What is PGDM1400? What is PGDM1400?

What is PGDM1400?

PDGM1400 is an investigational drug that is being studied as a possible strategy to treat people with HIV. PDGM1400 belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).¹

A long-acting form of PGDM1400, called PGDM1400LS, is also under study for HIV treatment and/or prevention.^1,3

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 broadly neutralizing antibodies work? How do broadly neutralizing antibodies work?

How do broadly neutralizing antibodies work?

Antibodies are proteins that the immune system makes to fight infection. A person with HIV produces specific antibodies against HIV. However, most of these antibodies do not stop HIV from multiplying in the body.^4,5

Some people with HIV naturally produce rare types of HIV antibodies called broadly neutralizing antibodies (bNAbs). bNAbs are powerful antibodies that can work against different HIV strains. bNAbs can block HIV from entering healthy cells and activate other immune cells to help destroy infected cells.^4,6,7

Researchers are investigating whether giving bNAbs to people with HIV can help them maintain undetectable levels of HIV without the need for daily antiretroviral therapy. Additionally, some bNAbs are being studied because they may be able to reduce the size of the latent HIV reservoir.^6,8

Researchers are also trying to find out if giving bNAbs to people who do not have HIV can help protect them from getting the virus.³ This record focuses on the study of PGDM1400 as a treatment for HIV.

Select clinical trials of PGDM1400 Select clinical trials of PGDM1400

Select clinical trials of PGDM1400

Study Names: IAVI T003; NCT03721510

Phase: 1/2a 
Status: This study has been completed. 
Location: United States
Purpose: The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the bNAbs PGT121, VRC07-523LS, and PGDM1400 in adults with and without HIV.⁹ 
Selected Study Results: Results presented at CROI 2024 showed that triple bNAb therapy with PGT121, VRC07-523LS, and PGDM1400 was generally safe and well tolerated. Most participants (83%) who received bNAb therapy while undergoing an analytical treatment interruption of antiretroviral therapy (ART) maintained viral suppression for at least 28 weeks. Although bNAb concentrations declined to low or undetectable levels during the follow-up period, 36% of the participants who completed follow-up had viral suppression through the end of the study (Week 44).¹⁰

Study Name: NCT04983030

Phase: 1/2a
Status: This study is currently recruiting participants. 
Location: United States
Purpose: The purpose of this study is to evaluate the safety, immunogenicity, and efficacy of therapeutic HIV vaccines in combination with bNAbs (PGT121, PGDM1400, and VRC07-523LS) in adults with viral suppression on ART. Researchers will assess whether this combination strategy can control participants’ viral load levels during an analytical treatment interruption of ART.¹¹

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

Additional studies evaluating PGDM1400 for HIV treatment have been completed or are being conducted, including the following Phase 1 trials:

• IAVI T002 (NCT03205917): A study that evaluated the safety, tolerability, pharmacokinetics, and antiviral activity of the bNAbs PGDM1400, PGT121, and VRC07-523LS in adults without HIV and adults with HIV who were not on ART. This study has been completed, and results are available from CROI 2022 and Nature Medicine (2022).¹²
• RV 582 (NCT05769569): A study evaluating the safety and efficacy of VRC07-523LS, PGDM1400LS, and N-803 (an investigational therapy based on the cytokine IL-15) in combination with the therapeutic HIV vaccines for the induction of HIV remission. See the ClinicalTrials.gov record for this study’s status.¹³

What side effects might PGDM1400 cause? What side effects might PGDM1400 cause?

What side effects might PGDM1400 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 PGDM1400 listed above.

IAVI T003; NCT03721510

In this Phase 1/2a trial, PGT121, VRC07-523LS, and PGDM1400 infusions were reported to be generally safe and well tolerated. Four serious and/or severe side effects occurred during the study but all were considered unrelated to the study bNAbs.^9,10

Because PGDM1400 is still being studied, information on possible side effects of the drug is not complete. As testing of PGDM1400 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying PGDM1400? Where can I get more information about clinical trials studying PGDM1400?

Where can I get more information about clinical trials studying PGDM1400?

More information about PGDM1400-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 References

References

1. Treatment Action Group website. Research toward a cure trials. Accessed April 23, 2024
2. HIV Vaccine Trials Network and HIV Prevention Trials Network. Protocol HVTN 143/HPTN 109: a phase 1 clinical trial to evaluate the safety, tolerability, and pharmacokinetics of monoclonal antibodies VRC01.23LS, PGT121.414.LS and PGDM1400LS administered via intravenous infusion in adults without HIV [Version 1.0]; June 7, 2023. Accessed April 23, 2024
3. Jefferys R. HIV vaccines & passive immunization. Treatment Action Group Pipeline Report 2023. Accessed April 23, 2024
4. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed April 23, 2024
5. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed April 23, 2024
6. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed April 23, 2024
7. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed April 23, 2024
8. Grobben M, Stuart RA, van Gils MJ. The potential of engineered antibodies for HIV-1 therapy and cure. Current Opinion in Virology. 2019;38:70-80. doi:10.1016/j.coviro.2019.07.007. Accessed April 23, 2024
9. International AIDS Vaccine Initiative. A Phase 1/2a open label study of the safety, tolerability, pharmacokinetics and antiviral activity of PGT121, VRC07-523LS and PGDM1400 monoclonal antibodies in HIV-uninfected and HIV-infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 16, 2018. NLM Identifier: NCT03721510. Accessed April 23, 2024
10. Juelg BD, Walker-Sperling VE, Wagh K, et al. Therapeutic efficacy of a triple combination of HIV-1 broadly neutralizing antibodies. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Accessed April 23, 2024
11. Boris Juelg, MD PhD. A safety, immunogenicity and efficacy Phase 1/2a study of a heterologous Ad26.Mos4.HIV, MVA-BN-HIV vaccine regimen plus broadly neutralizing antibodies PGT121, PGDM1400, and VRC07-523LS in HIV-1-infected adults on suppressive ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 5, 2021. NLM Identifier: NCT04983030. Accessed April 23, 2024
12. International AIDS Vaccine Initiative. A Phase 1 randomized placebo-controlled clinical trial of the safety, pharmacokinetics and antiviral activity of PGDM1400 and PGT121 and VRC07-523LS monoclonal antibodies in HIV-uninfected and HIV-infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 12, 2017. NLM Identifier: NCT03205917. Accessed April 23, 2024
13. Henry M. Jackson Foundation for the Advancement of Military Medicine. Safety and efficacy of broadly neutralizing antibodies followed by innate immune stimulation and therapeutic vaccination for the induction of HIV remission. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 15, 2023. NLM Identifier: NCT05769569. Accessed April 23, 2024

Last Reviewed: April 23, 2024