A Phase 2a Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multi-center Study Investigating the Safety and Tolerability of JNJ-54861911 in Subjects With Early Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 114
- 主要终点
- Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 during 6 months of treatment in participants with early (predementia) alzheimer's disease (AD [degenerative disease of the brain characterized by the insidious onset of dementia, impairment of memory, judgment, attention span, and problem solving skills are followed by severe apraxias and a global loss of cognitive abilities]).
详细描述
This is a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), randomized (study drug assigned by chance), multi-center (when more than one hospital or medical school team work on a medical research study), parallel-group study. The study consists of 3 Parts; Screening Phase of 90 days, double-blind Treatment Phase of 6 months and Follow-up Phase of 7 to 28 days following the last dose in Month 6. Eligible participants in the early (predementia) AD spectrum will be randomized to either Treatment group 1, 2 or placebo and participants who previously participated in study 54861911ALZ1005 will be enrolled in this study and will receive the same treatment as in study 54861911ALZ1005. The study duration for each participant will be approximately 10 months. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study, including magnetic resonance imaging (MRI) and cognitive measures.
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, Care Provider)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants in the early alzheimer's disease (AD) spectrum must have a global Clinical Dementia Rating Scale( CDR) score of 0 (asymptomatic at risk for AD) to 0.5 prodromal AD (pAD) inclusive
- •Participants must have evidence of amyloid pathology by means of either: a) low Cerebrospinal Fluid (CSF) ABeta 1-42 levels at screening; b) a positive amyloid positron emission tomography (PET) scan at screening (depending on the site's PET capability) by visual read
- •Participants must have a body mass index between 18 and 35 kilogram per square meter (kg/m^2), inclusive, at screening
- •Participants must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening or at baseline. If there are abnormalities, they must be consistent with the underlying illness in the study population and not a potential cause of cognitive impairment, with written concurrence with the sponsor's medical monitor
- •Before randomization, a woman must be not of childbearing potential: postmenopausal (greater than or equal to [>=] 50 years of age with amenorrhea for at least 12 months; permanently sterilized [e.g., tubal occlusion, hysterectomy, bilateral salpingectomy]); or otherwise be incapable of pregnancy. In case of questionable status qualified personal of the sponsor should be consulted to decide on the potential for inclusion of the participant
排除标准
- •Participant has evidence of any brain disease, other than potential very early signs of AD (e.g. mild hippocampal atrophy) or typical age-related changes (e.g. mild white matter hyperintensity on magnetic resonance imaging [MRI]) or any other abnormality (e.g. folic acid/Vitamin B12 deficiency) that could explain a possible cognitive deficit (including, but not limited to vascular encephalopathy or strokes including lacuna's (as imaged by cerebral MRI) and Major Depression (as defined by most current Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria)
- •Participant has evidence of familial autosomal dominant AD. (Inclusion can be made upon written confirmation by sponsor, when the mutation is known and deemed not to be modulating Beta-secretase [BACE] cleavage)
- •Participant with history or presence of significant depression as defined by the most current DSM criteria
- •Participant has a clinically significant abnormal physical- or neurological examination, vital signs at screening or baseline (Day 1 predose)
- •Participant has a history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances (e.g. unstable situation needing monitoring or regular dose adaptations)
研究组 & 干预措施
Placebo
Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6.
干预措施: Placebo (Drug)
Treatment Group 1
Participants will self-administer JNJ-54861911, two tablets of 5 milligram (mg) each for a total of 10 mg, orally, once daily, from Day 1 until Month 6.
干预措施: JNJ-54861911, 10 milligram (mg) (Drug)
Treatment Group 2
Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6.
干预措施: JNJ-54861911, 50 mg (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: up to 10 months
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
次要结局
- Percent Change From Baseline in Plasma ABeta 1-40 Levels and sAPP Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels(Baseline and Month 6 (Day 168))
- Maximum Plasma Concentration (Cmax) of JNJ-54861911(Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168)
- Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels and Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels(Baseline and Month 6)
- Time to Reach the Maximum Plasma or CSF concentration (Tmax)(Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168)
- Relationship Between Dose and Exposure of JNJ-54861911 With Safety(Month 1 up to Month 6)
- Relationship Between Changes in CSF and Plasma ABeta Species and sAPP Fragments With Safety(Month 1 up to Month 6)
- Area Under the Plasma/CSF Concentration-time Curve From Time 0 to tau Hours Post Dosing (AUCtau)(Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168)