Proliferative Diabetic Retinopathy (PDR)
Conditions
Keywords
HERO, PDR
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.
Interventions
DRUGAflibercept 8mg
Solution in Vial, intravitreal (IVT) injection
Sponsors
Edward Wood, MD
Greater Houston Retina Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Any 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 (90 days) wash-out period for anti-VEGF allowed) * Any intra- or periocular corticosteroid treatment in the study eye within 3 months (90 days) of baseline * Any intraocular sustained-release treatment or implantable device in the study eye * 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 (precluding baseline imaging and DRSS grading) * Presence of any tractional retinal detachment (macular or peripheral) or pre-retinal fibrovascular proliferation (macular or peripheral) causing definite retinal traction or elevation (e.g. retinal tenting/peaking, tractional folds, or OCT-confirmed tractional distortion) in the study eye. Pre-retinal fibrovascular tissue without evidence of retinal traction or elevation (macular or peripheral) is permitted * 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, or total abstinence). * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| DRSS Step Improvement | Baseline to week 24 and 96 | Proportion of eyes with ≥ 2 step improvement in diabetic retinopathy severity scale (DRSS), as assessed by the central reading center |
| Mean change in BCVA | Baseline through weeks 24, 48, 72, and 96 | Evaluate the mean change in the best corrected visual acuity (BCVA) |
| 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) |
| Changes in visual function on HVF | Baseline to weeks 48, 96. | Mean change in Humphrey visual field 30-2 total point score |
| CST change | Baseline to weeks 24, 48, 72, 96 | Mean change in CST |
| 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 |
| Worsening PDR | Baseline to week 96 | Time to first worsening of proliferative diabetic retinopathy associated event(s), including PDR-related vitrectomy, new or worsening preretinal or vitreous hemorrhage, retinal detachment, panretinal photocoagulation (time-to-event analysis) |
| CI-DME development | Baseline to week 96 | ·Time to first development of central-involved DME (CI-DME) defined as \> 320 µm in the study eye (time-to-event analysis) |
| AEs notated | Baseline to week 96 | Incidence and severity of ocular and systemic adverse events |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREdward Wood, MD
Retina Consultants of Texas
Outcome results
None listed