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
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).
- 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
- 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