118 Participants Needed

IL-15 Superagonist + Antibodies for HIV/AIDS

Recruiting at 15 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Must be taking: Integrase inhibitors, NRTIs
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Will I have to stop taking my current medications?

The trial requires participants to be on a specific ART regimen with an integrase inhibitor and two NRTIs or dolutegravir/lamivudine. If you are on a different ART regimen, you may need to change your medications to meet this requirement.

What data supports the effectiveness of the drug IL-15 Superagonist + Antibodies for HIV/AIDS?

Research shows that the IL-15 superagonist N-803 can activate immune cells, like CD8+ T cells and natural killer cells, which are important for fighting HIV. In studies, N-803 has been shown to reduce the amount of virus in the body temporarily and enhance the immune response, suggesting potential benefits in managing HIV.12345

Is the IL-15 superagonist N-803 safe for humans?

In a phase 1 trial with people living with HIV, the IL-15 superagonist N-803 was generally safe, with the most common side effects being mild rash at the injection site and swollen lymph nodes. Some participants experienced minor changes in heart rhythm, but no serious lab-related side effects were linked to the drug.23456

How is the drug N-803 different from other HIV treatments?

N-803 is unique because it is an IL-15 superagonist that enhances the immune system's ability to fight HIV by boosting the activity of T cells and natural killer cells, potentially reducing the virus reservoir. Unlike standard antiretroviral therapy, which suppresses the virus, N-803 aims to activate latent virus and improve immune response, offering a novel approach to managing HIV.14567

Research Team

TW

Timothy Wilkin, MD, MPH

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults with HIV/AIDS who've been on ART including an integrase inhibitor and NRTIs or dolutegravir/lamivudine for at least 96 weeks, have a stable CD4 count, no history of AIDS-defining illness except recurrent pneumonia, and agree to use contraception. They must not be pregnant, breastfeeding, or have used immunomodulatory meds recently.

Inclusion Criteria

I am infected with HIV-1.
Select laboratory results within 90 days of randomization
CD4 cell count nadir ≥200 cells/mm^3
See 13 more

Exclusion Criteria

I have a history of heart disease.
I am currently on HIV treatment that is not NRTI or integrase inhibitor.
Breastfeeding or pregnancy
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 12 weeks
1 visit (in-person)

Treatment

Participants receive N-803 with or without combination bNAbs for HIV-1 control

52 weeks
Multiple visits (in-person) every 3 weeks

Analytic Treatment Interruption (ATI)

Participants interrupt antiretroviral therapy and are monitored closely

Up to 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

  • 10-1074
  • N-803
  • VRC07-523LS
Trial OverviewThe study tests the safety and effectiveness of N-803 (an IL-15 superagonist) alone or combined with bNAbs (VRC07-523LS & 10-1074) in controlling HIV without regular treatment. Participants will temporarily stop their usual ART to see if these new drugs can maintain low HIV levels.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B: N-803 in combination with 10-1074 and VRC07-523LSExperimental Treatment3 Interventions
Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows: * At Step 2 entry: * VRC07-523LS 20 mg/kg * 10-1074 30 mg/kg * At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses * At Step 2, week 9: 10-1074 30 mg/kg
Group II: Arm A: N-803 onlyExperimental Treatment1 Intervention
Participants will receive N-803 6 mcg/kg 1 week after Step 2 entry and then every 3 weeks for a total of eight doses.

N-803 is already approved in United States for the following indications:

🇺🇸
Approved in United States as N-803 for:
  • Non-muscle invasive bladder cancer (NMIBC) in combination with BCG

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials
3,361
Recruited
5,516,000+

Rockefeller University

Collaborator

Trials
162
Recruited
16,700+

ImmunityBio, Inc.

Industry Sponsor

Trials
75
Recruited
5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Findings from Research

ALT-803, an interleukin-15 superagonist, can boost the immune response by increasing CD8+ T and NK cell populations in SIV-positive rhesus macaques, leading to a temporary reduction in viral loads by about 2 logs during treatment cycles.
The study highlights that while ALT-803 shows promise as an immunomodulatory agent for controlling HIV/SIV replication, the effects are transient due to decreased T cell responsiveness and increased immunosuppressive T cells over time, suggesting the need for optimized treatment regimens.
ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment.Ellis-Connell, AL., Balgeman, AJ., Zarbock, KR., et al.[2020]
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'.
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.
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]

References

ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment. [2020]
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]
Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma. [2022]
Safety and virologic impact of the IL-15 superagonist N-803 in people living with HIV: a phase 1 trial. [2022]
Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection. [2022]
Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent. [2018]
In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice. [2018]