High Dose Eylea for Proliferative Diabetic Retinopathy Outcomes

Not Applicable

Not yet recruiting

• Conditions: Proliferative Diabetic Retinopathy (PDR)
• Interventions: Drug: Aflibercept 8mg

• Registration Number: NCT07118670
• Lead Sponsor: Edward Wood, MD

Brief Summary

The purpose of this Phase 4 study is to evaluate the safety of aflibercept 8mg in patients with proliferative diabetic retinopathy without center-involved diabetic macular edema.

Detailed Description

Subjects will be administered intravitreal aflibercept 8mg every 4 weeks, starting at week 0 for 8 weeks, then may be extended by 4-week intervals with no maximum between treatments with an end of study visit at week 96. At any visit, it will be determined if supplemental treatment is needed as determined by disease activity assessment until there is no regression of disease is noted and the extension intervals will begin again.

Study Timeline

• Study First Submitted: 2025-07-29
• Status Verified: 2025-08
• Study First Submitted QC: 2025-08-07
• Last Update Submitted: 2025-08-07
• Study First Posted: 2025-08-12
• Last Update Posted: 2025-08-12
• Study Start: 2025-08-31
• Primary Completion: 2027-11
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent
• Men or women > 18 years of age at the time of signing the Informed Consent Form
• Diagnosed with type 1 or type 2 diabetes mellitus
• BCVA ETDRS >/= 20/400 in the study eye
• Proliferative Diabetic Retinopathy as diagnosed via clinical examination and fluorescein angiography

Exclusion Criteria

• Any known hypersensitivity to any of the components of aflibercept 8 mg injection

• Any known hypersensitivity to any contrast media (e.g., fluorescein), dilating eye drops, disinfectants (e.g., iodine), or any of the anesthetics and antimicrobial preparations used bye the site during the study

• Prior systemic anti-VEGF or IVT anti-VEGF treatment in the study eye within 3 months of enrollment. (i.e., 3-month wash-out period for anti-VEGF allowed)

• Any intra- or periocular corticosteroid treatment in the study eye within 3 months of baseline

• Any intraocular sustained-release treatment or implantable device

• Any gene therapy in the study eye

• SD-OCT central subfield thickness measurement of > 320 µm, in the study eye

• Evidence of ocular infection, in the study eye, at time of screening

• IOP > 25 mmHg in the study eye

• Any intraocular inflammation/ infection in either eye within 12 weeks (84 days) of the screening visit

• History of vitreoretinal surgery in the study eye

• Any prior Panretinal laser photocoagulation (PRP) in the study eye

• Current vitreous hemorrhage obscuring clear view of the macula in the study eye

• Presence of tractional retinal detachment and/or pre-retinal fibrosis causing retinal elevation/ thickening

• Cataract surgery in the study eye within 4 weeks prior to Screening/ Day 0

• Blood pressure > 180/100 mmHg systolic/ diastolic, while seated

• Pregnant or breastfeeding women

• Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening/ baseline; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly).

  • Contraception is not required for men with documented vasectomy

    • Postmenopausal women must be amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All subjects	Aflibercept 8mg	Subjects will receive 8mg aflibercept at week 0, 4, and 8. At week 8, subjects will enter a variable treatment and extension approach where they may be extended by 4-week intervals with no maximum interval between treatments until the end of study visit at week 96. Supplemental: Disease activity will be assessed at every 4-week visit and supplemental treatment with panretinal photocoagulation (PRP) as needed and/or intravitreal (IVT) 8mg aflibercept injections as determined by the regression patterns listed below. No regression: subjects will receive 8mg aflibercept and PRP every 4 weeks until they exhibit total regression, whereafter they may be re-extended. Partial regression: subjects will receive 8mg aflibercept every 8 weeks and not be extended until total regression is exhibited.

Primary Outcome Measures

Name	Time	Method
Primary Endpoint - DRSS step improvement	Baseline through weeks 48 and 96	Proportion of eyes with ≥ 2 step improvement in diabetic retinopathy severity scale (DRSS), as assessed by the central reading center

Secondary Outcome Measures

Name	Time	Method
DRSS Step Improvement	Baseline to weeks 24, 48, 72, 96	Proportion of eyes with \>= 3 step improvement in diabetic retinopathy severity scale (DRSS)
Number of supplemental treatments	Baseline through week 96	Mean and median number of intravitreal (IVT) 8mg aflibercept injections (with and without intravitreal 8 mg aflibercept injections given for DME) as well as annualized injection frequencies
Mean change in BCVA	Baseline through weeks 24, 48, 72, and 96	Evaluate the mean change in the best corrected visual acuity (BCVA)
CST change	Baseline to weeks 24, 48, 72, 96	Mean change in CST
Conversion from PDR to NPDR	Baseline to weeks 24, 48, 72, 96.	Proportion of eyes converting from proliferative diabetic retinopathy (PDR) to non-proliferative diabetic retinopathy (NPDR)
Retinal non-perfusion change	Baseline to weeks 24, 48, 72, 96.	Mean change (quantitative area) in retinal vascular non-perfusion (RNP) based on ultrawide-field fluorescein angiography (UWFA)
CI-DME development	Baseline to week 96	Mean time to development of central-involved DME (CI-DME)
AEs notated	Baseline to week 96	Incidence and severity of ocular and systemic adverse events
Changes in visual function on HVF	Baseline to weeks 48, 96.	Mean change in Humphrey visual field 30-2 total point score
Worsening PDR	Baseline to week 96	Mean time to development of worsening proliferative diabetic retinopathy associated event/s, including PDR-related vitrectomy, new or worsening preretinal or vitreous hemorrhage, retinal detachment, panretinal photocoagulation