N-803 for HIV

(INTERRUPT-HIV Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Michael Peluso, MD

Must be taking: Antiretrovirals

Must not be taking: Long-acting ART

Disqualifiers: Hepatitis B, Hepatitis C, AIDS, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called N-803 (Interleukin-15) to determine if it can help people with HIV control the virus without regular medication. HIV often hides in the body, making complete elimination difficult. N-803 aims to boost the immune system to target this hidden virus. The trial includes two groups: one receiving N-803 and another receiving a placebo, with all participants eventually receiving the active drug. People with HIV who have been on stable medication (ART) for at least six months and are willing to pause their treatment may be eligible to join. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Participants will need to stop their current HIV medications temporarily as part of the study, which involves a planned break from treatment.

Is there any evidence suggesting that N-803 is likely to be safe for humans?

Research has shown that N-803, also known as Interleukin-15, is generally safe for people with HIV who are on antiretroviral therapy (ART). One study found that most participants did not experience serious side effects, indicating it was well-tolerated. Another study suggests that N-803 might help reduce the amount of HIV hiding in the body by boosting immune cells that fight infections.

The FDA has already approved N-803 for treating bladder cancer, which provides some confidence in its safety. However, since it is being tested for HIV, further research is needed to confirm its safety for this use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Unlike the standard HIV treatments that primarily focus on managing viral load with antiretroviral therapy, N-803 offers a fresh approach by utilizing Interleukin-15. This unique mechanism amplifies the body's immune response, potentially enhancing the ability to control the virus without continuous medication. Researchers are excited because N-803 might help the immune system target and eliminate latent HIV reservoirs, a significant hurdle that current treatments can't fully address.

What evidence suggests that N-803 might be an effective treatment for HIV?

Research has shown that N-803, also known as Interleukin-15, might help control HIV by activating the hidden virus inside immune cells. This trial will evaluate N-803, which boosts the activity of important immune cells like CD8+ T cells and natural killer (NK) cells, helping to clear out infected cells. Studies have found that N-803 can wake up hidden HIV and strengthen immune responses, potentially reducing the virus in the body. Early trials using N-803 with NK cells showed promise in lowering the amount of virus in people with HIV. Additionally, N-803 has improved immune cell functions, which might lead to a smaller amount of the virus remaining in the body. These findings suggest that N-803 could play a key role in new HIV treatment strategies. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with HIV/AIDS. Participants must have a stable regimen of antiretroviral therapy (ART), maintain an undetectable viral load, and meet specific immune cell count criteria. People cannot join if they have other significant health issues, are pregnant or breastfeeding, or use certain medications that could interfere with the study.

Inclusion Criteria

Plasma HIV RNA levels less than 200 copies/mL at each determination in the previous 6 months

I am willing to temporarily stop my ART for the study.

Screening CD4+ T-cell count ≥ 350 cells/mm3

Exclusion Criteria

I am on an ART regimen with a NNRTI and cannot switch.

Screening platelets < 125,000/mm3

My hemoglobin level is below the normal range for my gender.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase A (Blinded)

Participants receive either N-803 or placebo during the blinded portion of the trial

7 days

1 visit (in-person)

Treatment Phase B (Open-label)

Participants receive the active study drug N-803 during the open-label portion of the trial

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-803 (Interleukin-15)

Trial Overview The study is testing N-803, also known as Interleukin-15 or IL-15. It's designed to stimulate the immune system to potentially control HIV without ongoing medication by targeting the virus hidden in immune cells. Some participants will receive N-803 while others will get a saline placebo for comparison.

How Is the Trial Designed?

Group I: N-803 Experimental Treatment 1 Intervention

Participants in this arm will receive the active study drug during the blinded portion (Phase A) of the trial. They will receive the active study drug during the open-label portion (Phase B) of the trial.

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive placebo during the blinded portion (Phase A) of the trial. They will receive the active study drug during the open-label portion (Phase B) of the trial.

Who Is Running the Clinical Trial?

Michael Peluso, MD

Lead Sponsor

Trials

1

Recruited

40+

amfAR, The Foundation for AIDS Research

Collaborator

Trials

29

Recruited

6,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10537516/

IL-15 and N-803 for HIV Cure Approaches - PMC They have been shown to reactivate latent HIV and enhance immune effector function, both of which are potentially required for effective reduction of latent ...

2. insight.jci.org insight.jci.org/articles/view/190831

Impact of the IL-15 superagonist N-803 on lymphatic ... Our findings suggest N-803 may reduce the HIV reservoir in LTs of PWH on ART, an effect likely mediated by enhanced NK cell function.

3. immunitybio.com immunitybio.com/n-803-combined-with-natural-killer-cells-showed-potential-to-reduce-hiv-viral-load-in-hiv-positive-subjects-part-of-hiv-cure-study/

HIV Cure Study: N-803 with Natural Killer Cells May ... Data from a Phase 1 pilot study showed N-803 combined with natural killer cells could have the potential to reduce viral load in people living with HIV.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04340596

Safety, Tolerability, and Efficacy of IL-15 Superagonist (N- ... This study will evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40471871/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1J1_5BOh1PfuJCilZcff_MgF0HGgpL9y2eFYBseob273NyXUj-&fc=20250120142857&ff=20250605200002&v=2.18.0.post9+e462414

Impact of the IL-15 superagonist N-803 on lymphatic ... The IL-15 superagonist N-803 has been shown to enhance NK and T cell function and thus may reduce viral reservoirs.METHODSTo determine the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35102335/

Safety and virologic impact of the IL-15 superagonist N-803 ... These data suggest that N-803 administration in ART-suppressed people living with HIV is safe and that larger clinical trials are needed to further investigate ...

7. immunitybio.com immunitybio.com/niaid-sponsored-study-shows-n-803-combined-with-neutralizing-antibodies-could-lead-to-sustained-hiv-viral-control-after-discontinuation-of-antiretroviral-therapy/

Study: N-803 with Antibodies Might Sustain HIV Control ... Using N-803, in combination with broadly neutralizing antibodies (bNAbs), led to sustained viral control after discontinuation of antiretroviral therapy (ART).

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38207119/

Safety and Virologic Impact of Haploidentical NK Cells Plus ... We hypothesized that an infusion of NK cells, supported by interleukin 2 (IL-2) or IL-15, could decrease virus-producing cells in the lymphatic tissues.