A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ABBV-1758 in Participants With Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 210
- 试验地点
- 13
- 主要终点
- Percentage of Participants Experiencing Adverse Events (AEs)
研究概览
简要总结
Alzheimer's disease (AD) is a progressive, irreversible neurological disorder and is the most common cause of dementia in the elderly population. Clinical symptoms of the disease may begin with occasional forgetfulness such as misplacement of items, forgetting important dates or events, and may progress to noticeable memory loss, increased confusion and agitation, and eventually, loss of independence and non-responsiveness. The purpose of this study is to test how safe ABBV-1758 is, how well it works, how the body processes it and what effects it has on the body.
ABBV-1758 is an investigational drug being developed for the treatment of Alzheimer's disease. This study is conducted in 3 stages. Stage A is a multiple ascending dose study with a 1 in 5 chance (4:1 randomization) that participants are assigned to receive placebo. Stage B is a dose expansion phase, also using 4:1 randomization for ABBV-1758 or placebo. Stage C enrolls Japanese and Chinese participants with the same randomization scheme. Approximately 210 participants will be enrolled at about 55 sites in the United States, China, and Japan.
Participants will receive intravenous (IV) or subcutaneous (SC) doses of ABBV-1758 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for additional 12 weeks in the Follow-up Period. Participants will have the option of participating in a 12-month, blinded Extension Period receiving ABBV-1758 or placebo based on amyloid PET results.
There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The safety of the treatment will be checked by medical assessments, blood tests, and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Participants meeting all the following criteria for Alzheimer's disease (AD):
- •In regions where timely testing is feasible (e.g., results available within 4 weeks of Visit 1), plasma biomarker that is predictive of elevated brain amyloid at Screening for participants that do not have known elevated brain amyloid based on previous amyloid positron emission tomography (PET) results.
- •Participants with amyloid positron emission tomography PET scan results consistent with significant amyloid pathology (as determined by a Centiloid value of 50 or higher).
- •Participants must have a Mini-Mental State Examination (MMSE) score of 20 or higher at Screening.
排除标准
- •Participants with screening magnetic resonance imaging (MRI) that show evidence of another potential etiology for progressive dementia.
- •Participants who have any current serious conditions or illnesses that are not adequately controlled, or any conditions that, in the investigator's opinion, could interfere with the analyses in this study, including but not limited to psychiatric, neurologic (other than AD), cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, immunologic, or hematologic, metabolic, pulmonary, ophthalmologic, dermatologic, and/or any history of abnormal laboratory results that are indicative of significant disease(s).
- •Participants who had prior exposure to ABBV-1758 or any history of exposure to anti-amyloid beta monoclonal antibody (mAb) treatment.
- •Participants with other significant pathological findings on brain MRI at screening, including but not limited to:
- •Evidence of vasogenic edema
- •4 or more microhemorrhages (defined as 10 mm or less at the greatest diameter)
- •Any macrohemorrhage (defined as greater than 10 mm at the greatest diameter)
- •Any superficial siderosis
- •Severe white matter disease
研究组 & 干预措施
Placebo for ABBV-1758 - Expanded Cohort 1
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Placebo for ABBV-1758- Expanded Cohort 2
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Stage B- ABBV-1758 - Expanded Cohort 1
Participants will receive ABBV-1758 dose determined in Stage A Q4W.
干预措施: ABBV-1758 (Drug)
Stage B- ABBV-1758- Expanded Cohort 2
Participants will receive ABBV-1758 dose determined in Stage A Q4W.
干预措施: ABBV-1758 (Drug)
Placebo for ABBV-1758 Dose A
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Stage C- ABBV-1758- Japanese Cohort 2
Participants will receive ABBV-1758 dose determined in Stage A Q4W.
干预措施: ABBV-1758 (Drug)
Stage A-ABBV-1758 Dose D
Participants will receive ABBV-1758 dose D Q4W.
干预措施: ABBV-1758 (Drug)
Placebo for ABBV-1758- Japanese Cohort 2
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Placebo for ABBV-1758- Chinese Cohort
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Placebo for ABBV-1758 Dose B
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Placebo for ABBV-1758 Dose C
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Placebo for ABBV-1758 Dose D
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Placebo for ABBV-1758 - Japanese Cohort 1
Participants will receive Placebo for ABBV-1758.
干预措施: Placebo for ABBV-1758 (Drug)
Stage C- ABBV-1758 - Japanese Cohort 1
Participants will receive ABBV-1758 dose determined in Stage A Q4W.
干预措施: ABBV-1758 (Drug)
Stage A-ABBV-1758 Dose C
Participants will receive ABBV-1758 dose C Q4W.
干预措施: ABBV-1758 (Drug)
Stage A-ABBV-1758 Dose A
Participants will receive ABBV-1758 dose A once every 4 weeks (Q4W).
干预措施: ABBV-1758 (Drug)
Stage A-ABBV-1758 Dose B
Participants will receive ABBV-1758 dose B Q4W.
干预措施: ABBV-1758 (Drug)
Stage C- ABBV-1758-Chinese Cohort
Participants will receive ABBV-1758 dose determined in Stage A Q4W.
干预措施: ABBV-1758 (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Adverse Events (AEs)
时间窗: Up to approximately 40 weeks
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
Percentage of Participants with Abnormal Change from Baseline in Clinical Laboratory Test Results
时间窗: Up to approximately 40 weeks
Number of participants with abnormal change in clinical laboratory test results like hematology will be assessed.
Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA)
时间窗: Up to approximately 40 weeks
Amyloid related imaging abnormalities represent a spectrum of magnetic resonance imaging findings primarily observed in participants undergoing treatment with anti-amyloid therapies.
Percentage of Participants with Abnormal Change From Baseline in Vital Sign Measurements
时间窗: Up to approximately 40 weeks
Number of participants with abnormal change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed.
Percentage of Participants with Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters
时间窗: Up to approximately 40 weeks
12-lead resting ECGs will be recorded. Parameters include heart rate, PR interval, QT interval, QRS duration, and QT interval corrected using Fridericia's formula (QTcF).
Percentage of Participants Experiencing Any Suicidal Ideation or Suicidal Behavior As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to approximately 40 weeks
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.
Stage A, B, and C: Change from Baseline in Brain Amyloid Load
时间窗: Up to approximately 28 Weeks
Measured by amyloid positron emission tomography (PET)
Stage A and C: Maximum Plasma Concentration (Cmax) of ABBV-1758
时间窗: Up to approximately 40 weeks
Cmax of ABBV-1758
Stage A and C: Time to Cmax (Tmax) of ABBV-1758
时间窗: Up to approximately 40 weeks
Tmax of ABBV-1758
Stage A and C: Trough Concentration measured at the end of a dosing interval at steady state (Ctrough) of ABBV-1758
时间窗: Up to approximately 40 weeks
Ctrough of ABBV-1758
Stage A and C: Area under the Plasma Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of ABBV-1758
时间窗: Up to approximately 40 weeks
AUCtau of ABBV-1758
Stage A and C: Average Serum Concentration at Steady-State (Cav,ss) of ABBV-1758
时间窗: Up to approximately 40 weeks
Cav,ss of ABBV-1758
Stage A and C: Accumulation ratio for (AUCtau) of ABBV-1758
时间窗: Up to approximately 40 weeks
AUCtau of ABBV-1758
Stage A and C: Total Body Clearance (CL) of ABBV-1758
时间窗: Up to approximately 40 weeks
CL of ABBV-1758
Stage A and C: Apparent Clearance (CL/F) of ABBV-1758
时间窗: Up to approximately 40 weeks
CL/F of ABBV-1758
Stage A and C: Volume of Distribution at Steady-State (Vss)
时间窗: Up to approximately 40 weeks
Vss of ABBV-1758
Stage A and C: Apparent Volume of Distribution during the Terminal Phase (Vz)
时间窗: Up to approximately 40 weeks
Vz of ABBV-1758
Stage A and C: Terminal Phase Elimination Rate Constant (β) of ABBV-1758
时间窗: Up to approximately 40 weeks
β of ABBV-1758
Stage A and C: Terminal Phase Elimination Half-Life (t1/2) of ABBV-1758
时间窗: Up to approximately 40 weeks
Terminal phase elimination half-life of ABBV-1758
Stage A and C: Effective Half-Life (T1/2,eff)
时间窗: Up to approximately 40 weeks
T1/2,eff of ABBV-1758
次要结局
未报告次要终点