A Phase II, Multicenter, Randomized, Double Masked, Active Comparator-Controlled Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7200220 in Combination With Ranibizumab 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
- 187
- 试验地点
- 37
- 主要终点
- Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants
研究概览
简要总结
Study BP43464 is a phase II, multicenter, randomized, double-masked active comparator-controlled study designed to assess the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of vamikibart in combination with, anti-vascular endothelial growth factor (VEGF) inhibitor, ranibizumab compared with ranibizumab alone in participants with diabetic macular edema. Only one eye will be chosen as the study eye. The duration of the study will be 76 weeks.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Diagnosis of diabetes mellitus (Type 1 or Type 2)
- •Macular thickening secondary to diabetic macular edema (DME) involving the center of the macula
- •Decreased visual acuity attributable primarily to DME
- •Ability and willingness to provide written informed consent and to comply with the study protocol
- •Willingness to allow Aqueous Humor collection
- •For women of childbearing potential: agreement to remain abstinent or use at least one highly effective contraceptive method that results in a failure rate of <1% per year during the treatment period and for at least 12 weeks after the final dose of study treatment
排除标准
- •Hemoglobin A1c (HbA1c) of greater than (>) 12%
- •Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest
- •Currently pregnant or breastfeeding, or intend to become pregnant during the study
- •Prior treatment with panretinal photocoagulation or macular laser to the study eye
- •Any intraocular or periocular corticosteroid treatment within the past 16 weeks prior to Day 1 to the study eye
- •Prior Iluvien or Retisert implants within 3 years prior to Day 1 to the study eye
- •Prior or concomitant treatment with anti-VEGF therapy within 8 weeks prior to Day 1 to the study eye; Vabysmo^TM within 16 weeks prior to Day 1, prior Beovu® is not permitted
- •Prior administration of IVT brolucizumab (Beovu®): ever; vamikibart: </=24 weeks prior to Day 1) in either eye
- •Any proliferative diabetic retinopathy
- •Active intraocular or periocular infection or active intraocular inflammation in the study eye
- •Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye
- •Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye
- •Other protocol-specified inclusion/exclusion criteria may apply
研究组 & 干预措施
Arm A: Vamikibart + Ranibizumab
Participants will receive vamikibart, 1 milligram (mg) administered as intravitreal (IVT) injection in combination with ranibizumab, 0.5 mg IVT, on Day 1 and every fourth week (Q4W) up to Week 44, for a total of 12 injections, followed by an observational period up to Week 72.
干预措施: Vamikibart (Drug)
Arm A: Vamikibart + Ranibizumab
Participants will receive vamikibart, 1 milligram (mg) administered as intravitreal (IVT) injection in combination with ranibizumab, 0.5 mg IVT, on Day 1 and every fourth week (Q4W) up to Week 44, for a total of 12 injections, followed by an observational period up to Week 72.
干预措施: Ranibizumab (Drug)
Arm B: Ranibizumab
Participants will receive ranibizumab, 0.5 mg IVT, from Day 1 and Q4W in combination with sham up to Week 44, for a total of 12 injections, followed by an observational period up to Week 72.
干预措施: Ranibizumab (Drug)
Arm B: Ranibizumab
Participants will receive ranibizumab, 0.5 mg IVT, from Day 1 and Q4W in combination with sham up to Week 44, for a total of 12 injections, followed by an observational period up to Week 72.
干预措施: Sham Procedure (Other)
结局指标
主要结局
Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants
时间窗: Baseline, Week 44 and Week 48
BCVA was measured via Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity (VA) examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a Mixed Model for Repeated Measurements (MMRM) model.
次要结局
- Number of Participants With Systemic and Ocular Adverse Events (AEs)(Up to Week 72)
- Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Previously Treated Participants(Baseline, Week 44 and Week 48)
- Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Overall ITT Population(Baseline, Week 44 and Week 48)
- Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Treatment-naïve Participants(Baseline, Week 32 and Week 36)
- Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants(Baseline, Week 32 and Week 36)
- Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall ITT Population(Baseline, Week 32 and Week 36)
- Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Treatment-naïve Participants(Baseline, Week 20 and Week 24)
- Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Previously Treated Participants(Baseline, Week 20 and Week 24)
- Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall ITT Population(Baseline, Week 20 and Week 24)
- Change From Baseline in BCVA Over Time in Overall ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Change From Baseline in CST Averaged Over Week 20 and Week 24 in Overall ITT Population(Baseline, Week 20 and Week 24)
- Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population(Up to Week 72)
- Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population(Up to Week 72)
- Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time(Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time(Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time(Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Change From Baseline in Central Subfield Thickness (CST) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants(Baseline, Week 44 and Week 48)
- Change From Baseline in CST Averaged Over Week 44 and Week 48 in Previously Treated Participants(Baseline, Week 44 and Week 48)
- Change From Baseline in CST Averaged Over Week 44 and Week 48 in Overall ITT Population(Baseline, Week 44 and Week 48)
- Change From Baseline in CST Averaged Over Week 32 and Week 36 in Treatment-naïve Participants(Baseline, Week 32 and Week 36)
- Change From Baseline in CST Averaged Over Week 32 and Week 36 in Previously Treated Participants(Baseline, Week 32 and Week 36)
- Change From Baseline Averaged Over Week 32 and Week 36 in Overall ITT Population(Baseline, Week 32 and Week 36)
- Change From Baseline in CST Averaged Over Week 20 and Week 24 in Treatment-naïve Participants(Baseline, Week 20 and Week 24)
- Change From Baseline in CST Averaged Over Week 20 and Week 24 in Previously Treated Participants(Baseline, Week 20 and Week 24)
- Change From Baseline in CST Over Time in Overall ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Percentage of Participants With Absence of DME Over Time in Overall ITT Population(Baseline, Weeks 4, 8, 12, 16, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population(Baseline, Weeks 4, 12, 24, 36, 48, and 72)
- Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population(Baseline, Weeks 4, 12, 24, 36, 48, and 72)