A Phase III, Multicenter, Randomized Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Retinopathy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 174
- 试验地点
- 128
- 主要终点
- Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52
研究概览
简要总结
Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm
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)
盲法说明
The visual acuity examiner will only conduct refraction and visual acuity assessments and will be masked, as best as possible, to the following items: study eye assignment; study visit type; and treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years at time of signing Informed Consent Form
- •Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
- •HbA1c level of ≤12% within 2 months prior to screening or at screening
- •Inclusion Criteria for Study Eye
- •Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53)
- •BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better)
排除标准
- •Uncontrolled blood pressure
- •Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
- •Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
- •Current systemic treatment for a confirmed active systemic infection
- •Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
- •History of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the patient at high risk for treatment complications in the opinion of the investigator or Sponsor
- •Ocular Exclusion Criteria for Study Eye:
- •Presence of center-involved diabetic macular edema (defined as CST ≥325 µm)
- •Any intravitreal anti-VEGF treatment at any time prior to randomization
- •Any use of medicated intraocular implants, including Ozurdex® or Iluvien® implants at any time prior to randomization
- •Any intravitreal corticosteroid treatment at any time prior to randomization
- •Any periocular (e.g., subtenon) corticosteroid treatment at any time prior to randomization
- •Any PRP at any time prior to randomization
- •Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any time prior to randomization
- •Active intraocular inflammation (grade trace or above)
- •Clinically significant abnormalities of the vitreous-retinal interface involving the macular area or disrupting the macular architecture, such as vitreous-retinal traction or epiretinal membrane (assessed by the investigator and confirmed by the central reading center)
- •Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study
- •History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- •Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would require surgical intervention during the study to prevent or treat visual loss that might result from that condition
- •Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect interpretation of study results
- •History of other ocular diseases that gives reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of study results, or that renders the participant at high risk for treatment complications
- •Ocular Exclusion Criteria for Either Eye
- •Suspected or active ocular or periocular infection of either eye
- •Any history uveitis including idiopathic, drug-associated or autoimmune-associated uveitis
研究组 & 干预措施
PDS Arm
Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 36-weeks (Q36W) thereafter
干预措施: Intravitreal Ranibizumab 0.5 mg Injection (Drug)
PDS Arm
Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 36-weeks (Q36W) thereafter
干预措施: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab (Drug)
Comparator Arm
Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.
干预措施: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab (Drug)
Comparator Arm
Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.
干预措施: Intravitreal Ranibizumab 0.5 mg Injection (Drug)
结局指标
主要结局
Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52
时间窗: Baseline, Week 52
ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The Cochran-Mantel Haenszel (CMH) method was used for analysis and weighted percentage of participants are estimated and reported in this outcome measure. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. SD OCT= spectral-domain optical coherence tomography.
次要结局
- Time to First Development of CI-DME(Baseline up to Week 112)
- Time to First Development of a ≥ 2-Step Worsening From Baseline on the ETDRS-DRSS(Baseline up to Week 112)
- Time to First Development of PDR or ASNV(Baseline up to Week 112)
- Rate of Participants Developing a Vision-Threatening Complication or Center-involved Diabetic Macular Edema (CI-DME) Through Week 52(From Baseline through Week 52)
- Rate of Participants Developing PDR or ASNV Through Week 52(From Baseline through Week 52)
- Rate of Participants Developing CI-DME Through Week 52(From Baseline through Week 52)
- Rate of Participants Developing a ≥ 2-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52(From Baseline through Week 52)
- Percentage of Participants With a ≥ 3-Step Improvement From Baseline on the ETDRS-DRSS at Week 52(Week 52)
- Rate of Participants Developing a ≥ 3-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52(From Baseline through Week 52)
- Percentage of Participants With a ≥ 2-Step Improvement From Baseline on the ETDRS-DRSS Over Time(Baseline up to Week 112)
- Percentage of Participants With a ≥ 3-step Improvement From Baseline on the ETDRS-DRSS Over Time(Baseline up to Week 112)
- Time to First Development of Either PDR, ASNV, or CI-DME(Baseline up to Week 112)
- Time to First Development of a ≥ 3-Step Worsening From Baseline on the ETDRS-DRSS(Baseline up to Week 112)
- Change From Baseline in Best-Corrected Visual Acuity (BCVA) as Measured on the ETDRS Chart Over Time(Baseline up to Week 112)
- Percentage of Participants Who Lost <15, <10 and <5 Letters in BCVA From Baseline Over Time(Baseline up to Week 112)
- Percentage of Participants With a BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time(Baseline up to Week 112)
- Change From Baseline in CST as Measured on SD-OCT Over Time(Baseline up to Week 112)
- Change From Baseline in Total Macular Volume (TMV) as Measured on SD-OCT Over Time(Baseline up to Week 112)
- Number of Participants With Ocular Adverse Events (AEs) and Severity of Ocular AEs in the PDS Arm(From first dose of study drug through Week 52)
- Number of Participants With Non-ocular AEs in the PDS Arm(From first dose of study drug through Week 52)
- Number of Participants With At Least One Ocular Adverse Events of Special Interest (AESI) in the PDS Arm(From first dose of study drug through Week 52)
- Number of Participants With At Least One Ocular AESI During the Postoperative Period in the PDS Arm(From Day 1 to Day 37 Postoperative Period)
- Serum Concentration of Ranibizumab Observed Over Time(Baseline up to week 112)
- Pharmacokinetic (PK) Parameter Value Area Under the Concentration(At Baseline and multiple time points up to week 112)
- Minimum Serum Concentration (Cmin) of Ranibizumab Observed Over Time(Baseline up to week 112)
- Half-Life (t ½) of Ranibizumab Observed Over Time(Baseline up to Week 112)
- Number of Participants With Anti-Drug Antibodies (ADAs) to Ranibizumab(Baseline up to Week 112)
- Number of Participants With Neutralizing Antibodies to Ranibizumab(Baseline up to Week 112)
- Percentage of Participants Who do Not Undergo Supplemental Treatment With Intravitreal Ranibizumab Within Each Refill-Exchange Interval(Baseline up to Week 112)
- Percentage of Participants With At Least One AE Related to Study Device or Procedure in the PDS Arm(From first dose of study drug through Week 52)
- Percentage of Participants With Serious Adverse Effects Related to Study Device or Procedure in the PDS Arm(From Day 1 up to Week 52)
- Percentage of Participants With Absence of Intraretinal Fluid, Subretinal Fluid or Both Over Time(Baseline up to Week 112)
- Percentage of Participants Who Report Preferring PDS Treatment to Intravitreal Ranibizumab Treatment, as Measured by the PDS Patient Preference Questionnaire (PPPQ) at Week 52(Week 52)
- Number of Participants With Device Deficiencies(Baseline up to Week 52)