NCT05126966撤回3 期
A Phase IIIb, Multicenter, Randomized, Visual Assessor-Masked Study Of The Effectiveness And Safety Of A 36-Week Refill Regimen For The Port Delivery System With Ranibizumab Vs Aflibercept Treat & Extend In Subjects With Neovascular Age-Related Macular Degeneration
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 10
- 主要终点
- Change from baseline in BCVA score at week 80 as assessed using the ETDRS visual acuity chart at a starting distance of 4 meters
研究概览
简要总结
This study will evaluate the effectiveness and safety of a 36-week refill regimen for the Port Delivery System with ranibizumab 100 mg/mL (PDS Q36W) compared with intravitreal injections of aflibercept (2 mg) administered per treat-and-extend (aflibercept T&E) in subjects with neovascular (wet) age-related macular degeneration (nAMD).
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 (Outcomes Assessor)
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
- •Signed Informed Consent Form
- •Age ≥ 50 years, at time of signing Informed Consent Form
- •Ability and willingness to undertake all scheduled visits and assessments
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
- •Ocular Inclusion Criteria:
- •Initial diagnosis of nAMD within 9 months prior to the screening visit
- •Previous treatment with at least three anti-VEGF intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit
- •Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis
- •Availability of historical visual acuity data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
- •Availability of historical SD-OCT image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
- •BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using ETDRS chart at a starting distance of 4 meters (see the BCVA manual for additional details) at screening and randomization visits
- •With any subtype of nAMD lesions (i.e., type I, type II, type III, or mixed forms per OCT classification, including polypoidal choroidal vasculopathy and retinal angiomatous proliferation)
- •Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical examination and analysis and grading by the central reading center of fundus photography (FP), FA, fundus autofluorescence (FAF) image, and SD-OCT images
排除标准
- •Prior Ocular Treatment - Study Eye
- •History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
- •Prior pars plana vitrectomy surgery
- •Prior treatment with Visudyne® (verteporfin for injection), external-beam radiation therapy, or transpupillary thermotherapy
- •Previous treatment with corticosteroid intravitreal injection
- •Previous intraocular device implantation (not including intraocular lens implants)
- •Previous intraocular surgery (including cataract surgery) within 3 months of randomization
- •Previous laser (any type) used for AMD or diabetic retinopathy treatment
- •History of vitreous hemorrhage
- •History of rhegmatogenous retinal detachment
- •Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant
- •History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- •History of corneal transplant
- •History of conjunctival surgery in the superotemporal quadrant (including pterygium surgery)
- •Prior Ocular Treatment Either Eye:
- •History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the ranibizumab or aflibercept injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anesthetic and antimicrobial preparations used by a subject during the study
- •Any contraindication to aflibercept as per local label
- •Prior participation in a clinical trial involving any anti-VEGF drugs within 6 months prior to the randomization visit
- •Prior treatment with brolucizumab (at any time prior to the screening visit)
- •Prior treatment with external-beam radiation therapy or brachytherapy
- •MNV (CNV) Lesion Characteristics Study Eye:
- •Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5-disc area (1.27 mm^2) in size at screening
- •Subfoveal fibrosis or subfoveal atrophy
- •MNV (CNV) Lesion Characteristics Either Eye:
- •CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio retinopathy, or pathologic myopia
- •CNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)
- •Concurrent Ocular Conditions Study Eye :
- •Subfoveal and/or juxtafoveal retinal pigment epithelial tear
- •Scleral pathology in the superotemporal quadrant (e.g., scleral thinning or calcification)
- •Conjunctival pathologies (e.g., pterygium, scarring, thinning, fibrosis) in the superotemporal quadrant
- •Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, epiretinal membrane, amblyopia, or strabismus) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results
- •Active intraocular inflammation (grade trace or above)
- •Rhegmatogenous retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within 3 months prior to the randomization visit
- •Aphakia or absence of the posterior capsule Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of yttrium-aluminum garnet (YAG) laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
- •Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia or evidence of pathologic myopia on depressed fundus exam
- •Preoperative refractive error that exceeds 8 diopters of myopia, for subjects who have undergone prior refractive or cataract surgery in the study eye
- •Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia
- •Preoperative refractive error that exceeds 5 diopters of hyperopia, for subjects who have undergone prior refractive or cataract surgery
- •Uncontrolled ocular hypertension or glaucoma (defined as intraocular pressure [IOP] > 25 mmHg or a cup to disc ratio > 0.8, despite treatment with anti-glaucoma medication) and any such condition the investigator determines may require a glaucoma-filtering surgery during a subject's participation in the study
- •History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis
- •Ectropion, entropion, ingrowing lashes, or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure
- •Corneal neuropathy
- •Lagophthalmos or incomplete blink
- •Active or history of facial nerve palsy/paresis
- •Concurrent Ocular Conditions Non-Study (Fellow) Eye
- •Non-functioning non-study eye, defined as either:
- •BCVA of hand motion or worse
- •No physical presence of non-study eye (i.e., monocular)
- •Legally blind in the subject's relevant jurisdiction
- •Concurrent Ocular Conditions Either Eye
- 另有 23 项未显示
研究组 & 干预措施
Ranibizumab
Experimental
Subjects will have the implant (filled intra-operatively prior to implantation with approximately 20 µL of the 100-mg/mL formulation of ranibizumab [approximately 2-mg dose of ranibizumab]) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Subjects will have their implant refilled with ranibizumab at weeks 36 and 72.
干预措施: Ranibizumab (Drug)
Ranibizumab
Experimental
Subjects will have the implant (filled intra-operatively prior to implantation with approximately 20 µL of the 100-mg/mL formulation of ranibizumab [approximately 2-mg dose of ranibizumab]) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Subjects will have their implant refilled with ranibizumab at weeks 36 and 72.
干预措施: Port Delivery System with ranibizumab (PDS) (Device)
Aflibercept
Active Comparator
Subjects will receive intravitreal injections of aflibercept (2mg) administered in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment.
干预措施: Aflibercept (Drug)
结局指标
主要结局
Change from baseline in BCVA score at week 80 as assessed using the ETDRS visual acuity chart at a starting distance of 4 meters
时间窗: From baseline up to 80 weeks
\*Depending on the T\&E schedule, some subjects in the comparator arm will have a visit at Week 76 and some at Week 78. All subjects in both arms will have a Week 80 visit
Treatment burden as assessed by the treatment frequency up to Week 80
时间窗: From baseline up to 80 weeks
Treatments include injections and refills.
次要结局
- Proportion of subjects with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better averaged over Weeks 76 (or 78*) and 80(Baseline, Week 76, Week 78, Week 80)
- Proportion of subjects with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse averaged over Weeks 76 (or 78*) and 80(Baseline, Week 76, Week 78, Week 80)
- Change from baseline in center subfield thickness (CST), defined as the average thickness of the central 1 mm circle of the ETDRS grid centered on the fovea measured between the internal limiting membrane and the Bruch's membrane, on SD-OCT at Week 80(Baseline, Week 80)
- Proportion of subjects randomized to PDS Q36W who do not undergo supplemental treatment with intravitreal ranibizumab 0.5 mg before each refill-exchange procedure(Baseline, Week 80)
- Incidence and severity of ocular and systemic (non-ocular) adverse events(Baseline, Week 80)
- Proportion of subjects who lose < 15, < 10, or < 5 letters in BCVA score from baseline averaged over Weeks 76 (or 78*) and 80(Baseline, Week 76, Week 78, Week 80)
- Change from baseline in center point thickness (CPT) at Week 80(Baseline, Week 80)
- Incidence and severity of adverse device effects with PDS Q36W(Baseline, Week 80)
- Incidence, severity, and duration of adverse events of special interest, including ocular adverse events of special interest(Baseline, Week 80)
- Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days of initial implantation) and follow-up period (> 37 days after implantation surgery)(Baseline, Week 80)
- Incidence, causality, severity, and duration of anticipated serious adverse device effects with PDS Q36W(Baseline, Week 80)
研究者
研究点 (10)
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