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OpenTrials
Completed

NCT Number: NCT04429503

Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease

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

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Key information

Conditions

Diabetic Macular Edema Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Regeneron Study Site, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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

NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Treatment and study plan

aflibercept

Drug

Intravitreally (IVT) administered as a liquid formulation in a vial

Other names: EYLEA®, BAY86-5321

High-dose aflibercept

Drug

Intravitreally (IVT) administered as a liquid formulation in a vial

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

    Time frame: Baseline, 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).

Secondary outcomes

  1. Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48

    Time frame: Baseline, Week 48

    The DRSS was assessed according to the following scale: 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Micro-aneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.

  2. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48

    Time frame: Baseline, 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). Only one study eye per participant was analyzed within the study

  3. Percentage of Participants With BCVA ≥69 Letters at Week 48

    Time frame: 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).

  4. Percentage of Participants Without Fluid at Foveal Center at Week 48

    Time frame: At Week 48

    Retinal fluid status was evaluated using spectral domain optical coherence tomography (SD-OCT) on the study eye.

  5. Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48

    Time frame: Baseline, Week 48

    Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

  6. Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48

    Time frame: At Week 48

    Leakage is the release of fluorescein dye from diseased retinal vessels.

  7. Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48

    Time frame: Baseline, Week 48

    Vision-specific quality of life is assessed with the NEI VFQ-25 (National Eye Institute Visual Function Questionnaire), i.e. a 25-item questionnaire that gives a score on a scale from 0 (worst) to 100 (best = no vision problems).

  8. Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48

    Time frame: Through Week 48

    Concentrations of Free Aflibercept in Plasma by Time and Treatment Group

  9. Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA

    Time frame: Baseline, 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). (Per Statistical Analysis Plan (SAP) Version 2.0 Appendix 10.9 for US Only)

  10. Change From 8-weeks Post Initial Treatment Phase in BCVA in the Study Eye in Participants With Both 8-weeks Post Initial Treatment Phase BCVA and Week 48 BCVA

    Time frame: Baseline, 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). (Per SAP Version 2.0 Appendix 10.9 for US Only)

  11. Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60

    Time frame: Baseline, Week 60

    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).

  12. Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96

    Time frame: Through Week 96

    Number of participants with pre-existing immunoreactivity and treatment-emergent ADA response reported

  13. Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96

    Time frame: Through Week 96

    A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.

  14. Number of Participants With Any Serious TEAE Through Week 96

    Time frame: Through Week 96

    A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.

  15. Number of Participants With Any TEAE Through Week 156

    Time frame: Through Week 156

    TEAEs are defined as AEs starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days or week 156 visit, whichever was later.

  16. Number of Participants With Any Serious TEAE Through Week 156

    Time frame: Through Week 156

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Collaborators

  • Bayer

Registry information

Official study title

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

Acronym: PHOTON

Important dates

Study start
2020
Primary completion
2022
Study completion
2024
First posted
Jun 12, 2020
Registry last updated
Aug 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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