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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03729752
• Other study ID #: 17-23507
• Status: Recruiting
• Phase: Phase 1
• Start date: November 1, 2018
• Est. completion date: January 1, 2025

Study information

• Verified date: August 2023
• Source: University of California, San Francisco
• Contact: Timothy Henrich, MD
• Phone: 4158-206-5518
• Email: timothy.henrich[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 1, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1-infection
• Infections

Intervention

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

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	amfAR, The Foundation for AIDS Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	120 hours
Primary	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.	120 hours
Secondary	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.	72 hours