A Prospective, Multicentric, Randomized, Double Blind, Placebo Controlled Phase II Clinical Study to Compare the Safety and Efficacy of PMZ-1620 Therapy Along With Standard Supportive Care in Subjects of Mild to Moderate Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 5
- 主要终点
- Incidence of PMZ-1620 related adverse events
研究概览
简要总结
This is a prospective, multicentric, randomized, double blind, placebo controlled Phase II clinical study to compare the safety and efficacy of PMZ-1620 therapy along with standard supportive care in subjects with mild to moderate Alzheimer's disease.
详细描述
Alzheimer's is not just a disease of old age, approximately 200,000 Americans under the age of 65 having younger-onset Alzheimer's disease (AD). In 2015, there were approximately 29.8 million people worldwide with AD. The person with Alzheimer's disease can live an average of eight years after their symptoms become noticeable to others, but survival range is 4 to 20 years, depending on the age and other health conditions (www.alz.org). The pathophysiology of AD is related to the injury and death of neurons, initiating in the hippocampus brain region that is involved with memory and learning, then atrophy affects the entire brain. The cause of Alzheimer's disease is still poorly understood and about 70% of the risk is associated with genetic. Other risk factors may also associate with this like history of head injuries, depression, or hypertension. Like all types of dementia, Alzheimer's is also caused by brain cell death. Although AD is classified as a neurodegenerative dementia, considerable evidence links vascular dysfunction and vascular risk factors as pathogenesis of AD. However, it is a progressive brain cell death that happens over a course of time and treatments can't stop Alzheimer's from progressing, they can temporarily slow the worsening of dementia symptoms and improve quality of life for those with Alzheimer's and their caregivers (www.alz.org; www.who.int).
Sovateltide is an endothelin B (ETB) receptor agonist (previously used names IRL-1620, SPI-1620 and PMZ-1620; International Non-proprietary Name (INN) approved by WHO is sovateltide). Activation of ETB receptors with PMZ-1620 produces neurovascular repair and remodeling or neuroregeneration. There are hidden stem cells in the brain, which becomes active following injury to the brain. Intravenous administration of PMZ-1620 (sovateltide) augments the activity of neuronal progenitor cells in the brain to repair the damage by formation of new mature neurons and blood vessels. In addition, PMZ-1620 has anti-apoptotic activity and also increases cerebral blood flow.
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
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult males or females Aged 45 years through 85 years (have not had their 86th birthday)
- •Men and women with a diagnosis of Alzheimer's disease according to the clinical criteria
- •Women must be of non-childbearing potential, surgically sterile, or willing to use adequate birth control; men who are sexually active will also be required to use adequate birth control
- •Able to give consent for participation on their own or through their Legally Acceptable Representative
- •MRI/CT scan assessment within six months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions
- •MMSE score in between 11 to 26 in case of mild to moderate stage of Alzheimer's disease
- •Absence of major depressive disease according to Geriatric Depression Scale (GDS) of < 5
- •Previous decline in cognition for more than six months as documented in subject's medical records
- •Subject, who are on stable treatment with any of AD drugs are also eligible to participate in this study
- •Formal education for eight or more years
- •Subjects living at home or nursing home setting, without continuous nursing care
- •General health status acceptable for participation in a 6-months clinical trial
- •A caregiver available and living in the same household or interacting with the subject a sufficient time each week and available if necessary to assure administration of drug
- •Subjects with any other chronic conditions are stable and undergoing appropriate treatment
排除标准
- •Subjects who have a Mini Mental State Examination (MMSE) score of < 10
- •Subjects who have serious or unstable medical conditions that would exclude completion of all procedures and data collection for the study, or would be likely to preclude participation in a drug development trial
- •A current Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of active major depression, schizophrenia or bipolar disorder
- •Other infectious, metabolic or systemic diseases affecting the central nervous system
- •Subjects who have participated in a clinical trial investigating an anti-amyloid agent
- •Subjects who are currently participating in a clinical trial with an investigational drug
- •Subjects who, in the opinion of the physician, are otherwise unsuitable for this study
- •Clinically significant, advanced or unstable disease that may interfere with outcome measures, and which may bias the assessment of the clinical or mental status of the subject or put the subject at special risk
- •History of or screening brain MRI scan indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct > 1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma)
- •Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions within 6 months of Screening
- •Clinical or laboratory findings consistent with:
- •Other primary degenerative dementia,
- •Other neurodegenerative condition
- •Seizure disorder
- •Subjects, who are already taking sedatives, antidepressants, antipsychotics and antihistaminic medications
研究组 & 干预措施
Normal Saline
Patients will receive the best available standard of care. In control group, 3 doses of equal volume of normal saline will be administered as an IV bolus over 1 minutes every 3 hours ± 1 hour on day 1, the same dosing regimen will be repeated every month for 6 months post randomization.
干预措施: Normal Saline along with standard treatment (Drug)
PMZ-1620 (sovateltide)
Patients will receive the best available standard of care. In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an intravenous bolus over 1 minute every 3 hours ± 1 hour on day 1 (total dose/day: 0.9 µg/kg body weight), the same dosing regimen will be repeated every month for 6 months post randomization.
干预措施: PMZ-1620 (sovateltide) along with standard treatment (Drug)
结局指标
主要结局
Incidence of PMZ-1620 related adverse events
时间窗: 160 days
The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.
Number of patients not receiving full treatment due to intolerance to PMZ-1620
时间窗: 160 days
Tolerability will be determined by the number of patients that do not receive all the 18 doses of PMZ-1620.
次要结局
- Changes in clinical progression of AD as measured by Mini-Mental State Examination (MMSE)(160 days)
- Changes in neuropsychiatric inventory (NPI) Score(160 days)
- Changes in hippocampal atrophy using MRI/CT(160 days)
- Changes in electroencephalograms (EEGs)(160 days)
- Changes in Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog)(160 days)