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临床试验/NCT03622580
NCT03622580已完成3 期

A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients With Diabetic Macular Edema (YOSEMITE)

Hoffmann-La Roche184 个研究点 分布在 1 个国家目标入组 940 人开始时间: 2018年9月5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
940
试验地点
184
主要终点
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
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相关资讯

研究概览

简要总结

This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).

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

  • •Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
  • •Hemoglobin A1c (HbA1c) of less than or equal to (≤) 10% within 2 months prior to Day 1
  • •Macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea
  • •Decreased visual acuity attributable primarily to DME
  • •Ability and willingness to undertake all scheduled visits and assessments
  • •For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment

排除标准

  • •Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1
  • •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
  • •Treatment with panretinal photocoagulation or macular laser within 3 months prior to Day 1 to the study eye
  • •Any intraocular or periocular corticosteroid treatment within the past 6 months prior to Day 1 to the study eye
  • •Prior administration of IVT faricimab in either eye
  • •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

A: Faricimab 6 mg Q8W

Experimental

Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.

干预措施: Faricimab (Drug)

A: Faricimab 6 mg Q8W

Experimental

Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.

干预措施: Sham Procedure (Procedure)

B: Faricimab 6 mg PTI

Experimental

Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections once every 4 weeks (Q4W), 8 weeks (Q8W), 12 weeks (Q12W), or 16 weeks (Q16W) up to Week 96, followed by the final study visit at Week 100.

干预措施: Faricimab (Drug)

B: Faricimab 6 mg PTI

Experimental

Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections once every 4 weeks (Q4W), 8 weeks (Q8W), 12 weeks (Q12W), or 16 weeks (Q16W) up to Week 96, followed by the final study visit at Week 100.

干预措施: Sham Procedure (Procedure)

C: Aflibercept 2 mg Q8W

Active Comparator

Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.

干预措施: Aflibercept (Drug)

C: Aflibercept 2 mg Q8W

Active Comparator

Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.

干预措施: Sham Procedure (Procedure)

结局指标

主要结局

Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

时间窗: From Baseline through Week 56

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.

次要结局

  • Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations(Baseline and Week 52)
  • Change From Baseline in BCVA in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations(Baseline, average of Weeks 48, 52, and 56)
  • Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population(Baseline, Weeks 16, 52, and 96)
  • Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 16, 52, and 96)
  • Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population(Baseline, Weeks 16, 52, and 96)
  • Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 16, 52, and 96)
  • Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population(Baseline, Weeks 16, 52, and 96)
  • Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population(Week 96)
  • Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations(From start of PTI (Week 12 or later) until Week 52)
  • Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 16, 52, and 96)
  • Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations(Baseline and Week 52)
  • Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population(Week 52)
  • Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population(Week 52)
  • Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population(Week 96)
  • Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations(Baseline and Week 52)
  • Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations(From start of PTI (Week 12 or later) until Week 96)
  • Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations(From Baseline through Week 56)
  • Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population(Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100)
  • Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations(Average of Weeks 48, 52, and 56)
  • Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population(Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100)
  • Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population(Baseline, Weeks 24, 52, and 100)
  • Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100)
  • Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population(Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100)
  • Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye(From first dose of study drug through end of study (up to 2 years))
  • Percentage of Participants With at Least One Adverse Event(From first dose of study drug through end of study (up to 2 years))
  • Percentage of Participants With at Least One Non-Ocular Adverse Event(From first dose of study drug through end of study (up to 2 years))
  • Plasma Concentration of Faricimab Over Time(Pre-dose on Day 1 (Baseline); Weeks 4, 28, 52, 76, and 100)
  • Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study(Baseline, Weeks 4, 28, 52, 76, and 100)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (184)

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