Imaging of a Radiolabeled Antibody for HIV-1

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

This study is testing a special imaging technique using a tiny dose of a radiolabeled antibody in people with HIV and healthy volunteers to see how it spreads in the body and if there are differences between the two groups.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT03729752 on ClinicalTrials.gov

What this trial studies

This exploratory imaging study involves administering a microdose of 89Zr-DFO-VRC01 to HIV-infected individuals and healthy volunteers to assess dosimetry and tissue distribution through whole-body PET-MR imaging. Participants will undergo up to four imaging sessions at specified intervals to evaluate the pharmacokinetics and radiation exposure of the radiolabeled antibody. The study aims to identify differences in PET activity between HIV-infected and uninfected individuals, which may inform future research on HIV persistence and treatment. The study is divided into two phases, with Phase 2 contingent on findings from Phase 1.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older who are either HIV-infected with specific viral load criteria or HIV-uninfected individuals.

Not a fit: Patients who are not eligible due to contraindications for MRI or those with undetectable HIV viral loads may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of HIV persistence and inform future therapeutic strategies.

How similar studies have performed: While this approach is exploratory, similar imaging studies have shown promise in understanding viral infections, though this specific methodology is novel.

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

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

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Timothy Henrich, MD — University of California, San Francisco
• Study coordinator: Timothy Henrich, MD

Conditions HIV-1-infection; PET scan; MRI; Viremia; Antiretroviral therapy