A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 159
- 试验地点
- 71
- 主要终点
- Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients.
研究概览
简要总结
The purpose of this study is to determine whether neflamapimod can improve learning skills, problem solving skills, and memory loss in people diagnosed with DLB. More specifically, improvement in verbal learning, memory, and attention, as well as cognitive and functional performance will be measured.
详细描述
This study includes a 16-week blinded treatment period (randomized 1:1 neflamapimod:placebo) and a 32 week open-label extension during which all participants receive neflamapimod.
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)
盲法说明
Double-blind
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.
- •3. Probable DLB by consensus criteria (McKeith et al, 2017), including a positive DaTscan™. Specifically, the subject must have the presence of dementia in association with:
- •At least two (2) core clinical features (fluctuating cognition, visual hallucinations, REM sleep disorder, and/or parkinsonism); or
- •One (1) core clinical feature plus an abnormal DaTscan™. Historical polysomnography (PSG)-verified REM sleep behavioral disorder (RBD), FDG-PET imaging, or MIBG myocardial scintigraphy can take the place of an abnormal DaTscan™ in a patient with only one core clinical feature.
- •CDR Global Score 0.5 (very mild dementia) or 1.0 (mild dementia) during Screening
- •Background dementia therapy:
- •Not currently receiving cholinesterase inhibitor therapy. If the patient received such therapy previously, that therapy must have been discontinued at least 3 months prior to randomization.
- •Receiving cholinesterase inhibitor therapy alone. If the patient is currently receiving cholinesterase inhibitor 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 randomization. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study.
- •Memantine therapy is allowed, if it had been started at least 3 months prior to randomization and the patient is also receiving cholinesterase inhibitor therapy. If the patient has never been on cholinesterase inhibitor therapy (naïve), then memantine monotherapy is allowed.
- •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), or Parkinson's disease (PD).
- •Plasma ptau181 result above the threshold that indicates evidence of pathology associated with Alzheimer's disease at Screening.
- •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.
- •If patient is taking blood thinners (e.g., warfarin), and has no known liver issues, INR >
- •Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
- •Participated in a study of an investigational drug less than six weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
- •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.
- •Weight less than 50kg.
- •All participants who complete the initial 16-week period of the study will be able to continue in the study and receive neflamapimod for an additional 32 weeks (8 months) regardless of whether they received neflamapimod of placebo during the the first 16 weeks.
研究组 & 干预措施
Placebo
Placebo will be administered with food for 16 weeks in participants with DLB. Participants will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).
干预措施: Placebo (Drug)
Neflamapimod
Neflamapimod will be administered with food for 16 weeks in participants with DLB. Participants will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).
干预措施: Neflamapimod (Drug)
Open-label extension
Neflamapimod will be administered with food for 32 weeks in participants with DLB who have completed the blinded treatment period. Participants will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).
干预措施: Neflamapimod (Drug)
结局指标
主要结局
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients.
时间窗: 16 weeks
The primary objective is to demonstrate the efficacy of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the CDR-SB scale. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)
时间窗: 16 weeks
The primary objective is to demonstrate the efficacy of neflamapimod, in recipients of Drug Batch A compared to Drug Batch B, as a treatment for DLB, as assessed by the CDR-SB scale. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)
时间窗: 16 weeks
Evaluate the efficacy of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the CDR-SB scale. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.
次要结局
- Change in the composite score of the Neuropsychological Test Battery (NTB), including tests of attention, executive function, and visual learning in neflamapimod-treated subjects compared to placebo recipients.(16 weeks)
- Change in Timed Up and Go Test (TUG) in neflamapimod-treated subjects compared to placebo recipients.(16 weeks)
- Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) score at Week 16 in neflamapimod-treated subjects compared to placebo recipients.(16 weeks)
- Change in Timed Up and Go Test (TUG) in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)(16 weeks)
- Change in the Composite Score of the Neuropsychological Test Battery (NTB), Including Tests of Attention, Executive Function, and Visual Learning in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)(16 weeks)
- Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) Score at Week 16 in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)(16 weeks)
- Change in Timed Up and Go Test (TUG) in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)(16 weeks)
- Change in the Composite Score of the Neuropsychological Test Battery (NTB), Including Tests of Attention, Executive Function, and Visual Learning in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)(16 weeks)
- Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) Score at Week 16 in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)(16 weeks)