Clinical trial NCT03684655: Imaging Immune Activation in HIV by PET-MR
Official title: Imaging Immune Activation in HIV Infection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV infection
Positron Emission Tomography
F-AraG
Magnetic Resonance Imaging
Lead sponsor: CellSight Technologies, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: University of California, San Francisco
First posted: 2018-09-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Adults with HIV Infection taking or not taking antiretroviral therapy
Primary purpose: DIAGNOSTIC

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.

Detailed description: The PET radiofluorinated imaging agent, \[18F\]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine; trade name VisAcT) localizes to sites of immune activation and is predominantly accumulated in proliferative T cells. As a result, there is interest in imaging residual immune activation in the setting of both treated and untreated HIV-1 infection, a disease in which chronic immune activation and inflammation may lead to significant morbidity, despite the use of otherwise suppressive ART.

The primary endpoint is to determine the anatomical distribution of \[18F\]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy.

Secondary objectives are to determine if \[18F\]F-AraG PET-MRI is able to detect differences in T cell activation between patients with early versus late treated HIV infection and to determine if \[18F\]F-AraG uptake correlates with direct blood and tissue measures of HIV reservoir size and activity in the above cohorts/studies.

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years
2. Ability to read and understand written informed consent document
3. 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.)
4. 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)

Exclusion Criteria:

1. 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. Individuals who have received systemic immune modifying therapy within 60 days of study enrollment (excluding HIV DNA vaccine).
4. 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)
5. Participants who are breastfeeding
6. 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).
7. Participants who have had prior allogeneic stem cell or solid organ transplant
8. 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.
9. Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months
10. Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis
11. Previously diagnosed myelodysplasia syndrome. or history of lymphoproliferative disease prior to study entry
12. 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
13. Active Hepatitis C virus (HCV) infection. Prior history of treated HCV infection with sustained virological response will be allowed.
14. Active systemic autoimmune diseases.
15. Routine clinical vaccination within 14 days of study entry

Primary outcomes:
measure: Anatomical distribution of [18F]F-AraG
timeFrame: 1-4 hours
Secondary outcomes:
measure: [18F]F-AraG uptake in early and later-treated HIV infection
timeFrame: 1-4 hours
measure: Correlate [18F]F-AraG uptake with measures of HIV persistence
timeFrame: 1-2 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Timothy J Henrich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.