We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
ClinicalTrials.gov Menu

Selection of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent HIV Proviruses (FXR#2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT05219916
Recruitment Status : Terminated (It is unlikely that the scientific question will ever be answered. Thus, it would be considered unethical to continue the trial.)
First Posted : February 2, 2022
Last Update Posted : March 13, 2023
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE January 21, 2022
First Posted Date  ICMJE February 2, 2022
Last Update Posted Date March 13, 2023
Actual Study Start Date  ICMJE April 12, 2022
Actual Primary Completion Date July 22, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2022)
Measurement of the reactivation level and the EC50 of the optimized molecules. [ Time Frame: At inclusion. ]
Measurement of reactivation level compared to that obtained with the reference LRA Ingenol, and EC50 of molecules derived from active leads and preselected on viral and ADMET criteria in vitro to allow the choice of the best molecule for future clinical development. PBMCs (peripheral blood mononuclear cells) and rCD4+Tcells will be isolated and treated with the test molecules for 3 days. The treated cells will be incubated to determine the number of cells producing HIV/ million of rCD4+ T cells. FXR ligands will be used at 10 µM. Dose-response assay will be carried out to determine the EC50 (half maximal effective concentration) of the active molecules and the best molecules in the final selection will be tested in combination with inhibitors of the metabolic pathway to confirm their specificity of action. Molecules derived from the 2 leads will be screened in successive series.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Selection of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent HIV Proviruses
Official Title  ICMJE Selection of Farnesoid X Receptor (FXR) Ligands as Latency Reversal Agents (LRA) of Latent HIV Proviruses in Circulating CD4+ T Lymphocytes Isolated From Patients With Undetectable HIV Viremia Under cART (Combined Antiretroviral Treatments)
Brief Summary

The FXReservoir#1 study (NCT03618862) showed that certain FXR ligands reactivate latent viruses in the reservoir circulating in all HIV+ patients tested. These molecules appear as latency reversal agents (LRA) of silent viruses of the HIV reservoir. They can be part of the strategy to eradicate this reservoir, responsible for recurrences of the infection when combined anti-retroviral treatments are stopped.

Two effective leads have been identified on in vitro tests and on ex vivo reactivation using FXReservoir#1. These molecules come from a chemical library of FXR ligands developed by the Inserm team behind the discovery of a role for FXR in viral infections.

A first series of optimized molecules derived from these leads has been synthesized; these molecules, after screening on viral and ADMET (Absorption, Distribution, Metabolisme, Excretion and Toxicity) in vitro tests, must be tested ex vivo on CD4+ lymphocytes from the circulating peripheral reservoir of HIV+ patients in order to select the best molecules with LRA activity. This step is essential before considering the clinical development of an LRA.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Descriptive physiopathological study
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Human Immunodeficiency Virus I Infection
Intervention  ICMJE Procedure: Blood collection.

One additional 80 mL blood collection will be collected from HIV patients during a scheduled blood collection as part of their regular follow-up.

Samples will be transported within 3-5 hours by a carrier approved for the transportation of infectious biological samples from the Croix Rousse hospital to the P3 laboratory of the Ecole Normale Supérieure, Lyon for analysis.

Study Arms  ICMJE Experimental: Adult patients infected by HIV, controlled under treatment.
Blood sample collection from HIV controlled patients during their scheduled consultation, after obtaining their non-opposition by an investigator.
Intervention: Procedure: Blood collection.
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: March 9, 2023)
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2022)
Actual Study Completion Date  ICMJE July 22, 2022
Actual Primary Completion Date July 22, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Criteria relating to the population studied: patients aged 18 to 65 years old, men or women, regardless of ethnic origin.
  • Nosological criteria: HIV-1 infection, documented by a complete western blot and/or a detectable viral load at the time of diagnosis, regardless of the viral subtype.
  • Pathology severity and progression criteria: patients with a CD4+ count greater than 500 elements/mm3 at the last follow-up visit prior to inclusion in the study. Undetectable viral load for at least six months on stable treatment.
  • Criteria relating to treatments/strategies/procedures: Current cART treatment mandatory, regardless of the combination of anti-retrovirals, effective with undetectable viral load. The number of processing lines is not limited.
  • Criteria relating to regulation: Absence of opposition

Exclusion Criteria:

  • Criteria relating to the population studied: pregnant or breastfeeding women
  • Criteria relating to contraindications to the protocol explorations:

Acute or chronic anaemias Acute infections, fever Coagulation disorders, patients taking anticoagulants

- Criteria relating to regulation: Subjects placed under judicial safeguard, guardianship or curatorship Subjects participating in another research with an ongoing exclusion period.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT05219916
Other Study ID Numbers  ICMJE 69HCL21_0846
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hospices Civils de Lyon
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hospices Civils de Lyon
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tristan FERRY, MD-PhD Service des maladies infectieuses et tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date March 2023

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