Drug information

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Other Names
GS-5423, 3BNC117-LS, 3BNC117-LS-J, (long-acting forms of 3BNC117)
Drug Class
Broadly Neutralizing Antibodies
Registry Number
1412902-17-0 (CAS)
Organization
Rockefeller University, Gilead Sciences
Phase of Development

3BNC117 is in Phase 2 development as a broadly neutralizing antibody for HIV treatment. (3BNC117 is also being developed for HIV prevention.)

(Compound details obtained from ChemIDplus Advanced,1 Nature article,2 Treatment Action Group website,Gilead Sciences press release,4 and Treatment Action Group Pipeline Report 20215)

 
What is 3BNC117?What is 3BNC117?

What is 3BNC117?

3BNC117 is an investigational drug that is being studied as a possible strategy to treat people living with HIV. 3BNC117 belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).3

A long-acting form of 3BNC117, called 3BNC117-LS (also known as GS-5423), is also under study for HIV treatment.3,6

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.7,8

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.8–10

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.9,11

Researchers are also trying to find out if 3BNC117 can prevent HIV infection in people who do not have the virus.5 This record focuses on the study of 3BNC117 as a treatment for HIV.

Select clinical trials of 3BNC117Select clinical trials of 3BNC117

Select clinical trials of 3BNC117

Study Name: NCT02588586
Phase: 2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety of 3BNC117 and its ability to delay or prevent viral rebound during an analytical treatment interruption of ART.12


Study Name: NCT02446847
Phase: 2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety and drug properties of 3BNC117. The study also examined how well 3BNC117 could delay or prevent viral rebound during an analytical treatment interruption of ART. 
Selected Study Results: Results published in the Nature (2016) journal showed that 3BNC117 was safe and well tolerated. 3BNC117 was effective in delaying viral rebound following an analytical treatment interruption of ART.2,13


Study Names: ROADMAP; NCT02850016
Phase: 2a
Status: This study has been completed.
Locations: Denmark, Germany, United States
Purpose: The purpose of this study was to compare the efficacy of the latency-reversing agent romidepsin plus 3BNC117 to the efficacy of romidepsin alone on delaying or preventing viral rebound during an analytical treatment interruption of ART.14,15 
Selected Study Results: Results published in The Lancet Microbe (2022) showed that romidepsin plus 3BNC117 and romidepsin given alone had no substantial effect on reducing latent HIV reservoir size in participants with viral suppression on ART. Additionally, romidepsin plus 3BNC117, compared to romidepsin given alone, was not effective in delaying the time to viral rebound during analytical treatment interruption. The observed time to viral rebound was not clinically meaningful in either group.15


Study Names: eCLEAR; NCT03041012
Phase: 1b/2a
Status: This study is ongoing, but not recruiting participants. 
Locations: Denmark and United Kingdom
Purpose: The purpose of this study is to evaluate whether the early administration of romidepsin and/or 3BNC117 in people who have never taken ART and are starting ART can reduce the time to viral suppression, limit the size of the latent HIV reservoir, and delay the time to viral rebound during an analytical treatment interruption of ART.16
Selected Study Results: Results presented at CROI 2022 showed that 3BNC117 given to participants initiating ART led to faster viral load decline and significantly reduced the number of infected cells, as compared to what was seen in participants receiving ART only. After one year, latent HIV reservoir size was reduced from baseline in all treatment groups, with the greatest reduction seen in people receiving 3BNC117 plus ART. Among participants who received 3BNC117 and had 3BNC117-sensitive virus, 80% maintained viral control during treatment interruption of ART. In contrast, among participants who had 3BNC117-resistant virus or did not receive 3BNC117, only 20% maintained viral control during treatment interruption.17


Study Names: TITAN; NCT03837756
Phase: 2a
Status: This study is currently recruiting participants.
Locations: Australia, Denmark, Norway, United States
Purpose: The purpose of this study is to evaluate the safety and effectiveness of lefitolimod and the bNAbs 3BNC117 and 10-1074 in delaying the time to re-initiate ART during an analytical treatment interruption of ART.18


Study Name: NCT03719664
Phase: 2
Status: This study is currently recruiting participants.
Location: United States
Purpose: The purpose of this study is to determine the most effective dose of 3BNC117 and the investigational fusion inhibitor albuvirtide and evaluate the safety and effectiveness of this combination as long-acting maintenance treatment.19


Study Names: RIO; NCT04319367
Phase: 2
Status: This study is currently recruiting participants.
Location: United Kingdom
Purpose: The purpose of this study is to determine whether the combination of the two long-acting bNAbs 3BNC117-LS and 10-1074-LS can prevent viral rebound after an analytical treatment interruption of ART.20


Study Name: NCT04819347
Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Location: China
Purpose: The purpose of this study is to evaluate the safety of combination therapy with albuvirtide plus 3BNC117 and assess whether this combination can prevent viral rebound following an analytical treatment interruption of ART.21


Study Name: NCT04560569
Phase: 2
Status: This study is currently recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the safety and efficacy of combination therapy with albuvirtide plus 3BNC117 in people who have multidrug-resistant HIV.22
 

Additional studies evaluating 3BNC117 for HIV treatment have been or are being conducted, including the following early-phase trials of 3BNC117 and 10-1074:

  • NCT03526848: A Phase 1 study that is assessing whether 3BNC117 and 10-1074 can prevent viral rebound in adults with HIV during an analytical treatment interruption of ART. This study is ongoing, but not recruiting participants.23
  • NCT03571204: A Phase 1 study that evaluated whether 3BNC117 and 10-1074 can control viral load levels in individuals with HIV who are currently not taking HIV medicines and in individuals with HIV who stop taking HIV medicines during an analytical treatment interruption. This study has been completed.24
  • NCT03554408: A Phase 1 study that investigated the safety and pharmacokinetics of 10-1074-LS when given alone and when given in combination with 3BNC117-LS in adults with and without HIV. This study has been completed.25
  • BEAT-2 (NCT03588715): A Phase 1 study evaluating whether the immune modulator peginterferon alfa-2b and 3BNC117 and 10-1074 can control viral rebound and reduce the latent HIV reservoir in adults with HIV during an analytical treatment interruption of ART. This study is ongoing, but not recruiting participants.26
  • NCT04250636: A Phase 1 study that will evaluate the safety, pharmacokinetics, and antiviral activity of single infusions of both 3BNC117-LS and 10-1074-LS in adults with HIV who are off ART. This study has been completed.27
  • NCT04811040: A Phase 1b study evaluating the safety and efficacy of 3BNC117-LS  (GS-5423) and 10-1074-LS (GS-2872) in combination with the investigational capsid inhibitor lenacapavir in controlling viral load levels in adults with HIV and viral suppression. This study is ongoing, but not recruiting participants.6

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

What side effects might 3BNC117 cause?What side effects might 3BNC117 cause?

What side effects might 3BNC117 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 3BNC117 listed above. 

NCT02446847:
In this study, most side effects were temporary and mild. Some participants experienced modest drops in their CD4 counts during the study, but most had their counts return to baseline levels by Week 12.2

ROADMAP (NCT02850016):
In the ROADMAP trial, most of the side effects reported during the study were mild. About 27% of the side effects that occurred were at least possibly related to romidepsin or 3BNC117. The most common side effects were nausea, headache, fatigue, general discomfort, chills, and vomiting.14,28,29

eCLEAR (NCT03041012):
In the Phase 1b/2a eCLEAR study, 60 participants were enrolled to receive ART only; ART plus 3BNC117; ART plus romidepsin; or a combination of ART, 3BNC117, and romidepsin. The majority of side effects that occurred during the trial were mild and unrelated to study treatment.17

Because 3BNC117 is still being studied, information on possible side effects of the drug is not complete. As testing of 3BNC117 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying 3BNC117?Where can I get more information about clinical trials studying 3BNC117?

Where can I get more information about clinical trials studying 3BNC117?

More information about 3BNC117-related research studies is available from ClinicalTrials.gov.

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. United States National Library of Medicine. ChemIDplus Advanced: 3BNC117. https://chem.nlm.nih.gov/chemidplus/rn/1412902-17-0. Accessed April 25, 2022
  2. Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535(7613):556-560.
  3. Treatment Action Group website. Research toward a cure trials. https://www.treatmentactiongroup.org/cure/trials/. Accessed April 25, 2022
  4. Gilead Sciences: press release, dated January 9, 2020. Gilead Sciences licenses portfolio of HIV antibodies from The Rockefeller University. https://www.gilead.com/news-and-press/press-room/press-releases/2020/1/gilead-sciences-licenses-portfolio-of-hiv-antibodies-from-the-rockefeller-university. Accessed April 25, 2022
  5. Jefferys R. HIV vaccines & passive immunization. Treatment Action Group Pipeline Report 2021. https://www.treatmentactiongroup.org/wp-content/uploads/2021/07/pipeline_2021_HIV_vaccine_final.pdf. Accessed April 25, 2022
  6. Gilead Sciences. A Phase 1b randomized, blinded, proof-of-concept study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with capsid inhibitor lenacapavir (GS-6207) in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 19, 2021. NLM Identifier: NCT04811040. https://clinicaltrials.gov/ct2/show/NCT04811040. Accessed April 25, 2022
  7. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. https://www.avac.org/blog/rise-broadly-neutralizing-antibodies. Accessed April 25, 2022
  8. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. https://www.hvtn.org/hiv-study-basics/key-hiv-vaccine-topics/using-antibodies-for-hiv-prevention.html. Accessed April 25, 2022
  9. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. https://www.niaid.nih.gov/diseases-conditions/sustained-art-free-hiv-remission. Accessed April 25, 2022
  10. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. https://www.niaid.nih.gov/diseases-conditions/future-hiv-treatment. Accessed April 25, 2022
  11. Grobben M, Stuart RA, van Gils MJ. The potential of engineered antibodies for HIV-1 therapy and cure. Curr Opin Virol. 2019;38:70-80. doi:10.1016/j.coviro.2019.07.007
  12. Rockefeller University. An open label, Phase 2 study of the safety and antiretroviral activity of 3BNC117 in HIV-infected individuals on combination antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 26, 2015. NLM Identifier: NCT02588586. https://clinicaltrials.gov/ct2/show/NCT02588586. Accessed April 25, 2022
  13. Rockefeller University. A Phase 2, open label study of the safety, antiretroviral activity and pharmacokinetics of 3BNC117 during a short analytical treatment interruption in HIV-infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US).  Registered on March 17, 2015. NLM Identifier: NCT02446847. https://clinicaltrials.gov/ct2/show/NCT02446847. Accessed April 25, 2022
  14. Rockefeller University. A Phase 2a, randomized study of romidepsin with or without 3BNC117 to evaluate the effects on the HIV-1 reservoir (ROADMAP). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2016. NLM Identifier: NCT02850016. https://clinicaltrials.gov/ct2/show/NCT02850016. Accessed April 25, 2022
  15. Gruell H, Gunst JD, Cohen YZ, et al. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial. Lancet Microbe. 2022;3(3):e203-e214. doi:10.1016/S2666-5247(21)00239-1
  16. Aarhus University Hospital. Early administration of latency reversing therapy and broadly neutralizing antibodies to limit the establishment of the HIV-1 reservoir during initiation of antiretroviral treatment - a randomized controlled trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 20, 2017. NLM Identifier: NCT03041012. https://clinicaltrials.gov/ct2/show/NCT03041012. Accessed April 25, 2022
  17. Gunst JD, Pahus MH, Rosás-Umbert M, et al. The impact of 3BNC117 and romidepsin treatment at ART initiation on HIV-1 persistence. Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2022. https://www.natap.org/2022/CROI/croi_54.htm. Accessed April 25, 2022
  18. University of Aarhus. Combining a TLR9 agonist with broadly neutralizing antibodies for reservoir reduction and immunological control of HIV infection: an investigator-initiated randomized, placebo-controlled, Phase IIa trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 7, 2019. NLM Identifier: NCT03837756. https://clinicaltrials.gov/ct2/show/NCT03837756. Accessed April 25, 2022
  19. Frontier Biotechnologies Inc. A Phase 2, multicenter, three-part study to establish the dosage, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 as long-acting maintenance therapy in virologically suppressed subjects with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 22, 2018. NLM Identifier: NCT03719664. https://clinicaltrials.gov/ct2/show/NCT03719664. Accessed April 25, 2022
  20. Imperial College London. A randomised placebo controlled trial of ART plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo in treated primary HIV infection on viral control off ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 2, 2020. NLM Identifier: NCT04319367. https://clinicaltrials.gov/ct2/show/NCT04319367. Accessed April 25, 2022
  21. Frontier Biotechnologies Inc. The Phase 2, two arms, one site, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 in virologically suppressed subjects with HIV-1 infection after analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 22, 2021. NLM Identifier: NCT04819347. https://clinicaltrials.gov/ct2/show/NCT04819347. Accessed April 25, 2022
  22. Frontier Biotechnologies Inc. A multicenter, two-arm, 24-week study of albuvirtide in combination with 3BNC117 in patients with multi-drug resistant (MDR) HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 17, 2020. NLM Identifier: NCT04560569. https://clinicaltrials.gov/ct2/show/study/NCT04560569. Accessed April 25, 2022
  23. Rockefeller University. An open label, randomized study of the safety and antiretroviral activity of 3BNC117 and 10-1074 in HIV-infected individuals on combination antiretroviral therapy and during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 3, 2018. NLM Identifier: NCT03526848. https://clinicaltrials.gov/ct2/show/NCT03526848. Accessed April 25, 2022
  24. National Institute of Allergy and Infectious Diseases (NIAID). An exploratory study of combination therapy with 3BNC117 and 10-1074 in HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US).  Registered on June 22, 2018. NLM Identifier: NCT03571204. https://clinicaltrials.gov/ct2/show/NCT03571204. Accessed April 25, 2022
  25. Rockefeller University. A Phase 1, dose escalation, first-in-human study of the safety and pharmacokinetics of the subcutaneous and intravenous administration of 10-1074-LS alone and in combination with 3BNC117-LS in HIV-infected and HIV-uninfected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 31, 2018. NLM Identifier: NCT03554408. https://clinicaltrials.gov/ct2/show/NCT03554408. Accessed April 25, 2022
  26. Luis Montaner. Pilot study on innate activation and viral control in HIV-infected adults undergoing an analytical treatment interruption after administration of pegylated interferon alpha 2b with broadly HIV-1 neutralizing antibodies (3BNC117, 10-1074). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 30, 2018. NLM Identifier: NCT03588715. https://clinicaltrials.gov/ct2/show/NCT03588715. Accessed April 25, 2022
  27. Rockefeller University. An open label, single arm study of the safety, pharmacokinetics and antiretroviral activity of the combination of 3BNC117-LS and 10-1074-LS in viremic HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2020. NLM Identifier: NCT04250636. https://clinicaltrials.gov/ct2/show/NCT04250636. Accessed April 25, 2022
  28. Gruell H, Cohen YZ, Gunst JD, et al. A randomized trial of the impact of 3BNC117 and romidepsin on the HIV-1 reservoir. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 8-11, 2020; Boston, MA. Abstract 38. https://www.croiconference.org/abstract/a-randomized-trial-of-the-impact-of-3bnc117-and-romidepsin-on-the-hiv-1-reservoir/. Accessed April 25, 2022
  29. Søgaard OS. A randomized trial of the impact of 3BNC117 and romidepsin on the HIV-1 reservoir. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 8-11, 2020; Boston, MA. http://www.croiwebcasts.org/console/player/44589?mediaType=slideVideo&. Accessed April 25, 2022
 

Last Reviewed: April 25, 2022