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
- 975
- 试验地点
- 155
- 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.
OLE Period: Number of Participants With Adverse Events (AEs)
时间窗: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.
OLE Period : Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI
时间窗: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD.
OLE Period: Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
时间窗: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces.
OLE Period: Number of Participants With Injection-Site Reactions
时间窗: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.
次要结局
- DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score(Baseline, Week 116)
- DBT Period: Number of Participants With ARIA-H Confirmed by MRI(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 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 128 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 128 weeks))
- 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 128 weeks))
- DBT Period: Number of Participants With ARIA-E Confirmed by MRI(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks))
- 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 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: 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 AEs(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks))
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin(Baseline, Week 116)
- 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 - 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 - 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)