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

Primary Purpose

HIV-1-infection

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional diagnostic trial for HIV-1-infection focused on measuring HIV-1-infection, PET scan, MRI, Viremia, Antiretroviral therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Study Phase 1

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

Study Phase 2

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

Exclusion Criteria:

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

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

Sites / Locations

University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Healthy Volunteer

Viremic HIV-infected

Suppressed HIV-infected

Arm 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).

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

Outcomes

Primary Outcome Measures

Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants.

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

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

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

89Zr-DFO-VRC01 uptake in aviremic HIV-infected individuals.

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.

Full Information

NCT ID

NCT03729752

First Posted

November 1, 2018

Last Updated

August 9, 2023

Sponsor

University of California, San Francisco

Collaborators

amfAR, The Foundation for AIDS Research

1. Study Identification

Unique Protocol Identification Number

NCT03729752

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2018 (Actual)

Primary Completion Date

October 31, 2024 (Anticipated)

Study Completion Date

January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Francisco

Collaborators

amfAR, The Foundation for AIDS Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1-infection

Keywords

HIV-1-infection, PET scan, MRI, Viremia, Antiretroviral therapy

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Healthy Volunteer

Arm Type

Active Comparator

Arm 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).

Arm Title

Viremic HIV-infected

Arm Type

Experimental

Arm 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).

Arm Title

Suppressed HIV-infected

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

[89]Zr-DFO-VRC01

Intervention Description

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

Primary Outcome Measure Information:

Title

Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants.

Description

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

Time Frame

120 hours

Title

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

Description

To determine the differences in 89Zr-DFO-VRC01 temporal uptake in tissues in healthy volunteers versus HIV-infected, viremic participants. Study Phase 1.

Time Frame

120 hours

Secondary Outcome Measure Information:

Title

89Zr-DFO-VRC01 uptake in aviremic HIV-infected individuals.

Description

Time Frame

72 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Study Phase 1 Age ≥18 years, and HIV uninfected, or HIV infection, and has an HIV viral load measurement within 12 months of study entry of >40 copies/mL, and HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity (HIV infected participants only) Study Phase 2 Age ≥18 years, and HIV infection, and 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 HIV infection, and has an HIV viral load measurement within 12 months of study entry of >40 copies/mL, and HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity, or HIV uninfected Exclusion Criteria: Study Phase 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 Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator Patients who have had a study involving radiation within six months of enrolling in this study 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) 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. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only) Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months. 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 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 Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator Patients who have had a study involving radiation within 12 months of enrolling in this study 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) 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. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only) Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months. Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Timothy Henrich, MD

Phone

4158-206-5518

timothy.henrich@ucsf.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy Henrich, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94110

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emily Fehrman, BS

Phone

415-476-4082

Ext

340

emily.fehrman@ucsf.edu

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

We do not plan on sharing IPD with other researchers.

Citations:

PubMed Identifier

35264559

Citation

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.

Results Reference

derived

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

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