A Phase 1/2 Study to Evaluate Safety, PK and Biodistribution of an Imaging Agent, 18F-OP-801, After Intravenous Administration to Patients With ALS, Alzheimer's Disease, Multiple Sclerosis, Parkinson's Disease and Healthy Volunteers

Ashvattha Therapeutics, Inc.3 个研究点分布在 1 个国家目标入组 65 人开始时间: 2023年2月2日最近更新: 2025年5月2日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: Ashvattha Therapeutics, Inc.
入组人数: 65
试验地点: 3
主要终点: The number of participants with treatment emergent adverse events (Safety and Tolerability)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a Phase 1/2 study to evaluate the safety and tolerability of 18F-OP-801 in subjects with ALS, AD, MS, PD and age-matched HVs. 18F-OP-801 is intended as a biomarker for PET imaging of activated microglia and macrophages in regions of neuroinflammation.

详细描述

Microglia and macrophages have emerged as key players in neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS) such as amyotrophic lateral sclerosis, Alzheimer's disease (AD), multiple sclerosis (MS) and Parkinson's disease (PD). Treatments that selectively target these cells will need to cross the blood-brain barrier (BBB) at levels high enough to produce therapeutic effects. Unfortunately, it is difficult to directly measure the amount of a therapeutic that actually reaches the CNS target tissue. Development of biomarkers that allow direct visualization of cellular targeting across the BBB could offer profound insight into drug actions on innate immune cells in the brain. Furthermore, the ability to track accumulation of activated microglia in the brain could allow early identification of patients at risk for neurodegenerative or neuroinflammatory disease, precise stratification of patients for clinical trials and an efficacy measure for therapies that target neuroinflammation.

Positron emission tomography (PET) is a noninvasive imaging technology that can provide quantitative biological information in vivo, and it plays an important role in disease diagnosis, therapy assessment, and drug development. PET allows evaluation of the biological process without pharmacological effects because the amount of radiotracer used in imaging studies is very low. Several PET diagnostics track neuroinflammation in the brain, but current methods are limited by high background signal in healthy tissues.

18F-OP-801 is selectively taken up only by activated but not resting microglia, offering the potential to detect neuroinflammation at lower levels and earlier stages of disease than any current clinical PET radiotracer. We propose to use 18F-OP-801 to image activated microglia and brain macrophages in subjects with ALS, AD, MS, and PD to assess the compound's utility as a biomarker of neuroinflammation

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Diagnostic
盲法: None

入排标准

年龄范围: 18 Years 至 80 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Has the ability to understand and sign the written ICF and local medical privacy authorization forms, which must be obtained prior to the conduct of any study related procedures.
•Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at screening, based on the local laboratory's defined ranges.
•Female subjects of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) and all male subjects must agree to practice abstinence from sexual intercourse or use a medically accepted contraceptive regimen (including hormonal contraceptives) during their participation in the study and for 90 days (males) or 6 months (females) after Day
•Medically accepted contraceptive methods are defined as those with 90% or greater efficacy and are as follows:
•Male subjects: condoms or surgical sterilization of subject at least 26 weeks before the Screening Visit (i.e., vasectomy).
•Female subjects:
•Surgical sterilization at least 26 weeks before the Screening Visit (includes hysterectomy or bilateral tubal ligation, bilateral oophorectomy, or salpingectomy);
•Intrauterine device or diaphragm with spermicide for at least 12 weeks before the Screening Visit; or
•Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before the Screening Visit.
•If male, subjects must agree to abstain from sperm donation through 90 days after the Day 1 Visit.
•Female subjects may not be pregnant, lactating, or breastfeeding.
•Female subjects of childbearing potential must have negative result for pregnancy test at Screening and Check-in.
•Subjects must have an estimated glomerular filtration rate (eGFR) of >45 mL/min/1.73m2 at Screening.
•C-reactive protein level ≤10 mg/dL.
•Subjects must be willing and able to abide by all study requirements and restrictions.
•Inclusion Criteria Specific to ALS Subjects:
•Adult (Age 18 to 80, inclusive) at the Screening Visit
•Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by the modified El Escorial criteria.
•Forced vital capacity (FVC) of ≥50%; or if in the opinion of the investigator can lay flat for up to 90 minutes. If FVC has been performed within the past 6 months, this data may be used at the discretion of the investigator.
•For ALS subjects, medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
•Inclusion Criteria Specific to AD Subjects
•Adult (Age 40 to 80, inclusive) at the Screening Visit
•Clinical diagnosis of early stage dementia, Alzheimer type, plus positive Aβ and tau PET imaging, cerebrospinal fluid (CSF) and/or plasma biomarkers consistent with 2018 NIA-AA criteria
•MMSE score >20 at Screening
•AD medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
•Inclusion Criteria Specific to MS Subjects:
•Adult (Age 18 to 70, inclusive) at the Screening Visit
•MS medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
•Inclusion criteria specific to subjects with RRMS:
•Diagnosis of RRMS based on 2017 McDonald criteria
•If not newly diagnosed, subjects should have at least 1 documented relapse in the last 24 months.
•"Active disease" subjects should have at least 1 Gadolinium-enhancing (Gd+) T1-weighted brain or spinal cord lesion at Screening MRI.
•"Disease in remission" subjects should have no Gd+ T1-weighted brain or spinal cord lesions at Screening MRI and stable clinical symptoms for at least 3 months prior to Day
•EDSS score between 2.0 and 5.5 inclusive at Screening
•Inclusion criteria specific to subjects with progressive MS:
•Diagnosis of PPMS or SPMS based on 2017 McDonald criteria
•EDSS score between 3.0 and 6.5 inclusive at Screening
•No evidence of relapse in the prior 6 months
•Neurological exam and symptom stability for ≥30 days prior to Day 1
•Documented evidence of disability progression in the past 24 months not temporally related to a relapse
•Inclusion Criteria Specific to PD Subjects:
•Adult (Age 55 to 80, inclusive) at the Screening Visit
•Diagnosis of definite, idiopathic Parkinson's disease according to UK Parkinson's Society Brain Bank diagnostic criteria
•PD medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
•Overall Exclusion Criteria - For All Subjects:
•Subjects meeting any of the following criteria will be excluded from this study:
•Body weight >120 kg
•Evidence of clinically significant or past medical history of hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal, hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies) or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism or excretion of study drug or place the subject at an unacceptable risk as a participant in this study
•History of recurrent kidney or liver malignancy
•Pacemaker or defibrillator or any non-removable metallic foreign objects in the body not compatible with MRI
另有 23 项未显示

排除标准

未提供