Human Immunodeficiency Virus I InfectionFXR#2NCT05219916
Selection of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent HIV Proviruses
A study testing Blood collection. in people with Human Immunodeficiency Virus I Infection, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Immunodeficiency Virus I Infection
- What is being tested?
- Blood collection.
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteFrance
- Study dates
- 12 Apr 2022to 22 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Service des maladies infectieuses et tropicales Hôpital de la Croix Rousse
Lyon, 69004
About this study
Official title: 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)
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.
- Conditions
- Human Immunodeficiency Virus I Infection
- Being tested
- Blood collection.
- Keywords
- HIV, LRA, FXR, Reactivation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collection.Procedure or surgery
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 group | Role | What they receive |
|---|---|---|
| Adult patients infected by HIV, controlled under treatment. | Experimental | Blood sample collection from HIV controlled patients during their scheduled consultation, after obtaining their non-opposition by an investigator. Receives: Procedure: Blood collection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of the reactivation level and the EC50 of the optimized molecules.
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.
Measured: At inclusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2022
- Study start12 Apr 2022
- Primary completion22 Jul 2022
- Study completion22 Jul 2022
Why it stopped: It is unlikely that the scientific question will ever be answered. Thus, it would be considered unethical to continue the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human Immunodeficiency Virus I InfectionStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Descriptive physiopathological study
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tristan FERRY, MD-PhD, Principal investigator, Service des maladies infectieuses et tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05219916
- Sponsor's protocol ID
- 69HCL21_0846
- Acronym
- FXR#2
- Status last verified
- Mar 2023
- First submitted
- 21 Jan 2022
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05219916
- Acronym / sponsor ID
- FXR#2 / 69HCL21_0846
- Conditions
- Human Immunodeficiency Virus I Infection
- Keywords
- HIV, LRA, FXR, Reactivation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: It is unlikely that the scientific question will ever be answered. Thus, it would be considered unethical to continue the trial.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 12 Apr 2022 (actual)
- Primary completion
- 22 Jul 2022 (actual)
- Study completion
- 22 Jul 2022 (actual)
- First posted
- 2 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Descriptive physiopathological study
| Arm | Type | Receives |
|---|---|---|
| Adult patients infected by HIV, controlled under treatment. | Experimental | Procedure: Blood collection.Blood sample collection from HIV controlled patients during their scheduled consultation, after obtaining their non-opposition by an investigator. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Procedure or surgery | Adult patients infected by HIV, controlled under treatment. |
Primary outcome
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.
Results and safety
The study was stopped early (reason given: It is unlikely that the scientific question will ever be answered. Thus, it would be considered unethical to continue the trial.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
Related trials for Human Immunodeficiency Virus I Infection
RecruitingObservational study
Evaluation of Patients With HAM/TSP
HTLV-I Infection, Tropical Spastic Paraparesis
RecruitingPhase 1
A Study to Investigate Pharmacokinetics, Safety and Tolerability of Long-Acting Cabotegravir Plus Recombinant Human Hyaluronidase PH20 in Healthy Adult Participants
HIV Infections
RecruitingPhase 1/2
Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Allogeneic Hematopoietic Cell Bone Marrow Transplantation Followed by Graft-versus-Host-Disease (GVHD) Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies ...
HIV, Hematologic Malignancies
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tristan FERRY, MD-PhD principal investigator
Service des maladies infectieuses et tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood collection. in people with Human Immunodeficiency Virus I Infection, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: It is unlikely that the scientific question will ever be answered. Thus, it would be considered unethical to continue the trial.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of the reactivation level and the EC50 of the optimized molecules. (time frame: At inclusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2023.