An Open-label, Single-center Study to Evaluate the Safety and Test-retest Characteristics of [11C]MODAG-005 as PET Radioligand for Imaging Pathological Alpha-synuclein Deposition in the Brains of Patients With Parkinson's Disease (PD) or Multiple System Atrophy (MSA) Compared to Age-matched Healthy Controls (AMHC) - Pilot Phase
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- MODAG GmbH
- 入组人数
- 9
- 试验地点
- 1
研究概览
简要总结
This is an open-label, single-center Phase 1 study evaluating the safety, tolerability, and test-retest characteristics of [11C]MODAG-005, an investigational positron emission tomography/computed tomography (PET/CT) radioligand intended to image pathological alpha-synuclein deposition in the brain. The study will enroll participants with Parkinson's disease (PD), participants with multiple system atrophy (MSA), and age-matched healthy controls (AMHC).
Participants with PD or MSA will undergo two [11C]MODAG-005 PET/CT imaging sessions: one baseline scan and one follow-up scan 7 to 48 days later. Age-matched healthy controls will undergo one baseline scan. A subset of PD and MSA participants will receive a single oral dose of anle138b (Emrusolmin) before the second scan to evaluate tracer uptake under blocking conditions. The primary objective is to assess the safety and tolerability of [11C]MODAG-005. Secondary objectives include evaluating whether [11C]MODAG-005 PET imaging can distinguish participants with MSA or PD from age-matched healthy controls, distinguish PD from MSA, and determine test-retest variability of PET outcome measures.
详细描述
This is an open-label, single-center Phase 1 study evaluating [11C]MODAG-005, an investigational Positron Emission Tomography (PET) radioligand for imaging pathological alpha-synuclein deposition in the brain. The study will enroll participants with Parkinson's disease (PD), participants with multiple system atrophy (MSA), and age-matched healthy controls (AMHC).
Participants with PD or MSA will undergo two [11C]MODAG-005 PET/CT scans: a baseline scan and a follow-up scan 7 to 48 days later. Age-matched healthy controls will undergo one baseline PET/CT scan. A subset of PD and MSA participants will receive a single oral dose of 300 mg anle138b (Emrusolmin) before the second scan to evaluate tracer uptake under blocking conditions.
The primary objective is to assess the safety and tolerability of [11C]MODAG-005 based on adverse events, vital signs, physical examinations, laboratory tests, and electrocardiograms. Secondary objectives include evaluating whether [11C]MODAG-005 PET imaging can distinguish MSA from healthy controls, PD from healthy controls, and PD from MSA, and assessing test-retest variability of PET imaging measures.
Exploratory analyses will assess tracer uptake with and without anle138b blocking, blood radioactivity and metabolite profiles, image-derived input functions, visual PET reads, and relationships between PET signal and clinical measures. Total study participation will last up to 12 weeks from screening to final follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Key inclusion criteria: Patients with MSA fulfilling both the criteria for probable MSA (Gilman et al., 2008) and clinically established MSA (Wenning et al., 2022), patients with PD fulfilling the criteria for clinically established PD (Postuma et al., 2015) or age-matched healthy controls (AMHC).
排除标准
- •Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness equivalent to CTC v5.0 (common toxicity criteria) toxicities greater than grade
- •Evidence of clinically significant disease that is expected to interfere with cognitive assessments or the ability to complete the trial procedures as judged by the investigator.
- •Clinically significant renal and hepatic dysfunction as judged by the investigator.
- •Known hypersensitivity to the active substance or to any of the excipients of [11C]MODAG-005 solution for injection.
- •Known hypersensitivity to the active substance or to any of the excipients in anle138b (Emrusolmin) capsules.
- •Participant has received an investigational drug within 3 months of screening.
- •Blood donations within 7 days before enrolment.
- •Pregnant (see 9.1.5) or breast-feeding or having the intention of getting pregnant. Female participants of childbearing potential and male participants with female partners of childbearing potential not willing to practice effective contraception during the trial period and for 90 days following each PET/CT scan.
- •Unsuitable veins for repeated venipuncture.
- •Contraindication to blood sampling and/or arterial cannulation, including but not limited to allergy to local anesthetics, peripheral vascular disease, Raynaud's phenomenon as determined by abnormal Allen's test on both arms or abnormal coagulation profile at screening. If Allen's test should be "abnormal" on both arms, the participant will not be eligible for arterial sampling, but will participate in the remaining assessments.
- •MRI exclusion criteria include but not limited to: findings of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct >1 cm^3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the Fluid-Attenuated Inversion Recov ery (FLAIR) sequence that is >20 mm in any dimension), infectious disease, space-occupying lesions normal pressure hydrocephalus or any other abnormalities associated with central nervous system (CNS) disease. Findings that are expected to be present in the PD and MSA participants (e.g. absence of swallow tail sign, presence of regional atrophy or hot cross bun sign) do not lead to exclusion of these participants.
- •Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.
- •Unwilling and/or unable to cooperate with trial procedures.
- •Exclusion criteria for age-matched healthy controls:
- •Relevant hepatic parameters above upper limit of normal (ULN), i.e., glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), bilirubin
- •Relevant renal parameters outside normal limits, i.e., serum creatinine and blood urea nitrogen (BUN) above ULN; urinary albumin-creatinine ratio (uACR) below lower limit of normal (LLN)
- •Systolic blood pressure <90 or >140 mmHg; diastolic blood pressure <45 or >90 mmHg; heart rate <50 or >95 beats per minute (BPM)
研究组 & 干预措施
Parkinson´s Disease (PD), Multiple System Atrophy (MSA), Healthy controls (HC)
Each participant with PD and each participant with MSA will receive two injections of up to 18 mL of [11C]MODAG-005 solution for injection with 40 - 400 MBq within 12 weeks. Each HC will receive one injection of up to 18 mL of [11C]MODAG-005 solution for injection with 40 - 400 MBq.
干预措施: [11C]MODAG-005 (Drug)