bNAbs + N-803 for HIV/AIDS

Not currently recruiting at 2 trial locations

Overseen By Marina Caskey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rockefeller University

Must be taking: Antiretrovirals

Must not be taking: Corticosteroids, Chemotherapy

Disqualifiers: AIDS, ASCVD, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for adults with HIV who are already on antiretroviral therapy (ART). The study aims to determine if two special antibodies, 10-1074-LS (also known as Zinlirvimab or GS-2872) and 3BNC117-LS (also known as GS-5423 or Teropavimab), along with an immune-boosting drug, N-803 (also known as IL-15 Superagonist), can safely control the virus in the body. It targets individuals living with HIV who have maintained low virus levels with ART and have not experienced major treatment interruptions. Participants should have stable health conditions and agree to specific treatment and lifestyle guidelines. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

Yes, if you are on an NNRTI-based regimen, you will need to switch to an integrase inhibitor-based regimen for at least 4 weeks before stopping your current HIV medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Researchers are examining the safety of combining two long-acting antibodies, 3BNC117-LS and 10-1074-LS, with the drug IL-15 superagonist N-803 for people with HIV. Previous studies have shown that these antibodies are generally safe for humans. Most participants did not experience major side effects, though some reported mild reactions like redness at the injection site or minor flu-like symptoms.

The IL-15 superagonist N-803, when combined with these antibodies, is under investigation to help control HIV. While specific side effects are not detailed, similar trials have shown that N-803 can cause mild reactions at the injection site and temporary fever, which are manageable.

Overall, these treatments have demonstrated a promising safety record in early studies, but further research is needed to confirm these findings. This study is in the first phase, focusing primarily on safety assessment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of bNAbs (broadly neutralizing antibodies) like 3BNC117-LS and 10-1074-LS with N-803 for treating HIV/AIDS because it offers a new approach compared to standard antiretroviral therapies. Unlike current treatments, which mainly focus on suppressing the virus, these bNAbs can directly target and neutralize a wide range of HIV strains, potentially reducing the viral reservoir in the body. Additionally, N-803, an interleukin-15 superagonist, boosts the immune response by enhancing the proliferation of natural killer and T cells, which might help in controlling the virus without continuous daily medication. This combination could lead to longer-lasting viral suppression and possibly reduce the frequency of dosing, making it a promising alternative for people living with HIV.

What evidence suggests that this trial's treatments could be effective for HIV/AIDS?

In this trial, participants will receive a combination of 3BNC117-LS, 10-1074-LS, and N-803. Research has shown that 3BNC117-LS and 10-1074-LS are more effective against HIV than a placebo. These special antibodies are designed to stop the virus from infecting cells. Early studies suggest that adding N-803, a compound that boosts the immune system, may enhance this combination's effectiveness. Previous patients demonstrated promising results, indicating this approach could help control HIV without constant antiretroviral therapy. Overall, this combination aims to reduce the virus's ability to multiply while strengthening the body's natural defenses. ^{1 2 3 6 7}

Who Is on the Research Team?

Marina Caskey, MD

Principal Investigator

The Rockefeller University

Are You a Good Fit for This Trial?

Adults aged 18-70 with confirmed HIV-1 infection, on effective antiretroviral therapy for at least 48 weeks, and with a stable immune status. Participants must not have had significant interruptions in their HIV treatment, no recent malignancies or hepatitis B/C infections, and agree to use contraception.

Inclusion Criteria

Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms

At least two Viral Load (VL) measurements within 48 weeks prior to the Step 0 screening visit must be available for review

I am on HIV treatment with undetectable virus levels for at least 48 weeks.

Exclusion Criteria

QTcF interval ≥ 440 ms at screening

Participants with known hypersensitivity to any constituent of the investigational products

I started antiretroviral therapy soon after my infection was diagnosed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3BNC117-LS and 10-1074-LS intravenously at week 0, and N-803 subcutaneously starting at week 1 and then every 3 weeks for a total of 8 doses

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including ART interruption and potential viral rebound

48 weeks

Regular monitoring visits

Long-term follow-up

Participants are monitored for ART restart criteria and long-term safety and effectiveness

72 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 10-1074-LS
• 3BNC117-LS
• N803

Trial Overview The study is testing the combination of two long-acting antibodies (3BNC117-LS and 10-1074-LS) given intravenously once, plus an IL-15 superagonist complex (N-803) given subcutaneously every three weeks during a break from standard HIV treatments.

How Is the Trial Designed?

Group I: 3BNC117-LS + 10-1074-LS + N-803 Experimental Treatment 3 Interventions

3BNC117-LS dosed at 30 mg/kg IV, day 0 10-1074-LS dosed at 10 mg/kg IV, day 0 N-803 dosed at 6 mcg/kg, SC, 8 doses every 3 weeks (week 1 through week 22)

Who Is Running the Clinical Trial?

Rockefeller University

Lead Sponsor

Trials

162

Recruited

16,700+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Perelman School of Medicine University of Pennsylvania

Collaborator

Trials

3

Recruited

4,000+

Published Research Related to This Trial

N-803 enhances the immune response by increasing the function of CD8 T cells and NK cells, leading to a transient decline in plasma viremia in SIV+ rhesus macaques, particularly in those with low viral loads.

The effectiveness of N-803 is greater in SIV+ animals that can naturally control the virus, as it boosts the proliferation and killing capacity of SIV-specific immune cells more significantly in these 'controllers' compared to 'noncontrollers'.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of Simian Immunodeficiency Virus Infection in Prophylactically Vaccinated, Antiretroviral Treatment-Naive Macaques Is Required for the Most Efficacious CD8 T Cell Response during Treatment with the Interleukin-15 Superagonist N-803. Ellis-Connell, AL., Balgeman, AJ., Harwood, OE., et al.[2023]

IL-15 is a crucial cytokine that enhances T cell and NK cell responses against HIV/SIV, but its use can sometimes lead to unwanted immune activation and faster disease progression, highlighting the need for careful timing in treatment.

The IL-15 superagonist N-803 shows promise in improving immune responses against HIV/SIV by enhancing CD8+ T cell activity and potentially reversing viral latency, making it a valuable candidate for combination therapies with antiretroviral treatments and vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection. Harwood, O., O'Connor, S.[2022]

The phase 1 study of N-803, an IL-15 superagonist, demonstrated that it is safe and well-tolerated in 16 ART-suppressed individuals living with HIV, with the maximum tolerated dose identified as 6.0 mcg kg-1.

N-803 treatment led to increased activation of immune cells and a significant decrease in the frequency of cells with inducible HIV provirus, suggesting potential for reducing HIV reservoirs, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and virologic impact of the IL-15 superagonist N-803 in people living with HIV: a phase 1 trial. Miller, JS., Davis, ZB., Helgeson, E., et al.[2022]

The combination of N-803, an IL15 receptor superagonist, with rituximab was found to be safe and well tolerated in patients with relapsed/refractory non-Hodgkin lymphoma, leading to durable clinical responses even in those resistant to rituximab.

N-803 significantly enhanced the activation and expansion of natural killer (NK) cells and CD8+ T cells, indicating its potential to improve the effectiveness of tumor-targeting monoclonal antibodies in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma. Foltz, JA., Hess, BT., Bachanova, V., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05245292

NCT05245292 | 3BNC117-LS and 10-1074-LS Plus N-803 ... The proposed study is a phase 1, open label, single arm study to evaluate the safety and antiretroviral activity of the combination of two long-acting ...

2. reporter.nih.gov reporter.nih.gov/search/bYhowSCqjECsv9f-uFJVoQ/project-details/9804264

Immunologic control of HIV-1 through combination bNAbs ... This project aims to conduct two clinical studies to evaluate the antiviral activity of the combination of the long-acting (“LS”) variants of 3BNC117 and 10- ...

3. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/3bnc117/health-professional

3BNC117 Health Professional Drug Record | NIH Selected Study Results: Results presented at CROI 2025 showed that the combination of 3BNC117-LS and 10-1074-LS was significantly more effective than placebo in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12116831/

Future of bNAbs in HIV Treatment - PMC This review explores the potential role of bNAbs in HIV management, addressing their mechanisms of action, current limitations, and future directions.

5. immunitybio.com immunitybio.com/hiv/

HIV Vaccine Trials - Clinical Aids Research & Treatment The trial is enrolling 15 patients and is designed to investigate the safety, tolerability and immunostimulatory effects of administering N-803 ...

6. reporter.nih.gov reporter.nih.gov/search/6tRRNZot9ESjz_ldUD2cCQ/project-details/10754874

Immunologic control of HIV-1 through combination bNAbs ... This project aims to conduct two clinical studies to evaluate the antiviral activity of the combination of the long-acting (“LS”) variants of 3BNC117 and 10- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05729568

NCT05729568 | A Study of Teropavimab and Zinlirvimab in ... The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab ...