PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants.
研究概览
简要总结
This is a single center exploratory imaging study involving one intravenous microdose of 89Zr-DFO-VRC01 followed by whole-body PET-MR imaging in HIV infected individuals and healthy volunteers. Imaging data will be obtained from up to four static PE-MR images in order to determine dosimetry and temporal tissue uptake/tissue distribution of 89Zr-DFO-VRC01. This is not a treatment study of the biological activity of 89Zr-DFO-VRC01 to impact HIV persistence.
详细描述
This will be a single-center pilot study to determine dosimetry and tissue uptake/distribution and pharmacokinetics of 89Zr-VRC01. Up to 18 uninfected and HIV-infected subjects who are either taking or not taking ART will receive a small IV dose of 89Zr-VRC01. After administration of IV 89Zr-VRC01, subjects will undergo up to 4 whole body PET/MR imaging at 2, 6, 24 and 72-120h to determine the pharmacokinetics and radiation dose exposure. The study involves two phases with the second phase only to be performed only if a difference between PET activity in one or more region of interest can be determined between participant groups Phase I (HIV infected, viremic participants and healthy volunteers). Initially, up to 6 individuals with plasma HIV RNA levels >1,000 copies/ml and up to 6 HIV-uninfected individuals will be administered 89Zr radiolabeled VRC01 followed by PET-MR imaging as above (Phase 1). If differences in PET activity in one or more imaging region of interest can be identified between infected and uninfected individuals, up to 6 individuals on suppressive ART will be administered 89Zr radiolabeled VRC01 followed by PET-MRI (Phase 2). Timing of the PET-MR scans will be determined based on the data from Phase 1.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Study Phase 1
- •Age ≥18 years, and
- •HIV uninfected, or
- •HIV infection, and
- •has an HIV viral load measurement within 12 months of study entry of >40 copies/mL, and
- •HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity (HIV infected participants only)
- •Study Phase 2
- •Age ≥18 years, and
- •HIV infection, and
- •Initiated a combination ART regimen and has HIV viral load measurements below the detection limit of a clinically approved PCR-based assay (e.g. <40 HIV-1 RNA copies/mL of blood), or
- •HIV infection, and
- •has an HIV viral load measurement within 12 months of study entry of >40 copies/mL, and
- •HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity, or
- •HIV uninfected
排除标准
- •Study Phase 1
- •For patients planning to be imaged on PET-MR scanner, exclusion criteria will include any contra-indication to MRI, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia
- •Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
- •Patients who have had a study involving radiation within six months of enrolling in this study
- •Patients who are pregnant (female patients of childbearing age will be tested prior to injection of imaging agent - positive test will exclude from participating in the study)
- •Screening absolute neutrophil count <1,000 cells/mm3, platelet count <70,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <40 mL/minute, aspartate aminotransferase >100 units/L, alanine aminotransferase >100 units/L.
- •Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)
- •Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months.
- •Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis
- •Study Phase 2
- •For patients planning to be imaged on PET-MR scanner, exclusion criteria will include any contra-indication to MRI, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia
- •Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
- •Patients who have had a study involving radiation within 12 months of enrolling in this study
- •Patients who are pregnant (female patients of childbearing age will be tested prior to injection of imaging agent - positive test will exclude from participating in the study)
- •Screening absolute neutrophil count <1,000 cells/mm3, platelet count <70,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <40 mL/minute, aspartate aminotransferase >100 units/L, alanine aminotransferase >100 units/L.
- •Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)
- •Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months.
- •Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis
研究组 & 干预措施
Healthy Volunteer
Four serial PET-MR scans over 120 hours following a single, bolus injection of [89]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01).
干预措施: [89]Zr-DFO-VRC-HIVMAB060-00-AB (Drug)
Viremic HIV-infected
Four serial PET-MR scans over 120 hours following a single, bolus injection of [89]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01).
干预措施: [89]Zr-DFO-VRC-HIVMAB060-00-AB (Drug)
Suppressed HIV-infected
A PET-MR scan following a single, bolus injection of [89]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01).
干预措施: [89]Zr-DFO-VRC-HIVMAB060-00-AB (Drug)
结局指标
主要结局
Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants.
时间窗: 120 hours
To determine the dosimetry and whole body distribution of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. Study Phase 1.
89Zr-DFO-VRC01 temporal uptake in healthy controls and HIV-infected participants with viral load >1000 c/mL.
时间窗: 120 hours
To determine the differences in 89Zr-DFO-VRC01 temporal uptake in tissues in healthy volunteers versus HIV-infected, viremic participants. Study Phase 1.
次要结局
- 89Zr-DFO-VRC01 uptake in aviremic HIV-infected individuals.(72 hours)
研究者
Timothy Henrich
Associate Professor of Medicine
University of California, San Francisco