A 96-week, Single-arm Study to Evaluate the Efficacy and Safety of 8mg Aflibercept in Subjects With Proliferative Diabetic Retinopathy (PDR) Without Center-involved Diabetic Macular Edema (DME)
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Primary Endpoint - DRSS step improvement
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
All subjects
Subjects will receive 8mg aflibercept at week 0, 4, and 8. At week 12, 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: administer IVT aflibercept 8mg at 4-week intervals. If NV is not assessable due to VH, continue IVT and reassess; PRP is deferred.
Supplemental PRP permitted ONLY if NV is assessable AND "No Regression" persists after prespecified treatment thresholds.
Partial regression: Continue IVT aflibercept 8mg. Continue monthly observation. PRP not permitted.
Total Regression: Without IVT aflibercept 8mg. Continue monthly observation. PRP not permitted.
干预措施: Aflibercept 8mg (Drug)
结局指标
主要结局
Primary Endpoint - DRSS step improvement
时间窗: 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
次要结局
- DRSS Step Improvement(Baseline to weeks 24, 48, 72, 96)
- Number of supplemental treatments(Baseline through week 96)
- Mean change in BCVA(Baseline through weeks 24, 48, 72, and 96)
- CST change(Baseline to weeks 24, 48, 72, 96)
- Conversion from PDR to NPDR(Baseline to weeks 24, 48, 72, 96.)
- Retinal non-perfusion change(Baseline to weeks 24, 48, 72, 96.)
- AEs notated(Baseline to week 96)
- Changes in visual function on HVF(Baseline to weeks 48, 96.)
- CI-DME development(Baseline to week 96)
- Worsening PDR(Baseline to week 96)
- DRSS Step Improvement(Baseline to week 24 and 96)
研究者
Edward Wood, MD
Principal Investigator
Greater Houston Retina Research