A Phase 1, Controlled, Open-label, Single Dose, Dose-escalation, Clinical Proof-of-concept Study of MRI Enhanced With ADx-001 (DSPE-DOTA-Gd Liposomal Injection) in Patients With Brain Amyloid Deposits as Demonstrated by Amyloid PET

Alzeca Biosciences, Inc.2 个研究点分布在 1 个国家目标入组 16 人开始时间: 2022年11月9日最近更新: 2025年8月13日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Alzeca Biosciences, Inc.
入组人数: 16
试验地点: 2
主要终点: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

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 study is a Phase 1, first-in-human, multi-center study to establish safety of ADx-001 in healthy volunteers, and safety and proof of concept in patients with confirmed amyloid plaques in the brain (confirmed by amyloid positron emission tomography (PET)). ADx-001 is a novel, intravenously delivered, Gd- containing molecularly targeted liposomal product that is being developed for use in contrast-enabled MR imaging of amyloid plaques.

详细描述

Alzheimer's disease (AD) is an age-related neurodegenerative disorder of the brain and the most common cause of dementia. It is characterized by the development of amyloid plaques and neurofibrillary tangles. The A/T/N diagnostic criteria for AD, published by the National Institutes for Aging and the Alzheimer's Association (2018) identify amyloid plaques as a necessary condition for Alzheimer's disease.

Magnetic resonance imaging (MRI) is an essential neuroimaging examination for patients with Alzheimer's disease. MRI allows for the exclusion of other causes of dementia, such as normal pressure hydrocephalus, brain tumors, subdural hematoma, or cerebrovascular disease. MRI also permits the assessment of the atrophy pattern which may provide additional diagnostic or predictive information. To date, however, MRI cannot prove the existence of amyloid plaques in the brain.

Recently, amyloid-targeting radiopharmaceuticals have been approved by several Regulatory Authorities for use with Positron Emission Tomography (PET) imaging. Amyloid PET imaging is a sensitive imaging biomarker for Alzheimer's disease, but PET is associated with radiation exposure and has limited availability.

ADx-001 is a novel, intravenously delivered, macrocyclic gadolinium (Gd)-based molecularly targeted liposomal product that is being developed for use in contrast-enabled MR imaging of amyloid plaques. ADx-001-enabled MRI is expected to allow the detection of amyloid plaques in the human brain with sensitivity that is comparable to amyloid PET imaging.

This study is a Phase 1, first-in-human, study to collect safety data and obtain proof-of-concept of ADx-001 in healthy volunteers and subjects with proven amyloid plaques. Data from this study will be used to support future clinical studies with ADx-001 in AD patients.

研究设计

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

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: 是

入选标准

•For healthy volunteers
•50-75 years old (inclusive)
•Women of child-bearing potential must have a negative serum pregnancy test and agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of the study and for 3 months after completion of dosing; men enrolled on this protocol must agree to use adequate contraception prior to study entry, for the duration of the study and for 3 months after completion of dosing; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
•Signed informed consent prior to any study specific tests or procedures
•Healthy, based on medical history, physical examination, electrocardiogram (ECG), and laboratory tests
•For patients with amyloid plaques in PET:
•59-85 years old inclusive
•Proven amyloid deposits in brain (amyloid PET)
•Women of child-bearing potential must have a negative serum pregnancy test and agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of the study and for 3 months after completion of dosing. Men enrolled on this protocol must agree to use adequate contraception prior to study entry and for 3 months after completion of dosing; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
•Willing and able to provide written informed consent
•The ability to provide consent determined and documented by a neurologist or psychiatrist.

排除标准

•For healthy volunteers
•Disturbances in fat metabolism [hyperlipemia, hyperlipoproteinemia or hypercholesterolemia (total cholesterol >260 mg/dL)]
•History of allergic reactions attributed to any of the components of ADx-001, liposomes, other gadolinium contrast agents, or any other component of the formulation
•Pathological liver function:
•Bilirubin > upper limit of normal, and/or
•AST (SGOT), ALT (SGPT) and Alkaline phosphatase > upper limit of normal
•Calculated creatinine clearance < 60 mL/min/1.73 m2 (CKD-EPI formula)
•Heart rate at rest <50 or >90 bpm
•Systolic blood pressure <100 or >140 mmHg
•Diastolic blood pressure <50 or >90 mmHg
•Clinically relevant ECG findings, e.g., PQ >220 ms, QTc >450 ms, QRS >120 ms, branch bundle block, any sign of coronary heart disease
•Unwillingness or inability to comply with procedures required in this protocol
•Subjects who are currently receiving any other investigational agent, or who have received an investigational agent within the last 10 half-lives of the investigational agent
•Having tested positive for COVID-19 within 4 weeks of inclusion
•Any known disposition for allergic, anaphylactoid, hypersensitivity or idiosyncratic reactions, e.g. any history of clinical signs of hypersensitivity reaction to any agent (including, but not limited to, any allergen, food, drug, chemical, or contrast agent)
•Use of systemic or topically active medication or herbal remedies, prescription or non-prescription, from screening to the first drug administration. Only use of contraceptives and occasional use of paracetamol, aspirin, or ibuprofen is permissible.
•Any severe disease within the last 4 weeks prior to the first study drug administration
•Any malignant tumor and history thereof within last 5 years
•Any other medical condition which, at the discretion of the investigator, would make study participation unadvisable
•Any clinically relevant finding at the physical examination
•Blood donation or plasmapheresis within 4 weeks prior to screening
•Women of child-bearing potential: pregnancy, positive pregnancy test, or lactation
•Positive human immunodeficiency virus antibodies (HIV-1/2 Ab), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab) tests
•Regular alcohol consumption equivalent to >20 g alcohol per day
•Urine screen positive for any drug
•Positive alcohol breath test
•Subject is in custody by order of an authority or a court of law
•Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site) or employee of the sponsor
•Criteria which, in the opinion of the investigator, preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject's safety
•For patients with amyloid plaques in PET:
•Disturbances in fat metabolism [hyperlipemia, hyperlipoproteinemia or hypercholesterolemia (total cholesterol >260 mg/dL)]
•History of allergic reactions attributed to any of the components of ADx-001, liposomes, other gadolinium contrast agents, or any other component of the formulation
•Patients with history of cancer treatment in the last 6 months or currently receiving cancer treatment
•Major surgery within four weeks prior to Screening
•History or presence of a neurological or psychiatric diagnosis other than AD (not limited to but including for example, stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, major depression, brain tumors, etc.) that in the opinion of the investigator may limit compliance with study requirements, or compromise protocol objectives in the opinion of the investigator and/or the sponsor
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise protocol objectives in the opinion of the investigator and/or the sponsor
•Unwillingness or inability to comply with procedures required in this protocol
•Patients who are currently receiving any other investigational agent, or who have received an investigational agent within the last 10 half-lives of the investigational agent
•Inability to undergo MRI
•Pathological coagulation status (PT-INR/PTT >1.5 times the upper limit of normal)
•Pathological hematologic status:
•Granulocyte < 1500 cells/mm3, and/or
•Platelet count < 150,000 (plt/mm3), and/or
•Hemoglobin < 10 g/dL
•Pathological liver function:
•Bilirubin > upper limit of normal, and/or
•AST (SGOT), ALT (SGPT) and Alkaline phosphatase > upper limit of normal
•Calculated creatinine clearance < 60 mL/min/1.73 m2 (CKD-EPI formula)
•Cannot tolerate the recommended pretreatment
•Having tested positive for COVID-19 within 4 weeks of inclusion