A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of the Port Delivery System With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration (Portal)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 291
- 主要终点
- Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)
研究概览
简要总结
This study will evaluate the long-term safety and tolerability of the Port Delivery System with ranibizumab (PDS) (100 mg/mL) in participants with neovascular age-related macular degeneration (nAMD) who have either completed Phase II Study GX28228 (Ladder), Phase III Study GR40548 (Archway), Phase IIIb Study WR42221 (Velodrome), or completed Week 24 visit in Study WR42221 but were not eligible to be randomized in WR42221.
详细描述
The Transscleral Photocoagulation sub-study (sub-study 1) will evaluate the effectiveness of using transscleral photocoagulation (TPC) with the Iridex laser system to mitigate vitreous hemorrhages secondary to the Port Delivery System with ranibizumab (PDS) implantation procedure in participants with neovascular age-related macular degeneration (nAMD). The sub-study will enroll about 55 participants.
The Re-implantation sub-study (sub-study 2) will evaluate the safety of re-implantation with the updated PDS with ranibizumab . Up to 100 participants who previously participated in the main study in the United States will be enrolled and followed for a maximum of 72 weeks post-re-implantation in the substudy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The sub-study 1 and sub-study 2 are open-label studies.
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
- •Previous enrollment in and completion of Study GX28228 (Ladder) or Study GR40548 (Archway), without early treatment or study discontinuation in either study OR Previous enrollment in Study WR42221 (Velodrome) and either not eligible to be randomized in Study WR42221 at Week 24 or completed the study (from the Q24W or Q36W arm)
- •Ability and willingness to undertake all scheduled visits and assessments
- •For women of childbearing potential: agreement to remain abstinent or use contraceptive measures
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last intravitreal injection of ranibizumab or 1 year after the last Implant refill-exchange of ranibizumab
- •History of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of the results of the study or that renders the participant at high risk for treatment complications
- •History of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or that renders the participant at high risk of treatment complications
- •Requirement for continuous use of any medications or treatments indicated in the "Prohibited Therapy"
- •Sub-study 1
- •Inclusion Criteria
- •- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
- •Participants must meet the following ocular criteria for the study eye for substudy entry:
- •Diagnosis of exudative nAMD within 2 years prior to the enrollment visit
- •Previous treatment with at least two anti-VEGF ITV injections (e.g., ranibizumab, bevacizumab, or aflibercept) for nAMD per standard of care within 6 months prior to the enrollment visit
- •Demonstrated response to prior anti-VEGF ITV treatment since diagnosis, as evidenced at enrollment by the following:
- •Overall decrease in nAMD disease activity detected on SD-OCT AND Stable or improved best-corrected visual acuity (BCVA)
- •All subtypes of nAMD lesions are permissible (i.e., type I, type II, type III, or mixed forms per optical coherence tomography (OCT) classification) nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea).
- •Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of FP and SD-OCT images.
- •Exclusion Criteria Prior Ocular Treatments Study Eye
- •History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
- •Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
- •Previous treatment with corticosteroid ITV injection
- •Previous intraocular device implantation
- •Previous laser (any type) used for AMD treatment
- •Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the enrollment visit
- •Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the enrollment visit, other than ranibizumab
- •CNV Lesion Charateristics Study Eye
- •Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 mm2 ) in size at screening
- •Subfoveal fibrosis or subfoveal atrophy
- •- CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
- •Concurrent Ocular Conditions Study Eye
- •Retinal pigment epithelial tear
- •Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) 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)
- •History of vitreous hemorrhage
- •History of rhegmatogenous retinal detachment
- •History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment 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
- •Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery in the study eye
- •Intraocular surgery (including cataract surgery) within 3 months preceding the enrollment visit
- •Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
- •History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- •History of corneal transplant
- •History of prior vitrectomy surgery and absence of posterior capsule
- •History of idiopathic or autoimmune-associated uveitis
- •Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
- •Concurrent Systemic Conditions
- •Inability to comply with study schedule or procedures as described in the study protocol
- •Uncontrolled blood pressure
- •History of stroke within the last 3 months prior to informed consent
- •Uncontrolled atrial fibrillation within 3 months of informed consent
- •History of myocardial infarction within the last 3 months prior to informed consent
- 另有 31 项未显示
研究组 & 干预措施
Sub-study 2: Cohort 2a
Participants who received an updated PDS implant, have < 24 weeks post-re-implantation follow-up and no refill exchange visit in the main study, will undergo two refill-exchange procedures with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
Sub-study 2: Cohort 2b
Participants who received an updated PDS implant, have < 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, will undergo one refill-exchange procedure with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 6 (ex-US only)
Participants from Study WR42221 randomized to the Q24W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 7 (ex-US only)
Participants from Study WR42221 randomized to the Q36W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q36W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
Sub-study 1: PDS Implant
Participants will receive PDS implant using TPC on Day 1 followed by refill-exchanges of ranibizumab 100 mg/mL via the PDS Q24W.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 3 (US only)
Participants in the intravitreal ranibizumab arm of Study GX28228 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240.
Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 4 (US only)
Participants in the intravitreal ranibizumab arm of Study GR40548 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240.
Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 1 (US only)
Participants with PDS implant from Study GX28228 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240.
Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 2 (US only)
Participants with PDS implant from Study GR40548 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240.
Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
PDS Implant Cohort 5 (ex-US only)
Participants from Study WR42221 who completed Week 24 but were not eligible to be randomized within WR42221 and who will be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
Sub-study 2: Cohort 1
Participants will undergo re-implantation with the updated PDS implant and receive 2 refill-exchanges of ranibizumab 100 mg/mL Q24W.
干预措施: PDS Implant with Ranibizumab 100 mg/mL (Drug)
结局指标
主要结局
Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)
时间窗: Baseline up to Week 240
Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs)
时间窗: Baseline up to Week 240
Incidence, Severity, and Duration of PDS-Associated Ocular AESIs During the Postoperative Period (Up to 37 days of Initial Implantation) and Follow-Up Period (>37 days After Implantation Surgery) for Participants who Receive the PDS Implant in the Study
时间窗: Baseline up to Week 240
Incidence and Severity of Adverse Device Effects
时间窗: Baseline up to Week 240
Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects
时间窗: Baseline up to Week 240
Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery.
时间窗: Baseline to Week 4
Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs
时间窗: Baseline to Week 72
Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs
时间窗: Baseline to Week 72
Sub-study 2: Duration of AESIs
时间窗: Baseline to Week 72
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period
时间窗: Up to Day 37 post re-implantation
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period
时间窗: > 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Duration of Ocular AESIs During the Post-operative Period
时间窗: Up to Day 37 post re-implantation
Sub-study 2: Duration of Ocular AESIs During the Follow-up Period
时间窗: > 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEs
时间窗: Baseline to Week 72
Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs
时间窗: Baseline to Week 72
Sub-study 2: Duration of Anticipated Serious ADEs
时间窗: Baseline to Week 72
Sub-study 2: Number of Device Deficiencies
时间窗: Baseline to Week 72
次要结局
- Sub-study 1: Incidence of Ocular Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) in the Study eye(Baseline up to Week 104)
- Sub-study 1: Time From Surgery to Vitreous Hemorrhage Resolution in the Study eye(Baseline up to Week 104)
- Sub-study 1: Incidence of Vitreous Hemorrhage Grade 3 and Higher in the Study eye over time(Baseline up to Week 104)
- Sub-study 1: Distribution of Vitreous Hemorrhage Grade in the Study eye Over Time(Baseline up to Week 104)
- Sub-study 1: Rate of Vitrectomy in the Study eye(Baseline up to Week 104)
- Sub-study 1: Change From Baseline in Center Subfield Thickness (CST) Over Time(Baseline up to Week 104)
- Sub-study 2: Number of Participants with Ocular AESIs and Severity of AESIs Following Refill-exchange(Up to approximately Week 72)
- Sub-study 2: Duration of AESIs Following Refill-exchange(Up to approximately Week 72)
- Sub-study 2: Number of Participants With ADEs and Severity of ADEs Following Refill-exchange(Up to approximately Week 72)
- Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs Following Refill-exchange(Up to approximately Week 72)
- Sub-study 2: Number of Device Deficiencies Following Refill-exchange(Up to approximately Week 72)
- Change in Best-Corrected Visual Acuity (BCVA) Score from Baseline Over Time, as Assessed using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters(Baseline up to Week 240)
- Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time(Baseline up to Week 240)
- Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over Time(Baseline up to Week 240)
- Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over Time(Baseline up to Week 240)
- Change from Baseline in Center Point Thickness (CPT) Over Time(Baseline up to Week 240)
- Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange Interval(Baseline up to Week 240)
- Sub-study 1: Incidence of AEs Commonly Seen After Transscleral Cyclophotocoagulation (TS-CPC) for Treatment of Glaucoma in the Study eye(Baseline up to Week 104)
- Sub-study 1: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score From Baseline Over Time(Baseline up to Week 104)
- Sub-study 1: Change in BCVA Score From Baseline Over Time(Baseline up to Week 104)
- Sub-study 1: Change from Baseline in CPT Over Time(Baseline up to Week 104)