A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,053
- 试验地点
- 172
- 主要终点
- DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
研究概览
简要总结
This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 116. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Gantenerumab
Gantenerumab will be administered as SC injections with gradual uptitration.
干预措施: Gantenerumab (Drug)
Placebo
Placebo will be administered as SC injections with gradual uptitration.
干预措施: Placebo (Drug)
结局指标
主要结局
DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
时间窗: Baseline, Week 116
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement.
China Extension: DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
时间窗: Baseline, Week 116
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement.
次要结局
- DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score(Baseline, Week 116)
- DBT Period: Number of Participants With at Least One Adverse Event (AE)(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score(Baseline, Week 116)
- DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Magnetic Resonance Imaging (MRI) Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) MRI Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With Injection-Site Reactions(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Total Tau (tTau)(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181)(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL)(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog13 Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in ADCS-ADL Total Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in FAQ Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in the Coding (DSST) Subtest(Baseline, Week 116)
- China - DBT Period: Number of Participants With at Least One AE(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: DBT Period: Change From Baseline to Week 116 in MMSE Total Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog11 Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in VFT Score(Baseline, Week 116)
- China - DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: Number of Participants With at Least One ARIA-E MRI Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: Number of Participants With at Least One ARIA-H MRI Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: Number of Participants With Injection-Site Reactions(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- OLE Period: Number of Participants With at Least One AEs(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))
- OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))
- OLE Period: Number of Participants With at Least One ARIA-H MRI Finding(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))
- OLE Period: Number of Participants With at Least One ARIA-E MRI Finding(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))