Drug Database: Tucidinostat

What is tucidinostat?What is tucidinostat?

What is tucidinostat?

Tucidinostat is an investigational drug that is being studied as part of a strategy to cure HIV infection. Tucidinostat belongs to a group of HIV drugs called latency-reversing agents.³

To learn how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How do latency-reversing agents work?How do latency-reversing agents work?

How do latency-reversing agents work?

Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that the virus can remain hidden and inactive (latent) inside certain cells of the immune system (such as resting CD4 cells) for many months or even years. The cells where latent HIV hides are known as the latent HIV reservoir. Because HIV in this latent state is inactive, the immune system cannot detect the virus, and the antiretroviral (ARV) drugs that are used to treat HIV have no effect on it.^4–6

Latency-reversing agents work by drawing HIV out of its latent state within resting CD4 cells. Once the latent HIV is reactivated, the CD4 cells that harbor the virus are more likely to be recognized and killed by the body’s immune system or may be killed by certain HIV therapies, such as those that can enhance the body’s immune response to HIV. Researchers hope that the combined use of tucidinostat and other HIV-fighting strategies, including ongoing antiretroviral therapy (ART), may fully eliminate HIV from the body.^4–6 To learn more, see the HIVinfo What is a Latent HIV Reservoir? fact sheet.

Select clinical trials of tucidinostatSelect clinical trials of tucidinostat

Select clinical trials of tucidinostat

Study Names: CHARTER; NCT02513901

Phase: 1b/2a
Status: This study has been completed.
Location: China
Purpose: The purpose of this study was to look at the safety of tucidinostat and to see whether tucidinostat added to ART could reactivate latent HIV and help reduce latent HIV reservoir size.^7,8
Selected Study Results: Results published in the journal HIV Medicine (2020) showed that tucidinostat added to ART in seven participants with viral suppression robustly reactivated latent HIV and modestly reduced the latent HIV reservoir size.^8,9

Study Name: NCT02902185

Phase: 2/3
Status: This study has been completed.
Location: China
Purpose: The purpose of this study was to confirm the effectiveness of tucidinostat plus ART in reactivating latent HIV and reducing latent HIV reservoir size.^3,10

Study Name: NCT04985890

Phase: 2
Status: See the ClinicalTrials.gov record for this study's status.
Location: Not available
Purpose: The purpose of this study is to evaluate the safety of tucidinostat plus the CD4 attachment inhibitor semzuvolimab (UB-421) and the ability of this regimen in reducing the latent HIV reservoir in participants undergoing an analytical treatment interruption of ART.¹¹

Study Name: NCT05056974

Phase: 2
Status: This study has been completed.
Location: Taiwan
Purpose: The purpose of this study was to evaluate the safety and efficacy of tucidinostat plus semzuvolimab (UB-421) monotherapy in changing the latent HIV reservoir in participants who underwent an analytical treatment interruption of ART.¹²

Study Name: NCT05129189

Phase: 2
Status: This study is currently recruiting participants.
Location: China
Purpose: The purpose of this study is to evaluate whether ASC22 (an investigational antibody therapy) combined with tucidinostat can reduce latent HIV reservoir size.¹³
Selected Study Results: Results presented at IAS 2023 showed that ASC22 combined with tucidinostat activated latent HIV and reduced the size of the latent HIV reservoir only in participants with enhanced T-cell function.¹⁴

For more details on the studies listed above, see the Health Professional version of this drug summary.

In addition, a Phase 1 study (NCT03980691) evaluated whether tucidinostat used in combination with gene therapy could reduce the size of the latent HIV reservoir in participants on suppressive ART. This study has been completed.¹⁵

What side effects might tucidinostat cause?What side effects might tucidinostat cause?

What side effects might tucidinostat cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of tucidinostat listed above.

CHARTER (NCT02513901)

In this Phase 1b/2a study, no significant side effects occurred, and all reported side effects were mild in severity. Rash and fatigue/sleepiness were each reported in one person.^8,16

NCT05129189

In this Phase 2 study, 15 participants were enrolled to receive subcutaneous ASC22 (an investigational antibody therapy) and oral tucidinostat while maintaining antiretroviral therapy (ART). ASC22 and tucidinostat were well tolerated. Nine drug-related side effects were reported, all of which were mild and resolved without treatment.¹⁴

Because tucidinostat is still being studied, information on possible side effects of the drug is not complete. As testing of tucidinostat continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying tucidinostat?Where can I get more information about clinical trials studying tucidinostat?

Where can I get more information about clinical trials studying tucidinostat?

More information about tucidinostat-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem compound summary for CID 12136798, tucidinostat. Accessed January 31, 2024
2. Huya Bioscience International: Press Release, dated March 6, 2007. HUYA Bioscience licenses chidamide cancer compound from Chipscreen Biosciences. Accessed January 31, 2024
3. Treatment Action Group website. Research toward a cure trials. Accessed January 31, 2024
4. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096. Accessed January 31, 2024
5. Rasmussen TA, Tolstrup M, Winckelmann A, Østergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccines Immunother. 2013;9(4):790–799. Accessed January 31, 2024
6. National Institute of Allergy and Infectious Diseases (NIAID). HIV viral eradication. Accessed January 31, 2024
7. Tang-Du Hospital. Safety and efficacy of the histone deacetylase inhibitor chidamide in combination with antiretroviral therapy for eradication of the latent HIV-1 reservoir (CHARTER). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 30, 2015. NLM Identifier: NCT02513901. Accessed January 31, 2024
8. Sun Y, Li J, Ma C. Chidamide disrupts and reduces HIV-1 latency in patients on suppressive antiretroviral therapy. Slides presented at: International AIDS Conference; July 23-27, 2018; Amsterdam, Netherlands. Accessed January 31, 2024
9. Li JH, Ma J, Kang W, et al. The histone deacetylase inhibitor chidamide induces intermittent viraemia in HIV-infected patients on suppressive antiretroviral therapy. HIV Med. 2020;21(11):747-757. doi:10.1111/hiv.13027. Accessed January 31, 2024
10. Tang-Du Hospital. Efficacy of the histone deacetylase inhibitor chidamide in combination with antiretroviral therapy for reactivation of the latent HIV-1 reservoir: a randomized controlled clinical trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 6, 2016. NLM Identifier: NCT02902185. Accessed January 31, 2024
11. UBP Greater China (Shanghai) Co., Ltd. A proof of concept study to evaluate the safety and efficacy of UB-421 in combination with Chidamide for reduction of HIV reservoir as compared to UB-421 alone in ART stabilized HIV-1 patients who undergo ART interruption.  In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 8, 2021. NLM Identifier: NCT04985890. Accessed January 31, 2024
12. United BioPharma. A Phase II proof-of-concept trial to evaluate the safety and efficacy of UB-421 plus Chidamide for the shock-block-kill mechanism in changing HIV reservoirs among ART stabilized HIV-1 patients who undergo ART interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 18, 2021. NLM Identifier: NCT05056974. Accessed January 31, 2024
13. Shanghai Public Health Clinical Center. Functional cure study of anti-PD-L1 antibody ASC22 in combination with chidamide. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 15, 2021. NLM Identifier: NCT05129189. Accessed January 31, 2024
14. Wu L, Zheng Z, Xun J, et al. Anti-PD-L1 antibody ASC22 in combination with chidamide potentiates HIV latency reversal and immune function from ART-suppressed individuals: a single center, single-arm, phase II study. Poster presented at: IAS Conference on HIV Science; July 23-26, 2023; Brisbane, Australia and Virtual. Poster LBEPB18. Accessed January 31, 2024
15. Guangzhou 8th People’s Hospital. Effect of chidamide combined with CAT-T or TCR-T cell therapy on HIV-1 latent reservoir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 7, 2019. NLM Identifier: NCT03980691. Accessed January 31, 2024
16. Sun Y, Li J, Ma J. Chidamide reactivates and diminishes latent HIV-1 DNA in patients on suppressive antiretroviral therapy. Abstract presented at: International AIDS Conference; July 23-27, 2018; Amsterdam, Netherlands. Abstract WEAA0101. Accessed January 31, 2024