A Multiple-Center, Multiple-Dose, Randomized, Active Comparator-Controlled, Double-Masked, Parallel Group, 36-Week Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO6867461 Administered Intravitreally in Patients With Diabetic Macular Edema
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 229
- 试验地点
- 59
- 主要终点
- Mean Change From Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants
研究概览
简要总结
This is a multiple-center, multiple-dose, randomized, active comparator-controlled, double-masked, three parallel group, 36-week study in participants with center-involving diabetic macular edema (DME). Only one eye will be selected as the study eye. Where both eyes meet all eligibility criteria, the eye with the worse best corrected visual acuity (BCVA) will be defined as the study eye. The study will consist of a treatment period (20 weeks) and an observational period (up to 16 weeks). Treatment naive participants will be randomized in a 1:1:1 ratio to one of the Arms A, B and C, respectively. Participants previously treated with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) will be randomized in a 1:1 ratio to Arms A and C.
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
- Double (Participant, Investigator)
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
- •Macular edema associated with diabetic retinopathy
- •Decreased visual acuity attributable primarily to DME
- •Diagnosis of diabetes mellitus
排除标准
- •High risk proliferative diabetic retinopathy
- •Cataract surgery within 3 months of Baseline, or any other previous intraocular surgery
- •Uncontrolled glaucoma
- •Current or history of ocular disease in the study eye other than DME
- •Major illness or major surgical procedure within 1 month prior to Day 1
- •Uncontrolled blood pressure
- •Glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%) at screening
- •Untreated diabetes mellitus or initiation of oral anti-diabetic medication or insulin within 4 months prior to Day 1
研究组 & 干预措施
Arm A: 0.3 mg Ranibizumab
Participants will receive 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.
干预措施: Ranibizumab (Drug)
Arm B: 1.5 mg Faricimab
Participants will receive 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.
干预措施: Faricimab (Drug)
Arm C: 6 mg Faricimab
Participants will receive 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.
干预措施: Faricimab (Drug)
结局指标
主要结局
Mean Change From Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants
时间窗: Baseline, Week 24
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
次要结局
- Mean Change From Baseline in BCVA Letter Score at Week 24, in All Participants(Baseline, Week 24)
- Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Previously Treated Participants(Week 24)
- Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Previously Treated Participants(Week 24)
- Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in All Participants(Week 24)
- Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Treatment-Naive Participants(Week 24)
- Mean Change From Baseline in the Size of the Foveal Avascular Zone at Week 24, in All Participants(Baseline, Week 24)
- Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants(Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36)
- Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Previously Treated Participants(Baseline up to Week 24)
- Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in All Participants(Baseline up to Week 24)
- Mean Change From Baseline in BCVA Letter Score at Week 24, in Previously Treated Participants(Baseline, Week 24)
- Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Previously Treated Participants(Baseline, Week 24)
- Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in All Participants(Baseline, Week 24)
- Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants(Week 24)
- Mean Plasma Concentrations of Ranibizumab (Arm A) or Faricimab (Arms B and C) Over Time, in All Participants(Predose at Baseline and Weeks 1, 4, 12, 20, 24, 26, 28, 32, and 36)
- Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants(Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36)
- Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Treatment-Naive Participants(Baseline, Week 24)
- Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Treatment-Naive Participants(Week 24)
- Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants(Week 24)
- Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants(Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36)
- Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Treatment-Naive Participants(Week 24)
- Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in All Participants(Week 24)
- Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Treatment-Naive Participants(Baseline, Week 24)
- Mean Change From Baseline in Central Subfield Thickness at Week 24, in Treatment-Naive Participants(Baseline, Week 24)
- Mean Change From Baseline in Central Subfield Thickness at Week 24, in All Participants(Baseline, Week 24)
- Mean Change From Baseline in Central Subfield Thickness at Week 24, in Previously Treated Participants(Baseline, Week 24)
- Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants(Week 24)
- Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Previously Treated Participants(Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36)
- Safety Summary of the Number of Participants With at Least One Adverse Event During the Treatment Period (up to Week 24), in All Participants(From Baseline up to Week 24)
- Number of Participants With Abnormal Diastolic Blood Pressure Over Time, in All Participants(Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36)
- Number of Participants With Marked Laboratory Abnormalities in Hematology Tests, in All Participants(Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks))
- Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants(Week 24)
- Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Previously Treated Participants(Week 24)
- Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Treatment-Naive Participants(Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36)
- Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye During the Treatment Period by Highest Intensity, in All Participants(From Baseline up to Week 24)
- Number of Participants With an Abnormal Heart Rate Over Time, in All Participants(Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36)
- Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants(Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36)
- Safety Summary of the Number of Participants With at Least One Adverse Event During the Post-Treatment Observation Period, in All Participants(From Week 24 up to Week 36)
- Number of Participants With Abnormal Systolic Blood Pressure Over Time, in All Participants(Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36)
- Mean PR, RR, QT, QRS, QTcB, and QTcF Intervals at Baseline and Week 24, as Measured by Electrocardiogram in All Participants(Baseline, Week 24)
- Number of Participants With at Least One Systemic Adverse Event During the Treatment Period by Highest Intensity, in All Participants(From Baseline up to Week 24)
- Number of Participants With Abnormal Body Temperature Over Time, in All Participants(Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36)
- Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants(Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks))
- Mean Heart Rate at Baseline and Week 24, as Measured by Electrocardiogram in All Participants(Baseline, Week 24)
- Number of Participants Who Tested Negative or Positive for Anti-Drug Antibodies Against Faricimab Over Time(Baseline and Weeks 1, 4, 12, 16, 20, 24, 26, 28, 32, and 36)
- Number of Participants With Marked Laboratory Abnormalities in Coagulation Tests, in All Participants(Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks))