Brolucizumab vs. Aflibercept for Retinal Angiomatous Proliferation - Prospective Randomised Study
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Best corrected visual acuity
研究概览
简要总结
This is a prospective randomised study comparing two intravitreal antiVEGF drugs - brolucizumab and aflibercept - in the treatment of retinal angiomatous proliferation (RAP). Patients with RAP confirmed on optical coherence tomography (OCT) and on OCT angiography (OCTA) will be randomised in two groups and followed for 52 weeks.
Patients in the first group will receive aflibercept - 3 injections monthly for the first 3 months and then in treat-and-extend regimen with minimal interval of 8 weeks and maximal interval of 16 weeks. Extension or shortening of the therapeutic interval will be possible in 2 or 4 week increments based on the visual acuity and disease activity assessed on OCT.
Patients in the second group will receive brolucizumab - 3 injections monthly in the first 3 months and then every 2 or 3 months based on the visual acuity and disease activity assessed on OCT.
Best corrected visual acuity (BCVA), central retinal thickness (CRT) on OCT and number of injections will be compared between both groups.
详细描述
Retinal angiomatous proliferation (RAP) is one of the variants of wet form of age-related macular degeneration (wAMD). Neovascularization in RAP grows from the retinal deep capillary plexus into the subretinal space where it forms subretinal and later choroidal neovascularization. It is often accompanied with high macular edema and pigment epithelium detachment (PED). As with other forms of wAMD, treatment with intravitreal antiVEGF drugs is highly effective. In our study, we would like to compare the efficacy of 2 antiVEGF drugs - aflibercept and brolucizumab - in the treatment of RAP.
This is a prospective, randomised, comparative study comparing the best corrected visual acuity (BCVA) and central retinal thickness (CRT) on optical coherence tomography (OCT) in the 16th, 26th and 52nd week of the study between patients with RAP treated with aflibercept and brolucizumab. In the 52nd week, the total number of injections between both groups will be also compared.
Visit plan:
Screening visit - 14 to 1 day prior to baseline. Informed consent will be signed prior to any other study procedures. Ocular and medical history will be written down. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT and OCTA of both eyes will be performed. Colour fundus photograph (FP) and red-free (RF) FP of the macula of both eyes will be performed. Based on the examination results, patients eligibility for the study will be assessed.
Baseline - day 1 - VFQ-25 questionnaire will be done with the patient. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Based on the examination results, patients eligibility for the study will be assessed. Eligible patients will be randomised and study medication will be given.
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
- Single (Participant)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age of 50 years or more at the time the informed consent is signed
- •active RAP in the macula including fovea diagnosed on OCT and OCTA
- •BCVA between 70 to 35 ETDRS letters (approx. 20/40 to 20/200 Snellen equivalent)
- •decrease in BCVA caused primarily by the RAP in the study eye
- •presence of intra- or subretinal fluid or PED in the central 1 mm of the macula on the OCT
- •patient capable of signing the informed consent
排除标准
- •other causes of choroidal neovascular membrane (CNV) than wAMD
- •previous or current conditions of the study eye:
- •subretinal haemorrhage comprising more than 25% of the lesion in the study eye
- •scar or fibrosis comprising more than 50% of the lesion in the study eye
- •presence of retinal pigment epithelium (RPE) tears or ruptures in the central 1 mm of the macula in the study eye
- •total lesion size more than 8 papillary diameters (PD) as per OCT and FP examination
- •uncontrolled glaucoma in the study eye defined as IOP of more than 25 mmHg despite the antiglaucoma treatment
- •idiopathic or autoimmune uveitis in the study eye
- •other pathologies in the macula of the study eye which can be expected to influence the BCVA (e.g. macular hole, retinal atrophy, epiretinal membrane, etc.)
- •history of glaucoma surgery in the study eye or probability that it will be necessary in the future
- •aphakia or pseudophakia with absence of the posterior lens capsule (with the exception of missing posterior capsule due to Nd:YAG laser capsulotomy) in the study eye
- •myopia in the study eye with spherical equivalent of more than 8 dioptries before any refractive or cataract surgery
- •significant opacities of the ocular media in the study eye including cataract, which can interfere with BCVA assessment or FP or OCT examination
- •corneal transplantation or corneal dystrophy in the study eye
- •irregular astigmatism or BCVA-lowering amblyopia in the study eye
- •diabetic retinopathy, diabetic macular edema or any other retinal vascular disease in the study eye
- •extraocular or periocular infection or inflammation (e.g. blepharitis, keratitis, conjunctivitis, scleritis, etc.) in any eye at the time of screening or baseline visit
- •any intraocular infection or inflammation in any eye during 12 weeks (84 days) before the screening visit
- •allergy or hypersensitivity to any component contained in the study drug
- •pregnant or breastfeeding women
研究组 & 干预措施
aflibercept
Patients with RAP who will be receiving aflibercept.
干预措施: Aflibercept 40 MG/ML [Eylea] (Drug)
aflibercept
Patients with RAP who will be receiving aflibercept.
干预措施: Ranibizumab 6 MG/ML [Lucentis] (Drug)
brolucizumab
Patients with RAP who will be receiving brolucizumab.
干预措施: Brolucizumab-Dbll 120 MG/ML [Beovu] (Drug)
brolucizumab
Patients with RAP who will be receiving brolucizumab.
干预措施: Ranibizumab 6 MG/ML [Lucentis] (Drug)
结局指标
主要结局
Best corrected visual acuity
时间窗: Baseline and week 52
BCVA change from baseline to week 52.
Number of injections
时间窗: Week 52
Average number of injections per patient in each group.
Central retinal thickness
时间窗: Baseline and week 52
CRT change from baseline to week 52.
次要结局
- Rescue(Week 52)
- Dry macula(Week 52)
- Significant visual gain(Week 52)
- Significant visual loss(Week 52)
- Adverse events(Week 52)
研究者
Martin Pencak
Principal Investigator
Faculty Hospital Kralovske Vinohrady