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

NCT ID: NCT03729752

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2026-12-01

Brief Summary

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

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.

Conditions

HIV-1-infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DRUG

Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.

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).

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.

Suppressed HIV-infected

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.

Interventions

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

Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.

Intervention Type: DRUG

Other Intervention Names

[89]Zr-DFO-VRC01

Eligibility Criteria

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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

amfAR, The Foundation for AIDS Research

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Timothy Henrich

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Timothy Henrich, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Timothy Henrich, MD

Role: CONTACT

timothy.henrich@ucsf.edu

4158-206-5518

Facility Contacts

Emily Fehrman, BS

Role: primary

emily.fehrman@ucsf.edu

415-476-4082 ext. 340

References

Beckford-Vera DR, Flavell RR, Seo Y, Martinez-Ortiz E, Aslam M, Thanh C, Fehrman E, Pardons M, Kumar S, Deitchman AN, Ravanfar V, Schulte B, Wu IK, Pan T, Reeves JD, Nixon CC, Iyer NS, Torres L, Munter SE, Hyunh T, Petropoulos CJ, Hoh R, Franc BL, Gama L, Koup RA, Mascola JR, Chomont N, Deeks SG, VanBrocklin HF, Henrich TJ. First-in-human immunoPET imaging of HIV-1 infection using 89Zr-labeled VRC01 broadly neutralizing antibody. Nat Commun. 2022 Mar 9;13(1):1219. doi: 10.1038/s41467-022-28727-5.

Reference Type: DERIVED

PMID: 35264559 (View on PubMed)

Other Identifiers

17-23507

Identifier Type: -

Identifier Source: org_study_id