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

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ClinicalTrials.gov Identifier: NCT03729752
Recruitment Status : Recruiting
First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Collaborator:
amfAR, The Foundation for AIDS Research
Information provided by (Responsible Party):
Timothy Henrich, University of California, San Francisco

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
HIV-1-infection Drug: [89]Zr-DFO-VRC-HIVMAB060-00-AB 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 Type : Interventional  (Clinical Trial)
Estimated 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 : November 1, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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 Name: [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 Name: [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 Name: [89]Zr-DFO-VRC01




Primary Outcome Measures :
  1. Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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), and
  4. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03729752


Contacts
Contact: Timothy Henrich, MD 4158-206-5518 timothy.henrich@ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94110
Contact: Enrique Martinez-Ortiz, BS    415-476-4082 ext 340    enrique.martinez-ortiz@ucsf.edu   
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

Responsible Party: Timothy Henrich, Associate Professor of Medicine, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03729752     History of Changes
Other Study ID Numbers: 17-23507
First Posted: November 5, 2018    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We do not plan on sharing IPD with other researchers.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Timothy Henrich, University of California, San Francisco:
HIV-1-infection
PET scan
MRI
Viremia
Antiretroviral therapy

Additional relevant MeSH terms:
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs