A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of ABBV-916 in Subjects With Early Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 106
- 试验地点
- 32
- 主要终点
- Stage A: Area Under the Concentration-Time Curve (AUC) of ABBV-916
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. This study will assess how safe and effective ABBV-916 is in treating early AD. Adverse events, change in disease activity, and how ABBV-916 moves through body of participants will be assessed.
ABBV-916 is an investigational drug being developed for the treatment of early AD. This study is conducted in 2 stages. Stage A is a multiple ascending dose study. There is a 1 in 4 chance that participants are assigned to receive placebo. Stage B is a proof-of-concept study. In Stage B, there is a 1 in 5 chance that participants will be assigned to receive placebo. The first 6 months of this study are "double-blind," which means that neither the trial participant nor the study doctors know which treatments will be given. This will be followed by a 2-year extension period in which all participants will receive ABBV-916. Approximately 195 participants aged 50-90 years will be enrolled in about 90 sites across the world.
Participants will receive intravenous (IV) doses of ABBV-916 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for an additional 16 weeks. Participants will have the option of participating in a 2-year, open-label, Extension Period receiving IV ABBV-916.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, magnetic resonance imaging (MRI), blood tests, checking for side effects 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
- Quadruple (Participant, Care Provider, 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
- •Diagnosis of Stage 3 or Stage 4 Alzheimer's disease (AD) based on the 2018 National Institute on Aging (NIA)-Alzheimer's Association (AA) Research Framework Criteria.
- •Mini-Mental State Examination (MMSE) score of 20 to 28, inclusive, at Screening.
- •Blood-based biomarker results with a value consistent with amyloid positron emission tomography (PET) positivity. The biomarker will be chosen by the sponsor and described in the Laboratory Manual. Biomarker results will not be required for eligibility if the participant has a positive Amyloid PET scan meeting the central reader criteria.
- •Amyloid PET scan results consistent with amyloid pathology.
- •Stage B: Participants must have a study partner who spends a minimum average of 10 hours per week with the participant.
排除标准
- •Significant pathological findings on brain MRI at screening including, but not limited to, evidence of vasogenic edema, 4 or more microhemorrhages, any macrohemorrhages, any superficial siderosis, or severe white matter disease.
- •Any anticoagulants or have a bleeding disorder that is not adequately controlled.
研究组 & 干预措施
Stage A: ABBV-916
Participants will receive ABBV-916 for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
干预措施: ABBV-916 (Drug)
Stage A: Placebo for ABBV-916
Participants will receive Placebo for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
干预措施: Placebo (Drug)
Stage B: ABBV-916 Dose A
Participants will receive ABBV-916 Dose A for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
干预措施: ABBV-916 (Drug)
Stage B: Placebo for ABBV-916
Participants will receive Placebo for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
干预措施: Placebo (Drug)
Stage B: ABBV-916 Dose B
Participants will receive ABBV-916 Dose B for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
干预措施: ABBV-916 (Drug)
结局指标
主要结局
Stage A: Area Under the Concentration-Time Curve (AUC) of ABBV-916
时间窗: Up to approximately 24 weeks
AUC of ABBV-916 will be determined.
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Up to approximately 160 weeks
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.
Stage A: Terminal Phase Elimination Half-Life (t1/2) of ABBV-916
时间窗: Up to approximately 24 weeks
T1/2 of ABBV-916 will be determined.
Stage A: Maximum Observed Serum Concentration (Cmax) for Multiple Ascending Dose of ABBV-916
时间窗: Up to approximately 24 weeks
Cmax of ABBV-916 will be determined.
Stage A: Time to Cmax (Tmax) for Multiple Ascending Dose of ABBV-916
时间窗: Up to approximately 24 weeks
Tmax of ABBV-916 will be determined.
Stage A: Apparent Terminal Phase Elimination Rate Constant (β) of ABBV-916
时间窗: Up to approximately 24 weeks
Apparent terminal phase elimination rate constant (β) of ABBV-916 will be determined.
Stage A: Cerebrospinal Fluid (CSF) Concentration as a Measure of ABBV-916 Crossing the Blood Brain Barrier
时间窗: Up to approximately 24 weeks
The central value for ratio of ABBV-916 concentration in cerebrospinal fluid (CSF) to that in serum will be estimated for evaluation of the fraction of ABBV-916 crossing the blood brain barrier.
Stage A: Percentage of Participants With Antidrug Antibodies (ADA) as a Measure of Immunogenicity Following Multiple Ascending Dose of ABBV-916
时间窗: Up to approximately 24 weeks
Antidrug antibody (ADA) classification and titers for positive ADA samples will be determined.
Stage A: Trough Serum Concentration (Ctrough) of ABBV-916 at the End of a Dosing Interval
时间窗: Up to approximately 24 weeks
Ctrough of ABBV-916 will be determined.
Stage B: Change in Brain Amyloid Plaque Deposition (Amyloid Centiloid Value)
时间窗: Baseline (Week 0) through Week 24
Change from baseline in brain amyloid plaque deposition (amyloid centiloid value) is measured by amyloid positron emission tomography (PET) scan.
次要结局
未报告次要终点