A 64-week, Two-arm, Randomized, Double-masked, Multicenter, Phase IIIb Study Assessing the Efficacy and Safety of Brolucizumab 6 mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen in Patients With Neovascular Agerelated Macular Degeneration (TALON)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 734
- 试验地点
- 1
- 主要终点
- Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye
研究概览
简要总结
This was a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with neovascular age related macular degeneration (nAMD) who have not previously received anti- vascular endothelial growth factor (VEGF) treatment.
详细描述
At the baseline Visit, subjects who met the eligibility criteria were randomized in a 1:1 ratio to receive either: -Brolucizumab 6 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62
-Aflibercept 2 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to-Control treatment from Week 16 up to Week 60/62.
For all subjects, the last potential study treatment was at the Week 60 visit (or at the Week 62 visit for subjects whose actual treatment interval would require a treatment at Week 62). The initiation phase starts on Day 1 and ends on Week 16. Treat to Control regimen starts on Week 16 until end of treatment (Week 60/62).
In both treatment arms, treatment intervals after the initiation phase were either 8 weeks, 12 weeks, or 16 weeks. Per the original protocol, if it was determined that a patient required more frequent injections than q8w, he/she would be moved to a q4w treatment interval. However, this option was removed per Protocol amendment 02, after which, dosing intervals shorter than q8w were not permitted.
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
- 50 Years 至 —（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 in the study
- •Male or female patients ≥ 50 years of age at screening who are treatment naive
- •Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye)
- •Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye)
- •Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye)
排除标准
- •Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye)
- •Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye)
- •Uncontrolled glaucoma defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye)
- •Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye)
- •Stroke or myocardial infarction during the 6-month period prior to baseline
- •Systemic anti-VEGF therapy at any time.
研究组 & 干预措施
Brolucizumab 6 mg
3 x 4-week injections and one 8-week Intra-vitreal injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62.
干预措施: Brolucizumab 6 mg (Biological)
Aflibercept 2 mg
3 x 4-week injections and one 8-week Intra-vitreal injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62
干预措施: Aflibercept 2 mg (Biological)
结局指标
主要结局
Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye
时间窗: Baseline, Week 28 and Week 32
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined.
Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye
时间窗: Up to Week 32
No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used.
次要结局
- Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye(Up to Week 64)
- Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye(Baseline, Week 32, and Week 64)
- Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye(Baseline, Weeks 28 and 32 and at Weeks 60 and 64)
- Number of Participants With no Disease Activity - Study Eye(Weeks 14 and 16)
- Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye(Up to Week 64)
- Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye(Week 32 and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye(Baseline, Week 32, and Week 64)
- Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% 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 duration of 483 days, approx. 69 weeks, 1.3 years.)
- Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye(Up to Week 64)
- Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye(Up to Week 64)
- Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye(At Weeks 28, 32, 60 and 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye(Baseline, Week 32, and Week 64)
- Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table(Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.)
- Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye(Baseline, Week 60 and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye(Baseline, Week 32, and Week 64)
- Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye(At Weeks 28, 32, 60 and 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye(Baseline, Week 32, and Week 64)
- Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye(Baseline, Week 32, and Week 64)