A 96-week, Two-arm, Randomized, Single-masked, Multi-center, Phase III Study Assessing the Efficacy and Safety of Brolucizumab 6 mg Compared to Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 689
- 试验地点
- 41
- 主要终点
- Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 54 for the Study Eye
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of brolucizumab compared to panretinal photocoagulation laser (PRP) in patients with proliferative diabetic retinopathy (PDR). This evaluation will provide information that brolucizumab is non-inferior to PRP with respect to the change in best corrected visual acuity at Week 54.
详细描述
Phase III, 96-week, two-arm, randomized (1:1 ratio), single-masked, multi-center, active-controlled study to evaluate the efficacy and safety of brolucizumab compared to Panretinal photocoagulation (PRP) in subjects with Proliferative diabetic retinopathy (PDR).
Subjects who consented underwent screening assessments to evaluate their eligibility based on the inclusion and exclusion criteria. Subjects who met all the inclusion and none of the exclusion criteria were randomized in a 1:1 ratio to one of the following treatments:
Brolucizumab 6 mg: 3 x q6w loading then q12w maintenance through Week 90, with the option from Week 48 onwards to extend the treatment interval by 6 weeks at a time up to 24 weeks, and revert to q12w if disease worsens. More frequent injection with q6w interval in the maintenance phase could be administered at the discretion of the Investigator if the disease worsens.
PRP: initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment (may split into 2-4 sessions) as needed up to Week 90.
Visits occurred every 6 weeks throughout the study, regardless of treatment or not.
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)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation
- •Able to complete adequate fundus photographs and retinal images
- •Diagnosis of type 1 or 2 Diabetes Mellitus (DM) and HbA1c less than or equal to 12% at screening
- •DM treatment stable for at least 3 months
- •PDR diagnosis with no previous PRP treatment in the study eye
排除标准
- •Concomitant conditions or ocular disorders in the study eye at Screening or Baseline that could compromise a response to study treatment.
- •Presence of diabetic macular edema in the study eye
- •Active infection or inflammation in the study eye
- •Uncontrolled glaucoma (IOP greater than 25 mmHg)
- •Intravitreal anti-VEGF treatment within 6 months
- •Treatment with intraocular corticosteroids
- •End stage renal disease requiring dialysis or kidney transplant
- •Uncontrolled blood pressure
- •Systemic anti-VEGF therapy at any time
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Brolucizumab 6 mg
Intra-vitreal injection. 3 x q6w loading injections, followed by q12w maintenance through Week 90
干预措施: Brolucizumab 6 mg (Biological)
Panretinal photocoagulation laser Arm
Initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment as needed
干预措施: Panretinal photocoagulation laser (Procedure)
结局指标
主要结局
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 54 for the Study Eye
时间窗: Baseline, Week 54
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of \>= 34 ETDRS letters (Snellen equivalent 20/200) at Screening / Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.
次要结局
- Number and Percentage of Subjects With no Proliferative Diabetic Retinopathy (PDR) at Week 54 for the Study Eye(Week 54)
- Number and Percentage of Subjects With no Proliferative Diabetic Retinopathy (PDR) at Week 96 for the Study Eye(Week 96)
- Number and Percentage of Subjects With Center-involved Diabetic Macular Edema (CI- DME) up to Week 54 for the Study Eye(Up to Week 54)
- Number and Percentage of Subjects With Center-involved Diabetic Macular Edema (CI- DME) up to Week 96 for the Study Eye(Up to Week 96)
- Area Under the Curve in Change From Baseline in BCVA up to Week 54 and up to Week 96 - for the Study Eye(Baseline, up to Week 54 and up to Week 96)
- Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥2 Steps Improvement From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96(Baseline, Week 54 and Week 96)
- Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥2 Steps Worsening From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96(Baseline, Week 54 and Week 96)
- Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥3 Steps Improvement From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96(Baseline, Week 54 and Week 96)
- Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥3 Steps Worsening From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96(Baseline, Week 54 and Week 96)
- Number and Percentage of Subjects Developing Vision-threatening Complications Associated With Diabetic Retinopathy up to Week 54 and up to Week 96(up to Week 54 and up to Week 96)
- Ocular AEs (>= 2% in Any Treatment Arm) by Preferred Term for the Study Eye(Adverse events are reported from first dose of study treatment up to Week 90, plus approximately 6 weeks post-treatment, up to a maximum timeframe of approximately 96 weeks.)
- Non-ocular AEs (≥ 2% in Any Treatment Arm) by Preferred Term(Adverse events are reported from first dose of study treatment up to Week 90, plus approximately 6 weeks post-treatment, up to a maximum timeframe of approximately 96 weeks.)