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

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 1

Conditions: HIV-1-infection

Treatments: Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB

Study type: Interventional

Funder types: Other

Identifiers

NCT03729752

17-23507

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Study Phase 1

1. Age ≥18 years, and
2. HIV uninfected, or
3. HIV infection, and
4. has an HIV viral load measurement within 12 months of study entry of >40 copies/mL, and
5. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity (HIV infected participants only)

Study Phase 2

1. Age ≥18 years, and
2. HIV infection, and
3. 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
4. HIV infection, and
5. has an HIV viral load measurement within 12 months of study entry of >40 copies/mL, and
6. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity, or
7. HIV uninfected

Exclusion criteria

Study Phase 1

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
2. Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
3. Patients who have had a study involving radiation within six months of enrolling in this study
4. 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)
5. 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.
6. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)
7. Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months.
8. 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

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
2. Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
3. Patients who have had a study involving radiation within 12 months of enrolling in this study
4. 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)
5. 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.
6. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)
7. Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months.
8. Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Healthy Volunteer

Active Comparator group

Description:

Four serial PET-MR scans over 120 hours following a single, bolus injection of \[89\]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01).

Treatment:

Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB

Viremic HIV-infected

Experimental group

Description:

Four serial PET-MR scans over 120 hours following a single, bolus injection of \[89\]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01).

Treatment:

Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB

Suppressed HIV-infected

Experimental group

Description:

A PET-MR scan following a single, bolus injection of \[89\]Zr-DFO-VRC-HIVMAB060-00-AB (89Zr-DFO-VRC01).

Treatment:

Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB