A Double-Blind, Placebo-Controlled 16-Week Study of the Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies (DLB)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 23
- 主要终点
- Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test
研究概览
简要总结
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1) administered with food for 16 weeks in subjects with DLB. The primary objective is to evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific Cogstate Neuropsychological Test Battery (NTB). Secondary endpoints include the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI-10), Timed Up and Go Test, and electroencephalogram (EEG) as a potential biomarker for DLB.
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
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged ≥55 years.
- •Subject or subject's legally authorized representative is willing and able to provide written informed consent.
- •Probable DLB and identified cognitive deficits, according to current consensus criteria (McKeith et al, 2017), specifically one core clinical feature and a positive DaTscan. If a negative DaTscan, but the subject has historical PSG-verified RBD, the subject would also qualify.
- •MMSE score of 15-28, inclusive, during Screening.
- •Currently receiving cholinesterase inhibitor therapy, having received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of randomization. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study.
- •Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
- •No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
- •Must have reliable informant or caregiver.
排除标准
- •Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB, including, but not limited to, post-stroke dementia, vascular dementia, Alzheimer's disease (AD), or Parkinson's disease (PD).
- •Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the C-SSRS, or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
- •Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
- •Diagnosis of alcohol or drug abuse within the previous 2 years.
- •Poorly controlled clinically significant medical illness, such as hypertension (blood pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would interfere with assessment of drug safety.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.
- •Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
- •Participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
- •History of previous neurosurgery to the brain.
- •If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
- •If female who has not has not reached menopause >1 year previously or has not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positive pregnancy test result during Screening and/or is unwilling or unable to adhere to the contraception requirements specified in the protocol.
研究组 & 干预措施
Neflamapimod
40 mg capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing <80 kg or the TID regimen if weighing ≥80 kg
干预措施: Neflamapimod (Drug)
Placebo
40 mg matching placebo capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing <80 kg or the TID regimen if weighing ≥80 kg
干预措施: Neflamapimod (Drug)
结局指标
主要结局
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test
时间窗: As the analysis was by Mixed Model for Repeated Measures, all time points at which NTB was assessed utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Change from Baseline to Week 4, Week 8, and Week 16 in the composite z-score of a study-specific Neuropsychological Test Battery (NTB) that included the following six tests: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test, and Category Fluency Test (CFT). Each score on the individual tests was converted to a z-score, and then a total z-score for the composite was calculated, in which each test is weighted equally. As the analysis is based on z-scores, there is no minimum or maximum value. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A positive change in z-score indicate an improvement in cognition, i.e., a better outcome; and a negative change in z-score indicates a worsening in cognition, i.e., a worse outcome.
次要结局
- International Shopping List Test (ISLT) - Immediate Recall(As the analysis was by Mixed Model for Repeated Measures, both time points at which ISLT was assessed (Weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.)
- Timed Up and Go Test (TUG)(As the analysis was by Mixed Model for Repeated Measures, both time points at which the TUG was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.)
- Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)(As the analysis was by Mixed Model for Repeated Measures, both time points at which CDR-SB was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.)
- Mini-Mental State Examination (MMSE)(As the analysis was by Mixed Model for Repeated Measures, both time points at which MMSE was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.)
- Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score(As the analysis was by Mixed Model for Repeated Measures, all time points at which NPI-10 was assessed (weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.)
- Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe(16 weeks)