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

Sponsor
University of California, San Francisco (Other)
Overall Status
Recruiting
CT.gov ID
NCT03729752
Collaborator
amfAR, The Foundation for AIDS Research (Other)
18
Enrollment
1
Location
3
Arms
36
Anticipated Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01)
Actual Study Start Date :
Nov 1, 2018
Anticipated Primary Completion Date :
Oct 31, 2021
Anticipated Study Completion Date :
Oct 31, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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).

Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB
Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.
Other Names:
  • [89]Zr-DFO-VRC01

    		•
    Experimental: 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).

    Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB
    Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.
    Other Names:
  • [89]Zr-DFO-VRC01

    		•
    Experimental: Suppressed HIV-infected

    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
    Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.
    Other Names:
  • [89]Zr-DFO-VRC01

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. [120 hours]

      To determine the dosimetry and whole body distribution of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. Study Phase 1.

    2. 89Zr-DFO-VRC01 temporal uptake in healthy controls and HIV-infected participants with viral load >1000 c/mL. [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.

    Secondary Outcome Measures

    1. 89Zr-DFO-VRC01 uptake in aviremic HIV-infected individuals. [72 hours]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, San Francisco San Francisco California United States 94110

    Sponsors and Collaborators

    • University of California, San Francisco
    • amfAR, The Foundation for AIDS Research

    Investigators

    • Principal Investigator: Timothy Henrich, MD, University of California, San Francisco

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Timothy Henrich, Associate Professor of Medicine, University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT03729752
    Other Study ID Numbers:
    • 17-23507
    First Posted:
    Nov 5, 2018
    Last Update Posted:
    Mar 12, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Timothy Henrich, Associate Professor of Medicine, University of California, San Francisco
    HIV-1-infection
    PET scan
    MRI
    Viremia
    Antiretroviral therapy
    Additional relevant MeSH terms:
    Infections

    Study Results

    No Results Posted as of Mar 12, 2021