A Phase 2b Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel Group Dose Finding, Safety, Tolerability and Efficacy Study of PQ912 in Subjects With MCI and Mild Dementia Due to Alzheimer's Disease.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 259
- 试验地点
- 17
- 主要终点
- Primary efficacy: within-participant linear change with time of the combinded z-score for cognition compared between active arm and placebo.
研究概览
简要总结
This is a phase 2B multicenter, randomized, double-blind, placebo-controlled, parallel group dose finding study to evaluate the safety, tolerability and efficacy of PQ912, an inhibitor of the glutaminyl cyclase enzyme, in 250 subjects with mild cognitive impairment and mild dementia due to Alzheimer 's Disease.
详细描述
In the parallel group dose finding part of the study the first 90 subjects will be randomized 1:1:1 between PQ912 300 mg BID, 600 mg BID, and placebo. When the 90th patient has completed the week 24 treatment visit, the DSMB will decide on the dose of PQ912 to be continued. The decision is based on safety findings only, no efficacy data will be considered. After the DSMB has reached a decision on the dose to be continued, all subjects randomized to receive PQ912 will be reallocated to this dose (1:1). The duration of Subjects participation in the study is either 48, 60, 72, 84 or 96 weeks of treatment (depending on time of randomization). Subjects recruited early into the study will be kept on treatment for 96 weeks or until the regular, scheduled study visit which is closest to the scheduled week 48 visit of the last subject recruited in the study, whichever comes first.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Positive CSF AD biomarker signature according to the AA-NIA criteria
- •Clinical syndrome of MCI or mild dementia according to the AA-NIA Research Framework
- •A cognitive impairment in the WAIS IV Coding Test of at least 0.5 standard deviation below the normative data
- •Adequate visual and auditory abilities to perform the cognitive and functional assessments in the opinion of the investigator
- •Meeting the completion and performance criteria for the CogState NTB
- •Outpatient with study partner capable of accompanying the subject on all applicable clinic visits
排除标准
- •Significant neurological or psychiatric disorders, other than AD, that may affect cognition.
- •Atypical clinical presentations of MCI due to AD or mild dementia due to AD, such as the visual variant of AD (including posterior cortical atrophy), frontal variant or the language variant (including logopenic aphasia).
- •Moderate and severe dementia with a Mini-Mental State Examination score (MMSE) below
- •Current presence of a clinically important major psychiatric disorder (e.g. major depressive disorder) as defined by DSM-5 criteria, or symptom(s) (e.g. hallucinations) that could affect the subject's ability to complete the study.
- •History of clinically evident stroke.
- •History of seizures within the last two years prior to the screening visit.
- •Myocardial infarction within the last six months prior to screening.
- •History of uncontrolled hypertension (in the opinion of the investigator) within six months prior to screening.
- •Contraindication to lumbar puncture and MRI
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
300 mg
Dose in weeks 1 and 2: 50 mg once daily (evening) Dose in weeks 3 and 4: 50 mg BID Dose in weeks 5-8: 150 mg BID Dose in weeks 9-24: 300 mg BID
干预措施: PQ912 (Drug)
600 mg
Dose in weeks 1 and 2: 50 mg once daily (evening) Dose in weeks 3 and 4: 50 mg BID Dose in weeks 5-8: 150 mg BID Dose in weeks 9-12: 300 mg BID Dose in weeks 12-24: 600 mg BID
干预措施: PQ912 (Drug)
结局指标
主要结局
Primary efficacy: within-participant linear change with time of the combinded z-score for cognition compared between active arm and placebo.
时间窗: 48 weeks and EoT (96 weeks at maximum)
The within-participant change over time in cognition measured by the combined z-score of the Detection test, Identification test and the 'One Back' test (attention and working memory domains) of the Neurological Test Battery
Primary safety: The proportion of participants who experience any Adverse Event (AE), Serious Adverse Event (SAE), Adverse Event of Interest (AE-I)
时间窗: 48 weeks
The safety analysis will include the number of subjects with, and the number of any AE, any SAE (both overall and related), AEs leading to discontinuation of treatment, AEs leading to temporary treatment interruption, treatment compliance, the number of subjects with AEs of interest as defined above, the severity, duration and outcome of AEs
次要结局
- Secondary efficacy: The within-participant linear change from baseline to week 48 in quantitative EEG (global relative theta wave power), compared between active and placebo.(48 weeks at minimum or until EoT (96 weeks at maximum))
- Secondary efficacy: The within-participant linear change with time in overall cognition as measured by the CogState Brief Battery (CBB) Z-score compared between active arm and placebo(48 weeks and EoT (96 weeks at maximum))