An Open-Label Phase 2a Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies (DLB)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Evaluate the safety and tolerability 80 mg neflamapimod given twice daily in patients with dementia with Lewy bodies.
研究概览
简要总结
The purpose of this clinical study is to evaluate the safety and tolerability (side effects) and pharmacokinetics (drug levels in the body) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
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 is willing and able to provide written informed consent.
- •Probable DLB by consensus criteria (McKeith et al, 2017; McKeith et al, 2020).
- •MoCA score ≥18 OR CDR global score (CDR-GS) ≤ 1.0 during Screening.
- •If the patient is currently receiving cholinesterase inhibitor and/or memantine therapy, the patient must have received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of enrollment. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study. If the patient is not currently receiving such therapy, but received such therapy previously, that therapy must have been discontinued at least 3 months prior to enrollment.
- •Normal or corrected eyesight 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.
- •Received vaccination for SARS-CoV-19 unless medical contraindications prevent being vaccinated or has a history of natural infection.
- •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), Frontotemporal dementia (FTD), or Parkinson's disease (PD).
- •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.
- •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 Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
- •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.
- •If patient is taking blood thinners (e.g., warfarin), and has no known liver issues, INR >
- •Positive screen for human immunodeficiency virus, hepatitis B surface antigen (HbsAg), antibody (anti-HbS), hepatitis C virus (HCV) antibody or evidence of latent or active tuberculosis, active opportunistic or life-threatening infections.
- •Participated in a study of an investigational drug less than 6 weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
- •Receipt of a live vaccine, with the exception of influenza, within 4 weeks before starting study drug treatment.
- •History of previous neurosurgery to the brain within the past five years.
- •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.
- •If female, currently pregnant or breastfeeding.
研究组 & 干预措施
Neflamapimod, Open-label
Neflamapimod will be administered orally, with food, for 24 weeks in subjects with DLB. Subjects will receive 4 capsules per day (80 mg BID), two capsules in the morning and two capsules in the evening, with food (i.e., with the morning and evening meals)
干预措施: neflamapimod (Drug)
结局指标
主要结局
Evaluate the safety and tolerability 80 mg neflamapimod given twice daily in patients with dementia with Lewy bodies.
时间窗: From enrollment until the end of treatment at 24 weeks
The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of treatment-emergent Adverse events (AEs) and Serious adverse events (SAEs) during 24 weeks of treatment
Evaluate the safety and tolerability of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.
时间窗: From enrollment until the end of treatment at 24 weeks
The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of elevations in amino-alanine transferase (ALT) and/or aspartate amino-transferase (AST) ≥ three times the upper limit of normal during 24 weeks of treatment
Evaluate the maximum plasma concentration (Cmax) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.
时间窗: From enrollment until the end of treatment at 24 weeks
The maximum plasma concentration (Cmax) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.
Evaluate the trough plasma concentration (Ctrough) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.
时间窗: From enrollment until the end of treatment at 24 weeks
The trough plasma concentration (Ctrough) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.
次要结局
- Change in ADNI-EF composite score from baseline to 24 weeks(From enrollment until the end of treatment at 24 weeks)
- Change in CDR-SB score from baseline to 24 weeks(From enrollment until the end of treatment at 24 weeks)
- Change in TUG test results from baseline to 24 weeks(From enrollment until the end of treatment at 24 weeks)