A Patient- and Investigator-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Study Participants With Prodromal to Mild Alzheimer's Disease (AD), Followed by an Open-Label Extension Period
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 466
- 试验地点
- 190
- 主要终点
- Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score
研究概览
简要总结
The purpose of the study is to investigate the effect of bepranemab versus (vs) placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) up to Week 80 in study participants with prodromal or mild Alzheimer's Disease (AD).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •50 to 80 years of age
- •Diagnosis of prodromal/mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD according to National Institute of Aging-Alzheimer's Association (NIA-AA)
- •A global Clinical Dementia Rating (CDR) score of 0.5 to 1.0 and CDR-Memory Box (CDRMB) score ≥0.5 at Screening and Baseline
- •Score of ≤85 for the delayed recall domain of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at Screening
- •Mini-Mental State Examination (MMSE) score ≥20 at Screening
- •Participant has an identified informant that has and will maintain sufficient contact (minimum of 5 hours per week) with the participant to be able to provide accurate information on the participant's cognitive, functional, and emotional states and of the participant's personal care
- •At least 6 years of formal education after the age of 5 or work experience to exclude mental deficits other than prodromal or mild AD dementia
- •Evidence of cerebral Aβ accumulation by either positive amyloid assessment by either positron emission tomography (PET) scan or cerebrospinal fluid pTau181/Aβ1-42 ratio assessment
排除标准
- •Any evidence of a condition that may affect cognition other than AD
- •Contraindications to PET imaging
- •Inability to tolerate or contraindication to magnetic resonance imaging
- •Any serious medical condition or abnormality that in the opinion of the investigator would preclude safe participation in and completion of the study or interfere with study assessments and/or study interpretation
- •Alcohol or drug abuse within 2 years of screening
- •Use of any experimental therapy within the past 6 months (or 5 half lives) prior to screening
- •Previous treatment with medication intended to treat a neurodegenerative disorder (other than AD) within 1 year of screening
- •Chronic daily treatment with atypical antipsychotics, opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally acting antihistamine or anticholinergic activitiy
- •Received treatment with monoclonal antibodies (mAbs), cytokines, immunoglobulins, or other blood products within 3 months or 5 half-lives (whichever is longer) prior to first dosing
研究组 & 干预措施
Dose level 1 bepranemab
Participants randomized to this arm will receive pre-specified doses (Dose level 1) of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period.
干预措施: Bepranemab (Biological)
Dose level 2 bepranemab
Participants randomized to this arm will receive pre-specified doses (Dose level 2) of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period.
干预措施: Bepranemab (Biological)
Placebo Arm
Participants randomized to this arm will receive Placebo to maintain the blinding during the Double-blind Treatment Period and will re-randomized during the Open-label Extension Period to receive pre-specified doses of bepranemab.
干预措施: Bepranemab (Biological)
Placebo Arm
Participants randomized to this arm will receive Placebo to maintain the blinding during the Double-blind Treatment Period and will re-randomized during the Open-label Extension Period to receive pre-specified doses of bepranemab.
干预措施: Placebo (Other)
结局指标
主要结局
Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score
时间窗: From from Baseline to Week 80
The Clinical Dementia Rating (CDR) scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None=0, Questionable=0.5, Mild=1, Moderate=2, and Severe=3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment.
次要结局
- Change from Baseline to Week 56 and Week 80 on indices of tau burden in the brain as measured by [18F]Genentech tau probe 1 (GTP1) positron emission tomography (PET)(From from Baseline to Week 56 and Week 80)
- Change from Baseline to Week 56 and Week 80 in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14)(From from Baseline to Week 56 and Week 80)
- Change from Baseline to Week 56 and Week 80 in Amsterdam-Instrumental Activities of Daily Living (A-iADL)(From from Baseline to Week 56 and Week 80)
- Incidence of treatment-emergent adverse events (TEAEs)(From Baseline to the Safety Follow-Up (Week 152))
- Incidence of treatment-emergent serious adverse events (TESAEs)(From Baseline to the Safety Follow-Up (Week 152))
- Change from Baseline to Week 56 and Week 80 in Mini-Mental State Examination (MMSE) total score(From from Baseline to Week 56 and Week 80)
- Incidence of TEAEs leading to discontinuation or death(From Baseline to the Safety Follow-Up (Week 152))
- Incidence of Drug-related TEAEs(From Baseline to the Safety Follow-Up (Week 152))
- Change from Baseline in suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)(From from Baseline to Week 80)
- Serum concentrations of bepranemab over the 80-week Double-blind Treatment Period(From from Baseline to Week 80)