PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01)

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Volunteer<br>Four serial PET-MR scans over 120 hours following a single, bolus injection of [89]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01). | Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB<br>* Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.<br>* Other names: [89]Zr-DFO-VRC01;|
| Experimental: Viremic HIV-infected<br>Four serial PET-MR scans over 120 hours following a single, bolus injection of [89]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01). | Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB<br>* Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.<br>* Other names: [89]Zr-DFO-VRC01;|
| Experimental: Suppressed HIV-infected<br>A PET-MR scan following a single, bolus injection of [89]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01). | Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB<br>* Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.<br>* Other names: [89]Zr-DFO-VRC01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. | To determine the dosimetry and whole body distribution of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. Study Phase 1. | 120 hours | 
| 89Zr-DFO-VRC01 temporal uptake in healthy controls and HIV-infected participants with viral load >1000 c/mL. | To determine the differences in 89Zr-DFO-VRC01 temporal uptake in tissues in healthy volunteers versus HIV-infected, viremic participants. Study Phase 1. | 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 89Zr-DFO-VRC01 uptake in aviremic HIV-infected individuals. | To evaluate the uptake and tissue distribution of 89Zr-DFO-VRC01 in HIV-infected participants on suppressive antiretroviral therapy (ART) compared with HIV-infected, viremic individuals and healthy volunteers. Study Phase 2. | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1-infection, PET scan, MRI, Viremia, Antiretroviral therapy