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Imaging Immune Activation in HIV by PET-MR

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ClinicalTrials.gov Identifier: NCT03684655
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : March 25, 2021
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, San Francisco
Information provided by (Responsible Party):
CellSight Technologies, Inc.

Tracking Information
First Submitted Date  ICMJE September 24, 2018
First Posted Date  ICMJE September 26, 2018
Last Update Posted Date March 25, 2021
Actual Study Start Date  ICMJE September 21, 2018
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
Anatomical distribution of [18F]F-AraG [ Time Frame: 1-4 hours ]
Anatomical distribution of [18F]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy as determined by PET-MR imaging.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • [18F]F-AraG uptake in early and later-treated HIV infection [ Time Frame: 1-4 hours ]
    Determine if [18F]F-AraG PET-MRI is able to detect differences in T cell activation in early versus late treated HIV infection, and between HIV infected and historical HIV-uninfected controls
  • Correlate [18F]F-AraG uptake with measures of HIV persistence [ Time Frame: 1-2 weeks ]
    Determine if [18F]F-AraG uptake correlates with direct blood and tissue measures of HIV reservoir size and activity in the above cohorts/studies.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Imaging Immune Activation in HIV by PET-MR
Official Title  ICMJE Imaging Immune Activation in HIV Infection
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Adults with HIV Infection taking or not taking antiretroviral therapy
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE HIV Infections
Intervention  ICMJE Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)
[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.
Other Name: VisAcT
Study Arms  ICMJE Experimental: [18F]F-AraG

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

Trade name: VisAcT

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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2021
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 month prior to enrollment.

    (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Timothy J Henrich, MD 415-206-5518 timothy.henrich@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03684655
Other Study ID Numbers  ICMJE 16-20302
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data from primary and secondary outcome measures will be shared.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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.
Responsible Party CellSight Technologies, Inc.
Study Sponsor  ICMJE CellSight Technologies, Inc.
Collaborators  ICMJE
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • University of California, San Francisco
Investigators  ICMJE
Principal Investigator: Timothy J Henrich, MD University of California, San Francisco
PRS Account CellSight Technologies, Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP