A Phase III, Multicenter, Randomized, Visual Assessor-masked, Active-comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Chinese Patients With Neovascular Age-related Macular Degeneration
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 68
- 试验地点
- 44
- 主要终点
- Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Averaged Over Weeks 36 and 40, as Assessed Using the ETDRS Visual Acuity (VA) Chart at a Starting Distance of 4 Meters
研究概览
简要总结
This study will evaluate the efficacy, safety, and PK of ranibizumab 100 milligrams per milliliter (mg/mL) delivered every 24 weeks (Q24W) via the PDS implant compared with ranibizumab 0.5 milligrams (mg) delivered every 4 weeks (Q4W) as intravitreal (IVT) injection in Chinese participants with 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
- •Initial diagnosis of nAMD within 9 months prior to the screening visit
- •Previous treatment with at least three anti-vascular endothelial growth factor (VEGF) IVT injections for nAMD per standard-of-care (SOC) within 6 months prior to the screening visit
- •Demonstrated response to prior anti-VEGF IVT treatment since diagnosis
- •Availability of historical VA data prior to the first anti-VEGF treatment for nAMD up to the screening visit
- •BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters
- •All subtypes of nAMD lesions are permissible
- •Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) images
排除标准
- •A. Prior Ocular Treatment Study Eye
- •History of vitrectomy surgery, submacular surgery, or other surgical intervention, all for AMD
- •Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
- •Previous treatment with corticosteroid IVT injection or corticosteroid implants
- •Previous intraocular device implantation (not including intraocular lens implants)
- •Previous laser (any type) used for age-related macular degeneration (AMD) treatment
- •Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
- •Prior treatment with IVT treatments for geographic atrophy
- •Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant
- •Prior treatment with brolucizumab
- •Prior gene therapy for nAMD or other ocular diseases
- •Previous participation in any ocular disease studies of investigational drugs and/or devices, within 3 months or five elimination half-lives of the investigational therapy, whichever is longer, preceding the screening visit
- •B. Choroidal Neovascularization (CNV) Lesion Characteristics
- •Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 millimeter square [mm^2]) in size at screening
- •Subfoveal fibrosis or subfoveal atrophy
- •Either Eye • CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia
- •C. Concurrent Ocular Conditions Study Eye
- •Retinal pigment epithelial tear
- •Any concurrent intraocular condition
- •Active intraocular inflammation (grade trace or above)
- •History of vitreous hemorrhage
- •History of rhegmatogenous retinal detachment
- •History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the randomization visit
- •History of pars plana vitrectomy surgery
- •Aphakia or absence of the posterior capsule
- •Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia
- •Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery
- •Intraocular surgery (including cataract surgery) within 3 months preceding the randomization visit
- •Uncontrolled ocular hypertension or glaucoma
- •History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- •History of corneal transplant
- •Fellow (Non-Study) Eye
- •Non-functioning fellow eye
- •Any history of uveitis
- •Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
研究组 & 干预措施
Implant Arm
Participants will have the implant (pre-filled intraoperatively with ranibizumab 100 mg/mL) surgically inserted on Day 1. After Day 1, participants in the implant arm will attend monthly study visits, and receive implant refill-exchanges with ranibizumab 100 mg/mL at Week 24 and Week 48. At the Week 48 study visit, participants will move to the long -term extension phase of the study and continue receiving refill-exchanges Q24W until the end of study. Participants will attend monthly visits up to Week 96 and bi-monthly visits thereafter, followed by visits every two months until study completion.
干预措施: PDS With Ranibizumab (100 mg/mL) (Device)
IVT Arm
Participants will receive IVT ranibizumab 0.5 mg injections starting on Day 1. Participants will receive IVT ranibizumab 0.5 mg Q4W until Week 44. At the Week 48 study visit, participants will receive the PDS implant (pre-filled intraoperatively with ranibizumab 100 mg/mL), move to the long-term extension phase of the study and receive Q24W refill exchanges until the end of study. If participants are unable to attend the Week 48 visit due to extenuating circumstances, they should return no later than the next scheduled visit (Week 52), when they will receive the PDS implant. Participants will attend monthly visits up to Week 96 and bi-monthly visits thereafter, followed by visits every two months until study completion.
干预措施: Ranibizumab (10 mg/mL) (Drug)
IVT Arm
Participants will receive IVT ranibizumab 0.5 mg injections starting on Day 1. Participants will receive IVT ranibizumab 0.5 mg Q4W until Week 44. At the Week 48 study visit, participants will receive the PDS implant (pre-filled intraoperatively with ranibizumab 100 mg/mL), move to the long-term extension phase of the study and receive Q24W refill exchanges until the end of study. If participants are unable to attend the Week 48 visit due to extenuating circumstances, they should return no later than the next scheduled visit (Week 52), when they will receive the PDS implant. Participants will attend monthly visits up to Week 96 and bi-monthly visits thereafter, followed by visits every two months until study completion.
干预措施: PDS With Ranibizumab (100 mg/mL) (Device)
结局指标
主要结局
Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Averaged Over Weeks 36 and 40, as Assessed Using the ETDRS Visual Acuity (VA) Chart at a Starting Distance of 4 Meters
时间窗: Baseline up to Week 40
次要结局
- Change From Baseline in BCVA Score Over Time(Baseline up to Week 144)
- Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 36 and 40(Baseline up to Week 40)
- Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 44 and 48(Baseline up to Week 48)
- Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged over Weeks 36 and 40(Baseline up to Week 40)
- Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged Over Weeks 44 and 48(Baseline up to Week 48)
- Proportion of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40(Baseline up to Week 40)
- Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48(Baseline up to Week 48)
- Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40(Baseline up to Week 40)
- Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48(Baseline up to Week 48)
- Change From Baseline in Center Point Thickness (CPT) at Week 36(Baseline, Week 36)
- Change From Baseline in Central Subfield Thickness (CST) at Week 36(Baseline, Week 36)
- Change From Baseline in CPT at Week 44(Baseline, Week 44)
- Change From Baseline in CST at Week 44(Baseline, Week 44)
- Proportion of Participants in the Implant Arm Who do not Undergo Supplemental Treatment With IVT Ranibizumab 0.5 mg Before the First, Second, Third, Fourth, Fifth, and Sixth Fixed Refill-exchange Intervals(Baseline up to 144 weeks)
- Proportion of Participants in the Implant Arm Who do not Undergo a Supplemental Treatment that Requires Subsequent Additional Supplemental Treatments During the Study(Baseline up to 144 weeks)
- Percentage of Participants With Adverse Events (AEs)(Baseline up to 144 weeks)
- Percentage of Participants With Adverse Events of Special Interest (AESIs)(Baseline up to 144 weeks)
- Percentage of Participants With Ocular AESIs During the Post-operative Period and Follow-up Period(Post-operative period: up to 37 days after initial implantation Follow-up period: > 37 days after implantation surgery (up to 144 weeks))
- Percentage of Participants Who Received PDS Affected With Adverse Device Effects (ADEs)(Baseline up to 144 weeks)
- Percentage of Participants Who Received PDS Affected With Anticipated Serious Adverse Device Effects (ASADEs)(Baseline up to 144 weeks)
- Number of Device Deficiencies(Baseline up to 144 weeks)
- Observed Serum Ranibizumab Concentrations at Specified Timepoints(Baseline, Weeks 4, 12, 24, 28, 36, 48)
- Area Under the Concentration Time Curve From 0-24 Weeks(Baseline, Weeks 4, 12, 24)
- Maximum Serum Concentration of Ranibizumab(Baseline, Weeks 4, 12, 24, 28, 36, 48)
- Minimum serum concentration of ranibizumab(Baseline, Weeks 4, 12, 24, 28, 36, 48)
- Number of Participants With Anti-drug Antibodies (ADAs)(Baseline, Weeks 4, 24, 48)
- Number of Participants With Treatment-emergent ADAs During the Study(Baseline, Weeks 4, 24, 48)