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临床试验/NCT04047472
NCT04047472已完成3 期

A Twelve-Month, Randomized, Double-Masked, Multicenter, Phase III, Two-Arm Study Comparing the Efficacy and Safety of Brolucizumab 6 mg Versus Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration

Novartis Pharmaceuticals1 个研究点 分布在 1 个国家目标入组 397 人开始时间: 2019年11月29日最近更新:
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试验速览

阶段
3 期
状态
已完成
入组人数
397
试验地点
1
主要终点
Change From Baseline at Week 48 in Best-Corrected Visual Acuity in Study Eye
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

To compare brolucizumab to aflibercept in Chinese patients with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD)

详细描述

This was a randomized, double-masked, multicenter, parallel-group, active-controlled study. The study included 14 scheduled visits over 48 weeks. After confirmation of eligibility at baseline, participants were randomized in a 1:1 ratio to one of the 2 treatment arms:

  • Brolucizumab 6 mg: 3 monthly intravitreal injections of brolucizumab 6 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 12 weeks (q12w regimen) or 8 weeks (q8w) up to Week 40 or Week 44, depending on disease activity status.
  • Aflibercept 2 mg: 3 monthly intravitreal injections of aflibercept 2 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 8 weeks (q8w) up to Week 40. Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Weeks 16, 20, 32 and 44 to determine the regimen of brolucizumab arm (i.e., q12w or q8w).

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
50 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Written informed consent must be obtained before any assessment was performed.
  • •Male or female Chinese participants ≥ 50 years of age at the time of screening.
  • •Active CNV lesions secondary to AMD that affect the central subfield (including retinal angiomatous proliferation lesions with a CNV component) in the study eye at screening and confirmed by the Central Reading Center (CRC).
  • •Total area of CNV (including both classic and occult components) must comprise > 50% of the total lesion area in the study eye at screening and confirmed by the CRC.
  • •Intra and/or subretinal fluid affecting the central subfield of the study eye at screening and confirmed by the CRC.
  • •BCVA between 78 and 23 letters, inclusive, in the study eye at screening and baseline using ETDRS testing.

排除标准

  • •Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at baseline.
  • •Central subfield of the study eye affected by fibrosis or geographic atrophy assessed by color fundus photography at screening and confirmed by the CRC.
  • •Total area of fibrosis ≥ 50% of the total lesion in the study eye at screening and confirmed by the CRC.
  • •Subretinal blood affecting the foveal center point and/or ≥ 50% of the lesion of the study eye at screening and confirmed by the CRC.
  • •Previous treatment with any approved or investigational drugs for nAMD in the study eye (other than vitamin supplements).
  • •Retinal pigment epithelium rip/tear in the study eye at screening.
  • •Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to baseline.

研究组 & 干预措施

Brolucizumab 6 mg

Experimental

3 monthly intravitreal injections of brolucizumab 6 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 12 weeks (q12w regimen) or 8 weeks (q8w) up to Week 40 or Week 44, depending on disease activity status.

干预措施: Brolucizumab 6mg (Drug)

Aflibercept 2 mg

Active Comparator

3 monthly intravitreal injections of aflibercept 2 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 8 weeks (q8w) up to Week 40.

干预措施: Aflibercept 2 mg (Drug)

结局指标

主要结局

Change From Baseline at Week 48 in Best-Corrected Visual Acuity in Study Eye

时间窗: Baseline, Week 48

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 between 78 and 23 ETDRS letters (inclusive) at Screening and 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

  • Average Change From Baseline Over the Period of Week 36 to Week 48 in Best-Corrected Visual Acuity in Study Eye(Baseline, over the period Week 36 to Week 48)
  • q12w Treatment Status at Week 48 (for Subjects Randomized to Brolucizumab 6 mg Only) - Probability(Week 44)
  • q12w Treatment Status at Week 48 Within the Subjects With no q8w Need During the First q12w Cycle (Week 16 and Week 20) (for Subjects Randomized to Brolucizumab 6 mg Only) - Probability(Week 44)
  • Number of Subjects With Best-Corrected Visual Acuity of 73 Letters or More at Each Visit(Baseline up to Week 48)
  • Number (%) of Participants With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit(Week 16)
  • Change From Baseline at Each Study Visit in Best-Corrected Visual Acuity in Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44)
  • Average Change From Baseline in Best Corrected Visual Acuity (Letters Read) From Week 4 or Week 12 up to Week 48 for the Study Eye(Baseline, over the period of Week 4 or Week 12 to Week 48)
  • Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 5, ≥ 10 and ≥ 15 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA ≥ 84 Letters at Week 48 for the Study Eye(Baseline up to Week 48)
  • Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 5 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA >=84 Letters at the Post-baseline Visit for the Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 10 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA >=84 Letters at the Post-baseline Visit for the Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 15 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA >=84 Letters at the Post-baseline Visit for the Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 5, ≥ 10 and ≥ 15 Letters in Best-correct Visual Acuity From Baseline at Week 48 for the Study Eye(Baseline, Week 48)
  • Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 15 Letters in Best-correct Visual Acuity From Baseline to Each Post-baseline Visit for the Study(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Average Change From Baseline Over the Period Week 4 Through Week 48 in Central Subfield Thickness - Total in Study Eye(Baseline, over the period Week 4 through Week 48)
  • Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 5 Letters in Best-correct Visual Acuity From Baseline to Each Post-baseline Visit for the Study(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 10 Letters in Best-correct Visual Acuity From Baseline to Each Post-baseline Visit for the Study(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Average Change From Baseline Over the Period Week 36 Through 48 in Central Subfield Thickness - Total in Study Eye(Baseline, over the period Week 36 to Week 48)
  • Change From Baseline at Each Study Visit in Central Subfield Thickness - Total in Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Change From Baseline at Each Study Visit in Central Subfield Thickness - Neurosensory Retina (μm) in Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Number of Participants With Presence of Subretinal Field (SRF) and/or Intraretinal Fluid (Central Subfield) (IRF) in the Study Eye at Each Postbaseline Visit (and Specifically Week 16 and Week 48)(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Number of Participants With Absence of Subretinal Field (SRF) and Intraretinal Fluid (Central Subfield) (IRF) in the Study Eye Between Week 36 and Week 48(Between Weeks 36 and Weeks 48)
  • Subretinal Fluid (SRF) Status in the Central Subfield: Number of Subjects With Presence of SRF by Visit for the Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Intraretinal Fluid (IRF) Status in the Central Subfield: Number of Subjects With Presence of IRF by Visit for the Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Subretinal Pigment Epithelium (Sub-RPE) Fluid Status in the Central Subfield: Number of Subjects With Presence of Sub-RPE by Visit for the Study Eye(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
  • Change From Baseline at Weeks 12 and 48 in Choroidal Neovascularization (CNV) Lesion in Study Eye(Baseline, Week 12 and Week 48)
  • Number of Subjects With Presence of Fibrosis (Central Subfield) in the Study Eye by Visit(Baseline, Week 12, Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Composite Score(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - General Vision(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Near Activities(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Mental Health(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Role Difficulties(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Dependency(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Driving(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Color Vision(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision(Baseline, Week 24 and Week 48)
  • Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating(Baseline, Week 24 and Week 48)
  • Anti-drug Antibody (ADA): Frequency Distribution of Pre-dose ADA Status in the Brolucizumab Arm(Baseline)
  • Anti-drug Antibody (ADA): Frequency Distribution of Integrated ADA Status in the Brolucizumab Arm(Baseline up to Week 48 (End of Study))
  • Pharmacokinetic Parameters: Cmax After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Pharmacokinetic Parameters: Tmax After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Pharmacokinetic Parameters: AUClast After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Pharmacokinetic Parameters: AUCinf After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Pharmacokinetic Parameters: T1/2 After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Pharmacokinetic Parameters: CL/F After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Pharmacokinetic Parameters: Vz/F After First Brolucizumab 6 mg Dose in a Subset of Subjects(Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29)
  • Most Common Ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term for the Study Eye(Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 48 weeks)
  • Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm)(Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 48 weeks)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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