bNAbs + N-803 for HIV/AIDS

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

28 Participants Needed

Trial Summary

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.

What makes the drug bNAbs + N-803 unique for treating HIV/AIDS?

The drug bNAbs + N-803 is unique because it combines broadly neutralizing antibodies (bNAbs) with N-803, an IL-15 superagonist that boosts immune cells like CD8+ T cells and natural killer cells, potentially reducing HIV reservoirs by activating latent virus and enhancing immune response, which is different from standard antiretroviral therapy that only suppresses viral replication. ^{1 2 3 4 5}

What is the purpose of this trial?

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 broadly neutralizing antibodies, 3BNC117-LS dosed once at 30 mg/kg and 10-1074-LS dosed once at 10 mg/kg, both intravenously (IV) at week 0, plus an IL-15 superagonist complex, N-803, dosed at 6 mcg/kg, subcutaneously (SC) at week 1 and then every 3 weeks for a total of 8 doses, in ART-treated adults living with HIV during analytical treatment interruption.

Research Team

Marina Caskey, MD

Principal Investigator

The Rockefeller University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2022]

2. United States 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques. [2020]