A Phase II, Multicenter, Randomized, Active Treatment-Controlled Study of the Efficacy and Safety of the Ranibizumab Port Delivery System for Sustained Delivery of Ranibizumab in Patients With Subfoveal Neovascular Age-Related Macular Degeneration
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 225
- 试验地点
- 50
- 主要终点
- Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria
研究概览
简要总结
This is a Phase II multicenter, dose-ranging, randomized, active treatment (monthly ITV injection)-controlled study to evaluate the efficacy, safety, and pharmacokinetics of ranibizumab delivered through the Implant using three ranibizumab formulation arms (10 mg/mL, 40 mg/mL, and 100 mg/mL) compared with the control arm (0.5-mg monthly ITV injections of 10-mg/mL formulation) in participants with subfoveal neovascular 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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Newly diagnosed with wet AMD within 9 months of screening visit
- •Participant must have received at least 2 prior ITV anti-vascular endothelial growth factor (VEGF) injections. However, the most recent anti-VEGF injection must have been ranibizumab and must have occurred at least 7 days prior to the screening visit
- •Demonstrated response to prior ITV anti-VEGF treatment
- •Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts of 20/20-20/200 Snellen equivalent
排除标准
- •Treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
- •Study eye treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
- •History of laser photocoagulation, Visudyne®, ITV corticosteroid injection, vitrectomy surgery, submacular surgery, device implantation, or other surgical intervention for AMD in the study eye
- •Prior participation in a clinical trial involving anti-angiogenic drugs, other than ranibizumab, in either eye within 2 months of the randomization visit
- •Subretinal hemorrhage in the study eye that involves the center of the fovea
- •Subfoveal fibrosis, or atrophy in the study eye
- •Choroidal neovascularization (CNV) in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
- •Uncontrolled ocular hypertension or glaucoma in the study eye
- •History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in the study eye
- •Uncontrolled blood pressure
- •Uncontrolled atrial fibrillation within 3 months of informed consent
- •History of myocardial infarction or stroke within the last 3 months prior to informed consent
- •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 ranibizumab or placement of the Implant, that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications
- •Use of oral corticosteroids
- •Current treatment for any active systemic infection
- •Use of anticoagulants, anti-platelets (other than aspirin), or medications known to exert similar effects
- •Active malignancy within 12 months of randomization
- •History of allergy to fluorescein
- •Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
研究组 & 干预措施
Port Delivery System with Ranibizumab 10mg/mL
Participants had the Implant (prefilled with approximately 20 μL of 10-mg/mL ,approximately 0.2 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 10-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria.
干预措施: Ranibizumab (Drug)
Port Delivery System with Ranibizumab 40mg/mL
Participants had the Implant (prefilled with approximately 20 μL of 40-mg/mL, approximately 0.8 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 40-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria.
干预措施: Ranibizumab (Drug)
Port Delivery System with Ranibizumab 100mg/mL
Participants had the Implant (prefilled with approximately 20 μL of 100-mg/mL, approximately 2 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 100-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria.
干预措施: Ranibizumab (Drug)
Intravitreal Injection with Ranibizumab 0.5mg
Participants received ranibizumab 0.5 mg monthly ITV injections of 10 mg/mL formulation at Day 1 and every month thereafter.
干预措施: Ranibizumab (Drug)
结局指标
主要结局
Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria
时间窗: Baseline up to approximately 38 months
Protocol-Defined Refill Criteria At 1 month after initial fill: * Decrease of ≥ 10 letters in BCVA at the current visit compared with the baseline BCVA, due to nAMD disease activity OR * Increase in CFT of ≥ 100 um at the current visit compared with the baseline CFT, due to nAMD disease activity OR * Presence of new macular hemorrhage, due to nAMD disease activity For subsequent assessments: * Increase in CFT of ≥ 75 μm on SD-OCT at the current visit compared with the average CFT over the last 2 available measurements, due to nAMD disease activity OR * Increase in CFT of ≥ 100 um from the lowest CFT measurement on study, due to nAMD disease activity OR * Decrease of ≥ 5 letters in BCVA at the current visit compared with the average BCVA over the last 2 available measurements, due to nAMD disease activity OR * Decrease of ≥ 10 letters from best recorded BCVA on study, due to nAMD disease activity OR * Presence of new macular hemorrhage, due to nAMD disease activity
次要结局
- Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10(Baseline, Months 9, 10)
- Number of Implant Clogging at Month 9(Month 9)
- Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs)(Baseline up to approximately Month 38)
- Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT)(Baseline up to Month 9)
- Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab(Predose (0 hour) on Day 1 up to 38 months)
- Time to Maximum Concentration (Tmax) of Ranibizumab(Predose (0 hour) on Day 1 up to 38 months)
- Change From Baseline in BCVA Over Time(Baseline up to Month 10)
- Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis)(Baseline up to Month 10)
- Observed Maximum Serum Concentration (Cmax) of Ranibizumab(Predose (0 hour) on Day 1 up to 38 months)
- Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab(Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field))
- Terminal Half-Life (t1/2) of Ranibizumab(Predose (0 hour) on Day 1 up to 38 months)
- Percentage of Participants With Positive Serum Antibodies to Ranibizumab(Baseline up to 38 months)