A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multiple Dose, Biomarker and Safety Study of PTI-125 in Mild-to-moderate Alzheimer's Disease Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 5
- 主要终点
- Change From Baseline in CSF Abeta42
研究概览
简要总结
This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of PTI-125 in mild-to-moderate Alzheimer's disease patients.
详细描述
This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of PTI-125 in mild-to-moderate Alzheimer's disease patients. A total of sixty (60) patients will be enrolled in the study. Patients will receive Placebo, 50 mg or 100 mg b.i.d. of PTI-125. The objective of this study are to investigate the safety, and biomarkers of PTI-125 following 28-day repeat oral administration.
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
The sponsor, participant, care provider, investigator including sub-investigators and outcomes assessors will be blinded to throughout the study which includes using an Integrated Web Response System (IWRS) and electronic data capture (EDC) to ensure blinding during the study.
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
- •Ages >= 50 and <= 85 years
- •Informed consent form (ICF) signed by the subject or legally acceptable representative.
- •Clinical diagnosis of dementia due to possible or probable Alzheimer's disease
- •Mini-Mental State Examination score >= 16 and <= 26 at screening
- •If female, postmenopausal for at least 1 year
- •Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-h) nursing care
- •General health status acceptable for participation in the study
- •Fluency (oral and written) in English or Spanish
- •If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months. If receiving donepezil, any dose lower than 23 mg once daily.
- •The patient is a non-smoker for at least 3 years.
- •The patient or legal representative must agree to comply with the drawing of blood samples and with a lumbar puncture and the drawing of cerebrospinal fluid samples.
- •The patient has a ratio of total tau/Aβ42 in cerebrospinal fluid >= 0.
- •Patient has a caregiver or legal representative responsible for administering the drug and recording the time.
排除标准
- •Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
- •Enrollment in the previous PTI-125 trial
- •A medical condition that would interfere with a lumbar puncture
- •Residence in a skilled nursing facility and requiring 24 h care.
- •Clinically significant laboratory test results
- •Clinically significant untreated hypothyroidism
- •Insufficiently controlled diabetes mellitus
- •Renal insufficiency (serum creatinine > ULN)
- •Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)
- •History of ischemic colitis or ischemic enterocolitis
- •Unstable medical condition that is clinically significant in the judgment of the investigator
- •Alanine transaminase (ALT) or aspartate transaminase (AST) > ULN or total bilirubin > ULN.
- •History of myocardial infarction or unstable angina within 6 months before screening
- •History of more than 1 myocardial infarction within 5 years before screening
- •Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
- •Symptomatic hypotension, or uncontrolled hypertension
- •Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT interval value >= 450 msec for males or >= 470 msec for females.
- •Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
- •History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
- •Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
- •Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
- •Specific degenerative Central Nervous System disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
- •Wernicke's encephalopathy
- •Active acute or chronic Central Nervous System infection
- •Donepezil 23 mg quaque die currently or within 3 months prior to randomization
- •Discontinued AChEI < 30 days prior to randomization
- •Antipsychotics; low doses are allowed only if the subject has received a stable dose for at least 3 months before randomization
- •Tricyclic antidepressants and monoamine oxidase inhibitors
- •Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed
- •Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)
- •Antiepileptic medications if taken for control of seizures
- •Chronic intake of opioid-containing analgesics
- •Sedating H1 antihistamines
- •Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
- •Clinically significant illness within 30 days of enrollment
- •History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
- •Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus HCV antibody test at screening
- •Positive HIV test at screening
- •Positive urine drug test at screening
- •Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
- •Suicidality on C-SSRS at screening
研究组 & 干预措施
Placebo Cohort
Subjects administered placebo oral tablets twice daily (BID)
干预措施: Placebo oral tablet (Drug)
Simufilam (PTI-125) 100 mg tablets Cohort
Subjects administered simufilam (PTI-125) 100 mg oral tablets twice daily (BID)
干预措施: Simufilam 50 mg oral tablet (Drug)
Simufilam (PTI-125) 50 mg tablets Cohort
Subjects administered simufilam (PTI-125) 50 mg oral tablets twice daily (BID)
干预措施: Simufilam 100 mg tablet (Drug)
结局指标
主要结局
Change From Baseline in CSF Abeta42
时间窗: Screening to Day 28
Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42
Change From Baseline in CSF Neurofilament Light Chain
时间窗: Screening to Day 28
Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain
Change From Baseline in CSF Total Tau.
时间窗: Screening to Day 28
Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.
Change From Baseline in CSF Neurogranin
时间窗: Screening to Day 28
Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin
Change From Baseline in CSF YKL-40
时间窗: Screening to Day 28
Change from Baseline (screening) in cerebrospinal fluid YKL-40
Change From Baseline in CSF P-tau181
时间窗: Screening to Day 28
Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181
次要结局
- Paired Associates Learning Test(Day 1 to Day 28)
- Spatial Working Memory Test(Day 1 to Day 28)
- CSF IL-6, sTREM2, HMGB1, Albumin, IgG(Screening to Day 28)