NCT05256134终止3 期
A Phase III, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 63
- 主要终点
- Change From Baseline in PACC-5 Score
研究概览
简要总结
A study to evaluate the efficacy and safety of gantenerumab in amyloid-positive, cognitively unimpaired participants at risk for or at the earliest stages of AD. The planned number of participants for this study is approximately 1200 participants randomized in a 1:1 ratio to receive either gantenerumab or placebo (600 participants randomized to gantenerumab and 600 participants randomized to placebo).
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
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to comply with the study protocol and complete all aspects of the study [including cognitive and functional assessments, physical and neurological examinations, MRI, CSF collection, genotyping, and positron emission tomography (PET) imaging].
- •Cognitively unimpaired with a screening clinical dementia rating global score (CDR-GS) of 0, and Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) >=
- •Evidence of cerebral amyloid accumulation.
- •Participants who have an available person (referred to as a "study partner").
- •Fluent in the language of the tests used at the study site.
- •Adequate visual and auditory acuity, sufficient to perform neuropsychological testing (eye glasses and hearing aids are permitted).
- •Agreed not to participate in other interventional research studies for the duration of this trial.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 17 weeks after the final dose of study treatment.
排除标准
- •Any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD.
- •Clinical diagnosis of mild cognitive impairment (MCI), prodromal AD, or any form of dementia.
- •History or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage.
- •History or presence of posterior reversible encephalopathy syndrome.
- •History of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack within 12 months of screening.
- •History of severe, clinically significant (i.e., resulting in persistent neurologic deficit or structural brain damage) central nervous system (CNS) trauma (e.g., cerebral contusion).
- •History or presence of intracranial mass lesion (e.g., glioma, meningioma) that could potentially impair cognition or lead to progressive neurological deficits.
- •Infections that may affect brain function or a history of infections that resulted in neurologic sequelae [e.g., human immunodeficiency virus (HIV), syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis].
- •History of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder.
- •At risk for suicide.
- •History of alcohol and/or substance abuse or dependence.
- •History or presence of clinically significant systemic vascular disease, atrial fibrillation or heart failure.
- •Within the last year, experienced unstable or clinically significant cardiovascular disease (e.g., myocardial infarction).
- •Uncontrolled hypertension.
- •Chronic kidney disease, indicated by creatinine clearance <30 mL/min.
- •Confirmed and unexplained impaired hepatic function.
- •History of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection that has not been adequately treated.
- •History or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits.
- •Systemic immunosuppression or immunomodulation due to the continuing effects of immunosuppressant or immunomodulating medications.
- •Current COVID-19 infection.
- •Evidence of folic acid or vitamin B-12 deficiency.
- •Any passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline within 1 year of screening.
- •Any other investigational treatment within 5 half-lives or 6 months (whichever is longer) prior to screening.
- •Typical/Atypical anti-psychotic medications or neuroleptic medications.
- •Anticoagulation medications within 3 months of screening with no plans to initiate any prior to randomization.
- •Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists are exclusionary at screening.
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the final dose of gantenerumab.
- •Impaired coagulation.
- •Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, including gantenerumab and gantenerumab excipients.
- •Participants who reside in a skilled nursing facility such as a convalescent home or long-term care facility.
- •Participants who require residence in such facilities during the study may continue in the study and be followed for efficacy and safety, provided that they have a study partner who meets the study partner requirements.
研究组 & 干预措施
Gantenerumab
Experimental
Gantenerumab will be administered as subcutaneous (SC) injection with gradual uptitration.
干预措施: Gantenerumab (Drug)
Placebo
Placebo Comparator
Placebo will be administered as SC injection with gradual uptitration.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in PACC-5 Score
时间窗: Baseline to early termination visit (up to 225 days from start of treatment)
The PACC-5 is computed as the average of z-scores of the following cognitive measures: 1. Wechsler Memory Scale (WMS LM I-II) - Total Score LM II Delayed Recall; 2. Free \& Cued Selective Reminding Test (FCSRT) -Immediate and Delayed Recall - Trials 1-3: Total Recall; 3. Wechsler Adult Intelligence Scale (WAIS) - IV Coding - Total Raw Score; 4. Mini Mental State Examination (MMSE) - Total Score; 5. Category Fluency Test (CFT) - 3 categories - Vegetables, Fruits and Animals - Total Admissible Words. The z-score was defined as the difference between the assessment and the mean of baseline assessments, divided by the standard deviation of baseline assessments. Z-scores range from -3 to +3 with higher scores indicating better cognitive performance.
次要结局
- Time to Onset of Confirmed Clinical Progression(Randomization to early termination Visit (up to 225 days from start of treatment))
- Change From Baseline in the Cognitive Function Instrument Acute (CFIa) Participant Version(Baseline to early termination visit (up to 225 days from start of treatment))
- Number of Participants With Post-baseline Suicidal Behaviors and Ideations as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Day 1 to safety follow-up visit (up to 310 days from start of treatment))
- Change From Baseline in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV)(Baseline to early termination visit (up to 225 days from start of treatment))
- Number of Participants With Injection-site Reactions (ISRs)(Day 1 to safety follow-up visit (up to 310 days from start of treatment))
- Time From Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia Due to AD(Randomization to early termination Visit (up to 225 days from start of treatment))
- Change From Baseline in the CFIa Study Partner Version(Baseline to early termination visit (up to 225 days from start of treatment))
- Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)(Baseline to early termination visit (up to 225 days from start of treatment))
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)(Day 1 to safety follow-up visit (up to 310 days from start of treatment))
- Number of Participants With Anti-Drug Antibodies (ADAs) to Gantenerumab(Day 1 to early termination visit (up to 216 days from start of treatment))
- Number of Participants With Magnetic Resonance Imaging (MRI) Findings: Amyloid-related Imaging Abnormalities - Edema/Effusion (ARIA-E) and ARIA-Hemosiderin Deposition (ARIA-H)(Day 1 to early termination visit (up to 248 days from start of treatment))
- Change in Brain Amyloid Load Over Time as Measured by Amyloid Positron Emission Tomography (PET) in a Subset of Participants(Baseline)
- Change in Brain Tau Load Over Time as Measured by Tau PET in a Subset of Participants(Baseline)
- Change in Cerebrospinal Fluid (CSF) Amyloid (A) Peptide Beta (β): Aβ 1-42 Over Time in a Subset of Participants(Baseline)
- Change in CSF Amyloid Peptide: Aβ 1-40 Over Time in a Subset of Participants(Baseline)
- Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants(Baseline)
- Change in Total Ventricular Volume Over Time as Determined by MRI in a Subset of Participants(Baseline)
- Change in CSF Neurofilament Light (NFL) Over Time in a Subset of Participants(Baseline)
- Change in CSF Total Tau (tTau) Over Time in a Subset of Participants(Baseline)
- Change in Whole Brain Volume Over Time as Determined by MRI in a Subset of Participants(Baseline)
- Change in Hippocampal Volume Over Time as Determined by MRI in a Subset of Participants(Baseline)
研究者
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