A Phase I Clinical Trial of the Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

ACTG A5386

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).

2021-05-21

2025-10-31

2026-04-30

Recruiting

Early phase I

46

Inclusion Criteria * HIV-1 infection * On ART for at least 96 weeks prior to randomization * On ART regimen containing an integrase inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) or dolutegravir/lamivudine for at least 6 weeks prior to randomization. * CD4 cell count \>450 cells/mm\^3 within 90 days prior to randomization * CD4 cell count nadir ≥200 cells/mm\^3. * Plasma HIV-1 RNA levels of \<50 copies/mL for at least 96 weeks prior to randomization * Select laboratory results within 90 days of randomization * IC90 to 10-1074 of ≤1.5 mcg/mL, 10-1074 maximum percent inhibition (MPI) ≥98%, and IC80 to VRC07-523LS of ≤1 mcg/mL on the Monogram PhenoSense assay. * QTcF interval ≤440 msec within 90 days prior to randomization. * For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 30 days prior to randomization * Cisgender women and transgender men of reproductive potential must agree to use two methods of contraception, if participating in sexual activity that could lead to pregnancy. * Cisgender men and transgender women participants engaging in sexual activity that could lead to pregnancy and who are of reproductive potential must agree to use a barrier method of contraception * Willingness to abstain from sexual intercourse or use a barrier method of contraception consistently * Willingness to participate in an ATI. * Weight \>50 kg and \<115 kg. * Completion of pre-entry leukapheresis Exclusion Criteria * History of AIDS-defining illness, with the exception of recurrent pneumonia. * History of or current clinical cardiovascular disease * Current clinically significant acute or chronic medical condition * History of HIV-associated neurocognitive disease * History of an HIV-associated malignancy * ART initiated during acute HIV infection * Current receipt of ART other than NRTI and integrase inhibitor. * Resistance to one or more drugs in two or more ARV drug classes. * Receipt of any therapeutic HIV vaccine or monoclonal antibody therapy (anti-HIV or otherwise) at any time in the past. * History of prior immunoglobulin (IgG) therapy. * History of use of any immunomodulatory medications within 6 months prior to randomization * Participation in another clinical study of an investigational product currently or within past 12 weeks * Breastfeeding or pregnancy

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 46, 'type': 'ESTIMATED'}}

2024-04-15