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

About

Brief Summary

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).

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

65 Years

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