Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease
PHOTON
A Randomized, Double-Masked, Active-Controlled Phase 2/3 Study of the Efficacy and Safety of High-Dose Aflibercept in Patients With Diabetic Macular Edema
2 other identifiers
interventional
660
8 countries
138
Brief Summary
The primary objective of the study is to determine if treatment with high-dose aflibercept (HD) at intervals of 12 or 16 weeks provides non-inferior best corrected visual acuity (BCVA) compared to aflibercept dosed every 8 weeks. The secondary objectives of the study are as follows:
- To determine the effect of HD vs. aflibercept on anatomic and other visual measures of response
- To evaluate the safety, immunogenicity, and pharmacokinetics (PK) of aflibercept
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2020
Typical duration for phase_2
138 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2020
CompletedFirst Posted
Study publicly available on registry
June 12, 2020
CompletedStudy Start
First participant enrolled
June 29, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 30, 2022
CompletedResults Posted
Study results publicly available
November 21, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
June 18, 2024
CompletedAugust 8, 2025
July 1, 2025
1.9 years
May 26, 2020
July 25, 2023
July 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48
Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).
Baseline, Week 48
Secondary Outcomes (16)
Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48
Baseline, Week 48
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48
Baseline, Week 48
Percentage of Participants With BCVA ≥69 Letters at Week 48
At Week 48
Percentage of Participants Without Fluid at Foveal Center at Week 48
At Week 48
Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48
Baseline, Week 48
- +11 more secondary outcomes
Study Arms (3)
aflibercept Q8
ACTIVE COMPARATORAdministered every 8 weeks after a loading phase
High-Dose aflibercept Q12
EXPERIMENTALAdministered every 12 weeks after a loading phase
High-Dose aflibercept Q16
EXPERIMENTALAdministered every 16 weeks after a loading phase
Interventions
Intravitreally (IVT) administered as a liquid formulation in a vial
Intravitreally (IVT) administered as a liquid formulation in a vial
Eligibility Criteria
You may qualify if:
- Diabetic macular edema (DME) with central involvement in the study eye
- Best corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye with decreased vision determined to be primarily the result of DME
- Willing and able to comply with clinic visits and study-related procedures
- Provide informed consent signed by study participant or legally acceptable representative
- Extension Phase: All randomized patients that complete visit 26, week 96, as long as the patient 1) provides informed consent and 2) no treatment for DME has been given in the study eye other than the randomized study treatment.
You may not qualify if:
- Evidence of macular edema due to any cause other than diabetes mellitus in either eye
- Active proliferative diabetic retinopathy in the study eye
- IVT anti-VEGF treatment (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) or panretinal laser photocoagulation (PRP) /macular laser photocoagulation within 12 weeks (84 days) or intraocular or periocular corticosteroids within 16 weeks (112 days) of the screening visit in the study eye
- Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy, etc.) at any time
- Treatment with ocriplasmin (JETREA®) in the study eye at any time
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Regeneron Pharmaceuticalslead
- Bayercollaborator
Study Sites (138)
Regeneron Study Site
Phoenix, Arizona, 85021, United States
Regeneron Study Site
Arcadia, California, 91006, United States
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Beverly Hills, California, 90211, United States
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Campbell, California, 95008, United States
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Encino, California, 91436, United States
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Fullerton, California, 92835, United States
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Huntington Beach, California, 92647, United States
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Long Beach, California, 90807, United States
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Palo Alto, California, 94303, United States
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Pasadena, California, 91107, United States
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Poway, California, 92064, United States
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Rancho Cordova, California, 95670, United States
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Riverside, California, 92505, United States
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Torrance, California, 90509, United States
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Colorado Springs, Colorado, 80909, United States
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Durango, Colorado, 81301, United States
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Lakewood, Colorado, 80228, United States
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Waterford, Connecticut, 06385, United States
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Clearwater, Florida, 33761, United States
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Fort Lauderdale, Florida, 33308, United States
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Fort Myers, Florida, 33912, United States
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Jacksonville, Florida, 32216, United States
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Lakeland, Florida, 33805, United States
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Largo, Florida, 33770, United States
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Melbourne, Florida, 32901, United States
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Miami, Florida, 33126, United States
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Orlando, Florida, 32806, United States
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Pinellas Park, Florida, 33782, United States
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Plantation, Florida, 33324, United States
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St. Petersburg, Florida, 33711, United States
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Stuart, Florida, 34994, United States
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Winter Haven, Florida, 33880, United States
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Augusta, Georgia, 30909, United States
Regeneron Study Site 1
Marietta, Georgia, 30060, United States
Regeneron Study Site 2
Marietta, Georgia, 30060, United States
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‘Aiea, Hawaii, 96701, United States
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Oak Forest, Illinois, 60452, United States
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Springfield, Illinois, 62703, United States
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Springfield, Illinois, 62704, United States
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Carmel, Indiana, 46290, United States
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Shawnee Mission, Kansas, 66204, United States
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Baltimore, Maryland, 21209, United States
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Hagerstown, Maryland, 21740, United States
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Boston, Massachusetts, 02114, United States
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Royal Oak, Michigan, 48073, United States
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Southaven, Mississippi, 38671, United States
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Henderson, Nevada, 89052, United States
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Bloomfield, New Jersey, 07003, United States
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Edison, New Jersey, 08820, United States
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Teaneck, New Jersey, 07666, United States
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Great Neck, New York, 11021, United States
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Liverpool, New York, 13088, United States
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New York, New York, 11221, United States
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Oceanside, New York, 11572, United States
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Shirley, New York, 02114, United States
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Asheville, North Carolina, 28803, United States
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Charlotte, North Carolina, 28210, United States
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Beachwood, Ohio, 44122, United States
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Cincinnati, Ohio, 45202, United States
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Cincinnati, Ohio, 45242, United States
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Cleveland, Ohio, 44130, United States
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Dublin, Ohio, 43016, United States
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Edmond, Oklahoma, 73013, United States
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Tulsa, Oklahoma, 74114, United States
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Portland, Oregon, 97225, United States
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Bethlehem, Pennsylvania, 18017, United States
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Kingston, Pennsylvania, 18704, United States
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Monroeville, Pennsylvania, 15146, United States
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Beaufort, South Carolina, 29902, United States
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Ladson, South Carolina, 29456, United States
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West Columbia, South Carolina, 29169, United States
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Rapid City, South Dakota, 57701, United States
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Germantown, Tennessee, 38138, United States
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Knoxville, Tennessee, 37922, United States
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Nashville, Tennessee, 37203, United States
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Abilene, Texas, 79606, United States
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Bellaire, Texas, 77401, United States
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San Antonio, Texas, 78240, United States
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The Woodlands, Texas, 77384, United States
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Willow Park, Texas, 76087, United States
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Salt Lake City, Utah, 84107, United States
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Fairfax, Virginia, 22031, United States
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Norfolk, Virginia, 23502, United States
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Morgantown, West Virginia, 26506, United States
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Calgary, Alberta, T2H 0C8, Canada
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Mississauga, Ontario, L4W 1W9, Canada
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North York, Ontario, M3C 0G9, Canada
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Sherbrooke, Quebec, J1G 2V4, Canada
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Pardubice, 530 02, Czechia
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Prague, 100 34, Czechia
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Prague, 128 08, Czechia
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Prague, 150 00, Czechia
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Neubrandenburg, Mecklenburg-Westfalen, 17036, Germany
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Göttingen, North Rhine-Westphalia, 37075, Germany
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Münster, North Rhine-Westphalia, 48145, Germany
Regeneron Study Site 1
Pécs, Baranya, H-7621, Hungary
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Szombathely, Vas County, H-9700, Hungary
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Zalaegerszeg, Zala County, H-8900, Hungary
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Budapest, H-1085, Hungary
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Budapest, H-1106, Hungary
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Budapest, H-1133, Hungary
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Budapest, H-1145, Hungary
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Debrecen, H-4032, Hungary
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Szeged, H-6720, Hungary
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Nagakute, Aichi-ken, 480-1195, Japan
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Nagoya, Aichi-ken, 466-8560, Japan
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Nagoya, Aichi-ken, 467-8602, Japan
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Yoshida-Gun, Fukui, 910-1193, Japan
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Kurume, Fukuoka, 830-0011, Japan
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Kōriyama, Fukushima, 963-8052, Japan
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Hakodate, Hokkaido, 041-0851, Japan
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Kobe, Hyōgo, 650-0017, Japan
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Mito, Ibaraki, 310-0845, Japan
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Toride, Ibaraki, 302-0014, Japan
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Tsuchiura-shi, Ibaraki, 300-0817, Japan
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Kita-gun, Kagawa-ken, 761-0793, Japan
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Kawasaki, Kanagawa, 216-8511, Japan
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Matsumoto, Nagano, 390-8621, Japan
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Nagasaki, Nagasaki, 852-8501, Japan
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Kashihara, Nara, 634-8522, Japan
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Hirakata, Osaka, 573-1191, Japan
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Tokorozawa, Saitama, 359-8513, Japan
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Susono, Shizuoka, 410-1102, Japan
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Shimotsuke-shi, Tochigi, 329-0498, Japan
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Chiyoda-ku, Tokyo, 101-8309, Japan
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Hachiōji, Tokyo, 193-0998, Japan
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Itabashi-ku, Tokyo, 173-0015, Japan
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Meguro-ku, Tokyo, 152-8902, Japan
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Ube, Yamaguchi, 755-8505, Japan
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Fukuoka, 812-0011, Japan
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Fukuoka, 819-8585, Japan
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Kagoshima, 890-8520, Japan
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Osaka, 545-8586, Japan
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Saitama, 330-8553, Japan
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Tokushima, 770-8503, Japan
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Arecibo, 00612, Puerto Rico
Regeneron Study Site
Sunderland, Tyne and Wear, SR2 9HP, United Kingdom
Regeneron Study Site
London, EC1V 2PD, United Kingdom
Related Publications (3)
Suzuma K, Murata T, Shimura M, Yoshida S, Kishino G, Berliner AJ, Chu KW, Reed K, Vitti R, Cheng Y, Voronca D, Bhore R, Leal S, Morgan-Warren P, Schulze A, Schmidt-Ott U, Kobayashi M, Sakamoto T; PHOTON Investigators. Intravitreal aflibercept 8 mg in patients from Japan with diabetic macular edema: 48-week subgroup analysis of the PHOTON trial. Jpn J Ophthalmol. 2025 Dec 26. doi: 10.1007/s10384-025-01271-7. Online ahead of print.
PMID: 41452566DERIVEDDo DV, Wykoff CC, Sivaprasad S, Brown DM, Boyer DS, Sakamoto T, Win P, Joshi S, Salehi-Had H, Seres A, Berliner AJ, Leal S, Vitti R, Chu KW, Reed K, Cheng Y, Bhore R, Bai Z, Schmidt-Ott U, Schmelter T, Schulze A, Hasanbasic Z, Morgan-Warren PJ, Zhang X, Hirshberg B, Yancopoulos GD; PHOTON Investigators. Intravitreal Aflibercept 8 mg for Diabetic Macular Edema: Ninety-Six-Week Results from the Randomized Phase 2/3 PHOTON Trial. Ophthalmology. 2025 Nov 10:S0161-6420(25)00707-9. doi: 10.1016/j.ophtha.2025.10.028. Online ahead of print.
PMID: 41223900DERIVEDBrown DM, Boyer DS, Do DV, Wykoff CC, Sakamoto T, Win P, Joshi S, Salehi-Had H, Seres A, Berliner AJ, Leal S, Vitti R, Chu KW, Reed K, Rao R, Cheng Y, Sun W, Voronca D, Bhore R, Schmidt-Ott U, Schmelter T, Schulze A, Zhang X, Hirshberg B, Yancopoulos GD, Sivaprasad S; PHOTON Investigators. Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial. Lancet. 2024 Mar 23;403(10432):1153-1163. doi: 10.1016/S0140-6736(23)02577-1. Epub 2024 Mar 7.
PMID: 38461843DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trials Administrator
- Organization
- Regeneron Pharmaceuticals, Inc
Study Officials
- STUDY DIRECTOR
Clinical Trial Management
Regeneron Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 26, 2020
First Posted
June 12, 2020
Study Start
June 29, 2020
Primary Completion
May 30, 2022
Study Completion
June 18, 2024
Last Updated
August 8, 2025
Results First Posted
November 21, 2023
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
- Access Criteria
- Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
All IPD that underlie results in a publication.