NCT04702048撤回4 期
The Evaluation of Retinal PhotoReceptors And Vasculature in Moderate and Severe Non-proliferative Diabetic Retinopathy Patients After Intravitreal Aflibercept on Using Adaptive Optics Imaging Study (PRAVA) Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Mean change in photoreceptor cell density
研究概览
简要总结
The purpose of this study is to specifically assess the effect of intravitreal aflibercept injections on the health of cells and the flow of blood through the retinal blood vessels by using advanced technology called adaptive optics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
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
- •Documented Type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR (DRSS levels 47 or 53) as confirmed by 2 independent physician evaluators.
- •Age ≥18 years
- •Willingness and the ability to provide signed informed consent, comply with clinic visits and study-related procedure, and provide Health Insurance Portability and Accountability Act authorization
- •BCVA of ≥ 73 letters, inclusive (≥20/40 approximate Snellen equivalent), using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA manual for additional details) on Day 1
- •Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality CFPs (including ETDRS 7 modified fields or Optos ultra-widefield image to permit grading of diabetic retinopathy and assessment of the retina) and other imaging modalities, including AOSLO.
- •No center-involved macular edema (defined as fluid within 1000 microns of the fovea)
- •HbA1c of ≤10% within 2 months prior to the first injection visit date
- •For men* and women** of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; 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 amenorrheic 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.
排除标准
- •Presence of DME threatening the center of the macula (within 1,000 microns of the foveal center) in the study eye
- •Evidence of retinal neovascularization on clinical examination or FA
- •Any prior focal or grid laser photocoagulation (within 1,000 microns of the foveal center) or any prior PRP in the study eye
- •Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
- •Any prior intraocular steroid injection in the study eye
- •History of vitreoretinal surgery in the study eye
- •Intraocular pressure (IOP) ≥25 mm Hg in the study eye
- •Evidence of active infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye
- •Any intraocular inflammation or infection in either eye within 3 months of the screening visit
- •Current Anterior segment neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
- •Ocular media of insufficient quality to obtain fundus and optical coherence tomography (OCT), and adaptive optics images in the study eye
- •Hemoglobin A1c (HbA1c) >12%, or if HbA1c is ≤12%, diabetes mellitus is uncontrolled in the opinion of the investigator
- •Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of IVT injections, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety
- •Uncontrolled blood pressure (defined as systolic >160 mm Hg or diastolic >95 mm Hg while patient is sitting)
- •History of cerebrovascular accident or myocardial infarction within 6 months of day 1
- •Renal failure, dialysis, or history of renal transplant
- •Positive serum hCG/urine pregnancy test at the screening or baseline visit
- •History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk for treatment complications
- •Participation as a patient in any interventional ocular clinical study within the 12 weeks prior to day 1 of the study
- •Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; 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 amenorrheic 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
Aflibercept injection
Experimental
Intravitreal injection of Aflibercept
干预措施: Aflibercept Injection (Drug)
Sham injection
Placebo Comparator
Empty syringe with no needle
干预措施: Sham injection (Drug)
结局指标
主要结局
Mean change in photoreceptor cell density
时间窗: baseline to 52 weeks
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells per square micron of image will be quantified at baseline and 52 weeks.
Mean change in photoreceptor cell spacing
时间窗: baseline to 52 weeks
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and a measurement of the space between photoreceptor cells will be calculated at baseline and 52 weeks.
Mean change in photoreceptor mosaic
时间窗: baseline to 52 weeks
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells will be quantified at baseline and 52 weeks.
次要结局
- Percent of participants with a non-ocular adverse events(52 weeks)
- Mean change in foveal avascular zone area(baseline to 52 weeks)
- Mean change in blood cell flux(baseline to 52 weeks)
- Change in duration of capillary occlusions(baseline to 52 weeks)
- Mean change in number of capillary occlusions(baseline to 52 weeks)
- Proportion of patients with a ≥ 2-step DRS improvement from baseline on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS DRSS)(52 weeks)
- Mean change in capillary blood cell velocity(baseline to 52 weeks)
- Percent of participants with a severe ocular adverse events(52 weeks)
- Percent of participants with a severe non-ocular adverse events(52 weeks)
- Mean change in macular retina non-perfusion area(baseline to 52 weeks)
- Proportion of patients with a ≥ 3-step DRS improvement from baseline on the ETDRS DRSS.(52 weeks)
- Mean change in central subfield thickness(baseline to 52 weeks)
- Proportion of patients with absence of intraretinal fluid(52 weeks)
- Mean change in mean parafoveal macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness(baseline to 52 weeks)
- Mean change in Best Corrected Visual Acuity (BCVA)(baseline to 52 weeks)
- Percent of participants with any ocular adverse events(52 weeks)
- Change in proportion of patients with BCVA Snellen equivalent of 20/40 or better(baseline to 52 weeks)
- Proportion of participants who receive intravitreal aflibercept(week 52)
- Proportion of participants developing a vision-threatening complication due to diabetic retinopathy(52 weeks)
- Proportion of patients with absence of subretinal fluid(52 weeks)
- Proportion of participants who receive panretinal photocoagulation (PRP)(week 52)
研究者
Jesse Schallek
Assistant Professor
University of Rochester
研究点 (1)
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