Drug Database: Semzuvolimab

What is semzuvolimab?

Semzuvolimab is an investigational drug that is being studied to treat HIV infection.³

Semzuvolimab belongs to a group of HIV drugs called CD4 attachment inhibitors.³ CD4 attachment inhibitors work by attaching to a protein on the surface of immune cells. The protein is called the CD4 receptor. When semzuvolimab attaches to the CD4 receptor, HIV cannot attach to, enter, or infect the cell.⁴ This prevents HIV from multiplying and can reduce the amount of HIV in the body.

To learn about 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.

Select clinical trials of semzuvolimab

Study Names: Protocol A201-HIV; NCT01668043

Phase: 2a
Status: This study has been completed.
Location: Taiwan
Purpose: The purpose of this study was to look at two different dosages of semzuvolimab monotherapy in treatment-naive adults with HIV. Semzuvolimab’s safety and effectiveness in lowering viral load were assessed.⁵

Study Names: UBP-A202-HIV; NCT02369146

Phase: 2
Status: This study has been completed.
Location: Taiwan
Purpose: The purpose of this study was to evaluate the safety and effectiveness of two different dosages of semzuvolimab monotherapy as a substitute for antiretroviral therapy (ART).⁶
Selected Study Results: Results published in the New England Journal of Medicine (2019) showed that treatment with semzuvolimab monotherapy in participants with viral suppression was safe and effective. All participants maintained viral suppression while receiving semzuvolimab monotherapy during an analytical treatment interruption of ART (lasting 8 or 16 weeks).⁷

Study Names: UBP-A209-HIV; NCT03743376

Phase: 2
Status: This study has been completed.
Location: Taiwan
Purpose: The purpose of this study was to evaluate the safety of semzuvolimab and its effectiveness in reducing the HIV reservoir when used in combination with ART.⁸

Study Names: UBP-A205-HIV; NCT03164447

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 efficacy, safety, and tolerability of semzuvolimab when used first with an ART regimen that is not working, then with optimized background therapy (OBT).⁹

Study Names: UBP-A230-HIV; 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 semzuvolimab plus the latency-reversing agent tucidinostat and the ability of this regimen in reducing the latent HIV reservoir in participants undergoing an analytical treatment interruption of ART.¹⁰

Study Names: UBP-A218-HIV; NCT04404049

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 semzuvolimab and its effectiveness in reducing the latent HIV reservoir when used in combination with ART.¹¹

Study Names: UBP-A232-HIV; NCT05056974

Phase: 2
Status: This study has been completed. 
Location: Taiwan
Purpose: The purpose of this study was to evaluate the safety of semzuvolimab monotherapy plus the latency-reversing agent tucidinostat and the ability of this regimen in changing the latent HIV reservoir in participants undergoing an analytical treatment interruption of ART.¹² 

Study Name: NCT05582694

Phase: 2
Status: This study is currently recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the efficacy of semzuvolimab plus optimized background therapy in reducing viral load levels in participants with multidrug-resistant HIV.¹³

Study Names: UBP-A308-HIV; NCT04406727

Phase: 3
Status: See the ClinicalTrials.gov record for this study’s status.  
Location: Not available.
Purpose: The purpose of this study is to evaluate the effectiveness of semzuvolimab plus optimized background therapy in reducing viral load levels in participants with multidrug-resistant HIV.²

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

Additional studies evaluating semzuvolimab for HIV treatment are being conducted, including the following early-phase trials:

• UBP-A122-HIV (NCT04620304): A Phase 1 dose-escalation study to evaluate the safety, pharmacokinetics, and antiviral activity of a subcutaneous form of semzuvolimab in treatment-naive adults with HIV. This study has been completed.¹⁴
• UBP-A127-HIV (NCT04620291): A Phase 1 study to evaluate the safety, pharmacokinetics and antiviral activity of a subcutaneous form of semzuvolimab in adults with HIV who have viral suppression on ART and in adults with HIV who are treatment-naive. See the ClinicalTrials.gov record for this study’s status.¹⁵
   

What side effects might semzuvolimab cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the Phase 2 study UBP-A202-HIV (NCT02369146) discussed under the previous section, the most common side effect that was possibly or probably related to semzuvolimab was mild or moderate skin rash, and it occurred in 48.3% of participants. One participant discontinued semzuvolimab because of a rash. Some participants had increases in eosinophils, which are a type of disease-fighting white blood cell, and some participants had elevated liver enzyme levels.^7,16

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

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

More information about semzuvolimab-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.

References

1. National Center for Biotechnology Information. PubChem substance record for SID 472420724, semzuvolimab, Source: FDA Global Substance Registration System (GSRS). Accessed October 5, 2023
2. United BioPharma. A randomized, double-blind, placebo-controlled Phase 3 trial with UB-421 in combination with optimized background regimen in patients with multi-drug resistant HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 22, 2020. NLM Identifier: NCT04406727. Accessed October 5, 2023
3. Jefferys R. The antiretroviral therapy pipeline 2023. Treatment Action Group Pipeline Report 2023. Accessed October 5, 2023
4. United BioPharma website. Pipeline. Accessed October 5, 2023
5. United Biomedical. A Phase IIa, open-label, multiple-dose trial to investigate the safety and efficacy of the UB-421 in asymptomatic HIV-1 infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 1, 2012. NLM Identifier: NCT01668043. Accessed October 5, 2023
6. United BioPharma. A Phase II, open-label, multiple-dose trial to investigate the safety and efficacy of UB-421 monotherapy in substitution for stable antiretroviral therapy in HIV infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 5, 2015. NLM Identifier: NCT02369146. Accessed October 5, 2023
7. Wang CY, Wong WW, Tsai HC, et al. Effect of anti-CD4 antibody UB-421 on HIV-1 rebound after treatment interruption. N Engl J Med. 2019;380(16):1535-1545. doi:10.1056/NEJMoa1802264. Accessed October 5, 2023
8. United BioPharma. The HIV functional cure potential of UB-421: a Phase II, randomized, open-label, controlled, 48 week, proof of concept study, to evaluate the safety of UB-421 in combination with standard antiretroviral therapy (ART) and the efficacy of HIV reservoir reduction as compared with ART alone in ART stabilized HIV-1 patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 12, 2018. NLM Identifier: NCT03743376. Accessed October 5, 2023
9. United BioPharma. A multicenter, single-arm, 24-week study of UB-421 in combination with optimized background therapy (OBT) regimen in patients with multi-drug resistant (MDR) HIV-1 infection.  In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 21, 2017. NLM Identifier: NCT03164447. Accessed October 5, 2023
10. 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 October 5, 2023
11. UBP Greater China (Shanghai) Co., Ltd. The HIV functional cure potential of UB-421: a Phase II, randomized, open-label, controlled, 48 week, proof of concept study, to evaluate the safety of UB-421 in combination with standard antiretroviral therapy (ART) and the efficacy of HIV reservoir reduction as compared with ART alone in ART stabilized HIV-1 patients.  In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 21, 2020. NLM Identifier: NCT04404049. Accessed October 5, 2023
12. United BioPharma. A Phase II proof-of-concept trial to evaluate the safety and efficacy of UB-421 plus chidamide 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 October 5, 2023
13. National Institute of Allergy and Infectious Diseases (NIAID). A single arm open label Phase 2 trial of anti-CD4 antibody UB-421 in combination with optimized background antiretroviral therapy in patients with multi-drug resistant HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 14, 2022. NLM Identifier: NCT05582694. Accessed October 5, 2023
14. United BioPharma. A Phase I, open-label, multi-dose study for evaluation of the safety, pharmacokinetics, and antiviral activity of UB-421 subcutaneous formulation administered in HIV-1 infected treatment naive patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 22, 2020. NLM Identifier: NCT04620304. Accessed October 5, 2023
15. United BioPharma. A Phase I, open-label, multi-dose study for evaluation of the safety, pharmacokinetics, and antiviral activity of UB-421 subcutaneous formulation in HIV infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 28, 2020. NLM Identifier: NCT04620291. Accessed October 5, 2023
16. Wang CY, Wong WW, Tsai HC, Chen YH, Liao MJ, Lynn S. A Phase 2 open-label trial of antibody UB-421 monotherapy as a substitute for HAART. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, WA. Poster 450LB. Accessed October 5, 2023