015
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, 1023
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, 1120
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, B18321XE
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, B1878KDF
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, C1008
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, C1033AAW
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, C1116ABA
        • Buenos Aires, Argentina
      • Buenos Aires, Argentina, C1280AEB
        • Buenos Aires, Argentina
      • Córdoba, Argentina, X5000AAJ
        • Cordoba, Argentina
      • Córdoba, Argentina, X5000
        • Cordoba, Argentina
      • Salta, Argentina, 4400
        • Salta, Argentina
      • Salta, Argentina, A4400
        • Salta, Argentina
      • Santa Fe, Argentina, S2000
        • Santa Fe, Argentina
  • Brazil
      • Aparecida de Goiânia, Brazil, 74210-010
        • Aparecida de Goiania, Brazil
      • Aparecida de Goiânia, Brazil, 74980-010
        • Aparecida de Goiania, Brazil
      • Assis, Brazil, 19814-470
        • Assis, Brazil
      • Belo Horizonte, Brazil, 30330-000
        • Belo Horizonte, Brazil
      • Blumenau, Brazil, 89010-204
        • Blumenau, Brazil
      • Porto Alegre, Brazil, 90.440-051
        • Porto Alegre, Brazil
      • Sorocaba, Brazil, 18031-060
        • Sorocaba, Brazil
      • São Paulo, Brazil, 04023-062
        • Sao Paulo, Brazil
      • São Paulo, Brazil, 04038-032
        • Sao Paulo, Brazil
      • Vitória, Brazil, 29055-450
        • Vitoria, Brazil
  • Colombia
      • Barranquilla, Colombia, 080001
        • Barranquilla, Colombia
      • Bogotá, Colombia, 110231
        • Bogata, Colombia
      • Cali, Colombia, 760042
        • Cali, Colombia
      • Medellín, Colombia, 050021
        • Medelin, Colombia
      • Medellín, Colombia, 50021
        • Medellin, Colombia
  • Japan
      • Fukushima, Japan, 960-1295
        • Fukushima, Japan
      • Miyazaki, Japan, 889-1692
        • Miyazaki, Japan
      • Osaka, Japan, 530-8480
        • Osaka, Japan
      • Osaka, Japan, 540-0006
        • Osaka, Japan
      • Osaka, Japan, 545-8586
        • Osaka, Japan
      • Tokushima, Japan, 770-8503
        • Tokushima, Japan
      • Tokyo, Japan, 101-8309
        • Tokyo, Japan
      • Yamagata, Japan, 990-9585
        • Yamagata, Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 466-8560
        • Nagoya City, Japan
    • Aomori
      • Hirosaki, Aomori, Japan, 036-8563
        • Hirosaki, Japan
    • Chiba
      • Sakura, Chiba, Japan, 285-8741
        • Sakura, Japan
    • Fukui
      • Yoshida-gun, Fukui, Japan, 910-1193
        • Yoshida-gun, Japan
    • Fukuoka
      • Fukuoka, Fukuoka, Japan, 812-0011
        • Fukuoka-shi, Japan
      • Kurume, Fukuoka, Japan, 830-8543
        • Kurume City, Japan
    • Higashi-ku Fukuoka
      • Fukuoka, Higashi-ku Fukuoka, Japan, 811-0213
        • Fukuoka-shi, Japan
    • Hokkaido
      • Asahikawa, Hokkaido, Japan, 078-8510
        • Asahikawa, Japan
    • Hyōgo
      • Amagasaki, Hyōgo, Japan, 660-8550
        • Amagasaki, Japan
    • Ibaraki
      • Mito, Ibaraki, Japan, 310-0845
        • Mito, Japan
    • Kagawa-ken
      • Kita-gun, Kagawa-ken, Japan, 761-0793
        • Kita-gun, Japan
    • Kagoshima-ken
      • Kagoshima, Kagoshima-ken, Japan, 890-8520
        • Kagoshima City, Japan
    • Saitama
      • Tokorozawa-shi, Saitama, Japan, 359-8513
        • Tokorozawa-shi, Japan
    • Tochigi
      • Shimotsuke-shi, Tochigi, Japan, 329-0498
        • Shimotsuke-shi, Japan
    • Tokyo
      • Hachiōji, Tokyo, Japan, 193-0998
        • Hachioji, Japan
      • Meguro-ku, Tokyo, Japan, 152-8902
        • Meguro-ku, Japan
      • Taito-ku, Tokyo, Japan, 111-0051
        • Taito-ku, Japan
    • Yamaguchi
      • Ube-shi, Yamaguchi, Japan, 755-8505
        • Ube-shi, Japan
  • Puerto Rico
      • Arecibo, Puerto Rico, 00612
        • Arecibo, PR
      • San Juan, Puerto Rico, 00921
        • San Juan, Puerto Rico
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85297
        • Gilbert, Arizona
      • Phoenix, Arizona, United States, 85020
        • Phoenix, Arizona
      • Scottsdale, Arizona, United States, 85255
        • Scottsdale, AZ
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Fayetteville, AR
    • California
      • Bakersfield, California, United States, 93309
        • Bakersfield, CA
      • Encino, California, United States, 91436
        • Encino, California
      • Modesto, California, United States, 95356
        • Modesto, CA
      • Mountain View, California, United States, 94040
        • Mountain View, CA
      • Redlands, California, United States, 92374
        • Redlands, CA
      • Sacramento, California, United States, 95825
        • Sacramento, CA
      • Sacramento, California, United States, 95841
        • Sacramento, CA
      • Santa Ana, California, United States, 92705
        • Santa Ana
      • Santa Ana, California, United States, 92705
        • Santa Ana, CA
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Colorado Springs, CO
      • Denver, Colorado, United States, 80012
        • Denver, CO
      • Durango, Colorado, United States, 81303
        • Durango, CO
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Danbury, CT
      • Manchester, Connecticut, United States, 06042
        • Manchester, CT
      • Waterford, Connecticut, United States, 06385
        • Waterford,CT
      • Waterford, Connecticut, United States, 06385
        • Waterford, CT
    • Florida
      • Deerfield Beach, Florida, United States, 33064
        • Deerfield Beach, FL
      • Fort Lauderdale, Florida, United States, 33308
        • Fort Lauderdale, FL
      • Fort Myers, Florida, United States, 33912
        • Fort Myers, FL
      • Gainesville, Florida, United States, 32607
        • Gainesville, FL
      • Orlando, Florida, United States, 32806
        • Orlando, FL
      • Plantation, Florida, United States, 33324
        • Plantation, FL
      • Sarasota, Florida, United States, 34232
        • Sarasota, FL
      • St. Petersburg, Florida, United States, 33711
        • Saint Petersburg, FL
      • Tallahassee, Florida, United States, 32308
        • Tallahassee, FL
      • Tampa, Florida, United States, 33617
        • Tampa, FL
      • Tampa, Florida, United States, 33609
        • Tampa, FL
      • Winter Haven, Florida, United States, 33880
        • Winter Haven, FL
    • Illinois
      • Joliet, Illinois, United States, 60435
        • Joliet, Illinois
      • Lemont, Illinois, United States, 60439
        • Lemont, IL
      • Oak Park, Illinois, United States, 60304
        • Oak Park, IL
      • Springfield, Illinois, United States, 62702
        • Springfield, IL
    • Iowa
      • West Des Moines, Iowa, United States, 50266
        • West Des Moines, IA
    • Kansas
      • Lenexa, Kansas, United States, 66215
        • Lenexa, KS
      • Wichita, Kansas, United States, 67214
        • Wichita, Kansas
    • Maine
      • Portland, Maine, United States, 04101
        • Portland, ME
    • Maryland
      • Baltimore, Maryland, United States, 21209
        • Baltimore, Maryland
      • Hagerstown, Maryland, United States, 21740
        • Hagerstown, MD
      • Towson, Maryland, United States, 21204
        • Towson, MD
    • Massachusetts
      • Springfield, Massachusetts, United States, 01107
        • Springfield,MA
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Grand Rapids, MI
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Edina, MN
      • Minneapolis, Minnesota, United States, 55435
        • Minneapolis, MN
    • Mississippi
      • Madison, Mississippi, United States, 39110
        • Madison, MS
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Henderson, Nevada
    • New Jersey
      • Bloomfield, New Jersey, United States, 07003
        • Bloomfield, NJ
      • Cherry Hill, New Jersey, United States, 08034
        • Cherry Hill, NJ
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Albuquerque, New Mexico
    • New York
      • Great Neck, New York, United States, 11021
        • Great Neck, New York
      • Hauppauge, New York, United States, 11788
        • Hauppauge, New York
      • Liverpool, New York, United States, 13088
        • Liverpool, NY
      • New York, New York, United States, 10022
        • New York, NY
      • Rochester, New York, United States, 14620
        • Rochester, NY
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Asheville, NC
      • Cary, North Carolina, United States, 27511
        • Cary, North Carolina
      • Hickory, North Carolina, United States, 28602
        • Hickory, NC
      • Wake Forest, North Carolina, United States, 27587
        • Wake Forest, NC
      • Winston-Salem, North Carolina, United States, 27103
        • Winston Salem, NC
      • Winston-Salem, North Carolina, United States, 27103
        • Winston-Salem, NC
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74114
        • Tulsa, Oklahoma
    • Oregon
      • Portland, Oregon, United States, 97225
        • Portland, Oregon
      • Portland, Oregon, United States, 97221
        • Portland, OR
      • Salem, Oregon, United States, 97302
        • Salem, Oregon
      • Springfield, Oregon, United States, 97477
        • Springfield, OR
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Bethlehem, PA
      • Erie, Pennsylvania, United States, 16507
        • Erie, PA
    • South Carolina
      • Aiken, South Carolina, United States, 29802
        • Aiken, SC
      • Beaufort, South Carolina, United States, 29902
        • Beaufort, SC
      • Beaufort, South Carolina, United States, 29902
        • Beaufort, NC
      • Bluffton, South Carolina, United States, 29910
        • Bluffton, NC
      • Charleston, South Carolina, United States, 29414
        • Charleston, SC
      • Florence, South Carolina, United States, 29501
        • Florence, SC
      • Ladson, South Carolina, United States, 29456
        • Ladson, SC
      • Ladson, South Carolina, United States, 29456
        • Ladson, NC
      • West Columbia, South Carolina, United States, 29169
        • West Columbia, SC
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Germantown, TN
      • Hixson, Tennessee, United States, 37343
        • Hixson, TN
      • Johnson City, Tennessee, United States, 37604
        • Johnson City, TN
      • Knoxville, Tennessee, United States, 37922
        • Knoxville, TN
      • Nashville, Tennessee, United States, 37203
        • Nashville, TN
    • Texas
      • Abilene, Texas, United States, 79606
        • Abilene, TX
      • Amarillo, Texas, United States, 79106
        • Amarillo, TX
      • Arlington, Texas, United States, 76012
        • Arlington, TX
      • Austin, Texas, United States, 78705
        • Austin, TX
      • Bellaire, Texas, United States, 77401
        • Bellaire, TX
      • Burleson, Texas, United States, 76028
        • Burleson, Texas
      • Dallas, Texas, United States, 75231
        • Dallas, TX
      • Fort Worth, Texas, United States, 76104
        • Fort Worth, TX
      • Katy, Texas, United States, 77494
        • Katy, TX
      • Plano, Texas, United States, 75075
        • Plano, TX
      • Round Rock, Texas, United States, 78681
        • Round Rock, TX
      • San Antonio, Texas, United States, 78240
        • San Antonio, TX
      • San Marcos, Texas, United States, 78666
        • San Marcos, Texas
      • Schertz, Texas, United States, 78154
        • Schertz, TX
      • The Woodlands, Texas, United States, 77384
        • The Woodlands, TX
      • Willow Park, Texas, United States, 76087
        • Willow Park, TX
    • Utah
      • Salt Lake City, Utah, United States, 84107
        • Salt Lake City, UT
      • West Jordan, Utah, United States, 84088
        • West Jordan, Utah
    • Virginia
      • Lynchburg, Virginia, United States, 24502
        • Lynchburg, VA
      • Richmond, Virginia, United States, 23235
        • Richmond, VA
    • Washington
      • Bellevue, Washington, United States, 98004
        • Bellevue, Washington
      • Burlington, Washington, United States, 98233
        • Burlington, Washington
      • Spokane, Washington, United States, 99204
        • Spokane, WA

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

  • Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity
  • Be male or female ≥18 years of age.
  • Have type 1 or type 2 diabetes mellitus and a hemoglobin A1c (HbA1c) of ≤12%.
  • Have a decrease in vision in the study eye determined by the investigator to be primarily the result of diabetic macular edema (DME).

Exclusion Criteria:

  • Be pregnant or breastfeeding
  • History of cataract surgery and/or minimally invasive glaucoma surgery in the study eye within 90 days of Screening
  • Have any treatment for complications of cataract surgery with steroids or yttrium aluminum garnet (YAG) laser capsulotomy within 90 days of Screening
  • Are currently using drugs with known retinal toxicity (e.g., Hydroxychloroquine, pentosan polysulfate sodium, and amiodarone)

  • If treatment-experienced for DME have a history of any of the following treatments within the noted time windows:

    • Have had prior treatment in the study eye with 8 mg aflibercept (EYLEA HD) or faricimab (VABYSMO) within 120 days prior to the Screening visit
    • Have had an IVT with other anti-VEGF treatments (ranibizumab, bevacizumab, aflibercept [2 mg], pegaptanib sodium) in the study eye within 90 days of the Screening visit

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: EYE103 Low Dose Treatment Arm
Drug: EYE103
EYE103 is a humanized antibody formulated for intravitreal administration
Other Names:
  • Restoret
Experimental: EYE103 High Dose Treatment Arm
Drug: EYE103
EYE103 is a humanized antibody formulated for intravitreal administration
Other Names:
  • Restoret
Active Comparator: Ranibizumab Treatment Arm
Drug: Ranibizumab
Ranibizumab is a commercially available anti-VEGF treatment formulated for intravitreal administration for use in patients with diabetic macular edema
Other Names:
  • Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Best-Corrected Visual Acuity (BCVA) measured using the standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) chart
Time Frame: Baseline and Week 52
The change from baseline in Best-Corrected Visual Acuity (BCVA) measured using the standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) chart will be presented.
Baseline and Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants who gain ≥15 ETDRS letters in BCVA at Week 52
Time Frame: Up to approximately Week 52
The proportion of participants who chain ≥15 letters on the standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) chart in Best-Corrected Visual Acuity (BCVA) at Week 52 will be presented.
Up to approximately Week 52
Time to gaining ≥15 ETDRS letters
Time Frame: Up to approximately Week 52
The time to gaining ≥15 letters on the standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) chart will be presented.
Up to approximately Week 52
Change from Baseline in Focal Area Zone (FAZ) area on fluorescein angiography (FA) at Week 52
Time Frame: Baseline and Week 52
The change from baseline in Focal Area Zone (FAZ) area on fluorescein angiography (FA) at Week 52 will be presented.
Baseline and Week 52
Change from Baseline in Optical Coherence Tomography (OCT) Central Subfield Thickness (CST) at Week 52
Time Frame: Baseline and Week 52
The change from baseline in Optical Coherence Tomography (OCT) Central Subfield Thickness (CST) at Week 52 will be presented.
Baseline and Week 52
Superiority Hypothesis: Change from Baseline in ETDRS BCVA at Week 52
Time Frame: Baseline and Week 52
The Superiority Hypothesis: change from baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) at Week 52 will be presented.
Baseline and Week 52
Time to absence of Diabetic Macular Edema (DME)
Time Frame: Up to approximately Week 52
The time to absence of Diabetic Macular Edema (DME) defined as Optical Coherence Tomography (OCT) Central Subfield Thickness (CST) of <300 μm will be presented.
Up to approximately Week 52
Proportion of participants with resolution of macular leakage on FA at Week 24
Time Frame: Up to approximately Week 24
The proportion of participants with resolution of macular leakage on fluorescein angiography (FA), defined as 0 to 1 mm^2, at Week 24 will be presented.
Up to approximately Week 24
Proportion of participants without intraretinal and subretinal fluid at the foveal center on OCT at Week 52
Time Frame: Up to approximately Week 52
The proportion of participants without intraretinal and subretinal fluid at the foveal center on Optical Coherence Tomography (OCT) at Week 52 will be presented.
Up to approximately Week 52
Proportion of participants who gain ≥5 ETDRS letters in BCVA at Week 52
Time Frame: Up to approximately Week 52
The proportion of participants who gain ≥5 letters on the standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) chart in Best-Corrected Visual Acuity (BCVA) at Week 52 will be presented.
Up to approximately Week 52
Proportion of participants achieving 20/40 or better BCVA at Week 52
Time Frame: Up to approximately Week 52
The proportion of participants who achieve 20/40 or better Best-Corrected Visual Acuity (BCVA) at Week 52 will be presented.
Up to approximately Week 52
Number of Participants Who Experience an Ocular and/or Systemic Adverse Event (AE)
Time Frame: Up to approximately 104 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an ocular and/or systemic AE will be reported.
Up to approximately 104 Weeks
Number of Participants Who Experience an Ocular and/or Systemic Serious Adverse Event (SAE)
Time Frame: Up to approximately 104 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an ocular and/or systemic serious adverse event (SAE) will be reported.
Up to approximately 104 Weeks
Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 104 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
Up to approximately 104 Weeks

Collaborators and Investigators

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

Sponsor

EyeBiotech Ltd.

Investigators

  • Study Director: Charles Miller, MD PhD, EyeBiotech 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)

April 16, 2025

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 30, 2028

Study Registration Dates

First Submitted

April 16, 2025

First Submitted That Met QC Criteria

April 25, 2025

First Posted (Actual)

May 4, 2025

Study Record Updates

Last Update Posted (Actual)

June 26, 2026

Last Update Submitted That Met QC Criteria

June 24, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EYE-RES-103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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