Imaging Immune Activation in HIV by PET-MR

NCT03684655 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 16-20302
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center exploratory imaging study involving one intravenous microdose of \[18F\]F-AraG followed by whole-body positron emission tomography-magnetic resonance (PET-MR) imaging in HIV infected individuals to determine the anatomical distribution of the PET tracer. Participants will be enrolled if they were treated during early or late HIV infection. In addition, individuals not on antiretroviral therapy (ART) or with HIV-1 plasma RNA levels \>5,000 copies/mL will be enrolled. Up to 30 participants will be enrolled with HIV.

Conditions

HIV Infections

Keywords

HIV infection; Positron Emission Tomography; F-AraG; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Anatomical distribution of [18F]F-AraG

  Anatomical distribution of \[18F\]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy as determined by PET-MR imaging.

  1-4 hours

Secondary Outcomes (2)

• [18F]F-AraG uptake in early and later-treated HIV infection

  1-4 hours

• Correlate [18F]F-AraG uptake with measures of HIV persistence

  1-2 weeks

Study Arms (1)

[18F]F-AraG

EXPERIMENTAL

radiofluorinated imaging agent, \[18F\]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Trade name: VisAcT

Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)

Interventions

[18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) DRUG

\[18F\]F-AraG is a radiolabeled high affinity substrate for deoxyguanosine kinase (dGK) and a low affinity substrate for deoxycytidine kinase (dCK), which are over-expressed in activated T cells.

Also known as: VisAcT

[18F]F-AraG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Ability to read and understand written informed consent document
• HIV infection, and Initiated a combination ART regimen, or, has never received ART, or, has received ART in the past, but has not been taking for a least 1 week prior to study imaging.
• (Of note, per Department of Health and Human Services (DHHS) guidelines, the protocol team will strongly recommend that all HIV+ participants initiate ART who not done so already, both for their own health and to prevent the transmission of HIV infection.)
• Laboratory evaluations obtained within 60 days prior to entry. i. Platelet count ≥100,000/mm3 ii. ANC \>1500/mm3 iii. Aspartate aminotransferase (AST) \<2 x ULN iv. Alanine aminotransferase (ALT) \<2 x ULN v. CD4+ T cell count \>100 cells/mm3 for HIV infected individuals vi. Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft-Gault equation: For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)\*
• For women, multiply the result by 0.85 = CrCl (mL/min)

You may not qualify if:

• Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
• Individuals who have received systemic immune modifying therapy within 60 days of study enrollment (excluding HIV DNA vaccine).
• Participants who are pregnant (female participants of childbearing age will be tested prior to injection of imaging agent at entry visit/initial visit - positive test will exclude from further participation in the study)
• Participants who are breastfeeding
• Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months), or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative urine or serum pregnancy test with a sensitivity of at least 25 mIU/mL performed at the entry/initial visit, and again within 24 hours prior to PET imaging. Females of reproductive potential will need to be on 2 forms of birth control (excluding withdrawal or timing methods).
• Participants who have had prior allogeneic stem cell or solid organ transplant
• Screening absolute neutrophil count \<1,500 cells/mm3, platelet count \<100,000 cells/mm3, hemoglobin \< 8 mg/dL, estimated creatinine clearance \<60 mL/minute, aspartate aminotransferase \>2 x ULN, alanine aminotransferase \>2 x ULN.
• 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
• Previously diagnosed myelodysplasia syndrome. or history of lymphoproliferative disease prior to study entry
• History of congestive heart failure as defined by physician documentation in the medical record at any time prior to screening that required medication for heart failure or that required medical management within 1 year prior to study entry
• Active Hepatitis C virus (HCV) infection. Prior history of treated HCV infection with sustained virological response will be allowed.
• Active systemic autoimmune diseases.
• Routine clinical vaccination within 14 days of study entry

Sponsors & Collaborators

• CellSight Technologies, Inc.: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• University of California, San Francisco: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94110, United States

RECRUITING

Related Publications (2)

• Franc BL, Goth S, MacKenzie J, Li X, Blecha J, Lam T, Jivan S, Hawkins RA, VanBrocklin H. In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis. Mol Imaging. 2017 Jan 1;16:1536012117712638. doi: 10.1177/1536012117712638.

  PMID: 28625080 BACKGROUND

• Ronald JA, Kim BS, Gowrishankar G, Namavari M, Alam IS, D'Souza A, Nishikii H, Chuang HY, Ilovich O, Lin CF, Reeves R, Shuhendler A, Hoehne A, Chan CT, Baker J, Yaghoubi SS, VanBrocklin HF, Hawkins R, Franc BL, Jivan S, Slater JB, Verdin EF, Gao KT, Benjamin J, Negrin R, Gambhir SS. A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Cancer Res. 2017 Jun 1;77(11):2893-2902. doi: 10.1158/0008-5472.CAN-16-2953.

  PMID: 28572504 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Timothy J Henrich, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy J Henrich, MD

CONTACT

415-206-5518; timothy.henrich@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Adults with HIV Infection taking or not taking antiretroviral therapy

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: September 26, 2018
• Study Start: September 21, 2018
• Primary Completion: October 1, 2025
• Study Completion: November 1, 2025
• Last Updated: October 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will become available 6 months following study completion.
• Access Criteria: Data access requests will be reviewed by the principal investigator and study co-investigators. Requesters will be required to sign a Data Access Agreement.

Locations

US (1)