NCT04808908

Effect of N-803 on B Cell Follicles in Antiretroviral Treated HIV Disease

Completed Phase 1 Results posted Last updated 2 April 2024

What this trial tests

Phase 1 trial testing N-803 in Hiv in 10 participants. Completed in 1 January 2023.

Timeline

1 April 2021

Primary endpoint
18 July 2022

1 January 2023

Quick facts

Lead sponsor	University of Minnesota
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	1 April 2021
Primary completion	18 July 2022
Estimated completion	1 January 2023
Sites	2 locations across United States

Drugs / interventions tested

• N-803 — full drug profile →

Conditions studied

• Hiv — all drugs for Hiv →
• HIV Infections — all drugs for HIV Infections →
• AIDS — all drugs for AIDS →

Sponsor

University of Minnesota

Who can join

Adults 18 to 65, any sex, with Hiv or HIV Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety (Adverse Event Rate) Primary · 6 months

Safety is a primary outcome of this phase 1b trial. Safety will be reported as the number of adverse events per participant. This includes all adverse events (total regardless of severity)

Group	Value	95% CI
N-803	20	± 6.2

Frequency of CD8+ T Cells in Follicles Secondary · 6 months

Frequency of CD8+ T cells in B cell follicles will be determined using flow cytometry and reported in units of cells/g tissue

Group	Value	95% CI
N-803	29400	± 26900

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

N-803

Serious: 0/10 (0%)

Deaths: 0/10

Other adverse events (8 terms — click to expand)

Reaction	System	N-803
Injection site erythema	General disorders	—
Myalgia	General disorders	—
Fatigue or malaise	General disorders	—
Headache	General disorders	—
pain	General disorders	—
lymphadenopathy	Blood and lymphatic system disorders	—
fever	General disorders	—
Injection site induration	General disorders	—

Data from ClinicalTrials.gov NCT04808908 adverse events section.

Sponsor's own description

N-803 has demonstrated ability to reactivate HIV from latency and can activate T cells and NK cells to clear those cells, thus reducing the reservoir. However, a concern is that CD8 T cells may be excluded from the B cell follicles, where a significant part of the reservoir resides. Webb, et al, has shown that in SIV infected monkeys CD8 T cells in follicles increase in frequency when N-803 is administered. We hypothesize that in HIV infected humans treated with N-803 that CD8 T cells will increase in B cell follicles and that there will be a further reduction in the frequency of cells with an inducible provirus.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. The application of Interleukin-2 family cytokines in tumor immunotherapy research.
   Zhou Y, Quan G, Liu Y, Shi N, et al · · 2023 · cited 32× · PMID 36936961 · DOI 10.3389/fimmu.2023.1090311
2. The HIV Latency Reversal Agent HODHBt Enhances NK Cell Effector and Memory-Like Functions by Increasing Interleukin-15-Mediated STAT Activation.
   Macedo AB, Levinger C, Nguyen BN, Richard J, et al · · 2022 · cited 20× · PMID 35867565 · DOI 10.1128/jvi.00372-22
3. Multimeric immunotherapeutic complexes activating natural killer cells towards HIV-1 cure.
   Schober R, Brandus B, Laeremans T, Iserentant G, et al · · 2023 · cited 9× · PMID 37936122 · DOI 10.1186/s12967-023-04669-4
4. Immunomodulation with IL-7 and IL-15 in HIV-1 infection.
   Gunst JD, Goonetilleke N, Rasmussen TA, Søgaard OS. · · 2023 · cited 5× · PMID 37767312 · DOI 10.1016/j.jve.2023.100347
5. Advances in host-directed therapy for tuberculosis and HIV coinfection: enhancing immune responses.
   Prasanna P, Herrera B, Schlesinger LS, Paiardini M, et al · · 2025 · cited 3× · PMID 40345900 · DOI 10.1016/j.tim.2025.04.006
6. Impact of the IL-15 superagonist N-803 on lymphatic reservoirs of HIV.
   Rhein J, Chipman JG, Beilman GJ, Cromarty R, et al · · 2025 · cited 1× · PMID 40471871 · DOI 10.1172/jci.insight.190831