The proposed study is a phase 1, open label, single arm study to evaluate the safety and antiretroviral activity of the combination of two long-acting broadly neutralizing antibodies, 3BNC117-LS dosed once at 30 mg/kg and 10-1074-LS dosed once at 10 mg/kg, both intravenously (IV) at week 0, plus an IL-15 superagonist complex, N-803, dosed at 6 mcg/kg, subcutaneously (SC) at week 1 and then every 3 weeks for a total of 8 doses, in ART-treated adults living with HIV during analytical treatment interruption.
The proposed study is a phase 1, open label study of the safety and antiretroviral activity of the 3BNC117-LS plus 10-1074-LS broadly neutralizing antibody (bNAb) combination plus N-803, an IL-15 superagonist complex, in ART-treated individuals living with HIV during interruption of ART. Thirty-six eligible participants will be enrolled sequentially and will be assigned to Group A or Group B after Monogram PhenoSense Assay results become available: Group A - participants with 3BNC117 and 10-1074 IC90 less or equal to 1 mcg/mL and MPI greater or equal to 98% by the Monogram PhenoSense assay using PBMCs; Group B - all other participants, including participants from whom the PhenoSense Assay (PBMC) does not yield a result. Participants will discontinue ART on day 2 (2 days after the first antibody infusions) and will be followed for up to 72 weeks while off ART and for 12 weeks after ART is resumed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Intravenous infusion of 3BNC117-LS at 30 mg/kg
Intravenous infusion of 10-1074-LS at 10 mg/kg
Subcutaneous injections of N803 at 6 mcg/kg
Weill Cornell Medicine, Cornell Clinical Trials Unit
New York, New York, United States
The Rockefeller University
New York, New York, United States
Perelman School of Medicine University of Pennsylvania
Philadelphia, Pennsylvania, United States
Treatment-related Grade 3 adverse events and serious adverse events
The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities), or premature study treatment discontinuation due to an adverse event (regardless of grade).
Time frame: 72 weeks
Any serious adverse events
The number of participants with serious adverse events, regardless of relationship to 3BNC117-LS, 10-1074-LS and N-803.
Time frame: 72 weeks
Dosing completion
The proportion of participants who complete dosing with 3BNC117-LS, 10-1074-LS and N-803.
Time frame: 24 weeks
Viral rebound before or at week 24 post withdrawing ART
The number of participants experiencing viral rebound, defined as confirmed HIV-1 RNA \>200 copies/mL at or prior to week 24 of ART discontinuation.
Time frame: 24 weeks
ART not restarted by weeks 60 and 72
The proportion of participants who do not meet ART restart criteria by weeks 60 and 72.
Time frame: 72 weeks
ART not restarted when bNABs below threshold
The proportion of participants who do not meet ART restart criteria for 12 or more weeks after bNAbs are below a threshold of 10 mcg/ml.
Time frame: 72 weeks
Treatment-related Grade 2 adverse events
The number of participants with treatment-related solicited and unsolicited grade 2 adverse events.
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Time frame: 72 weeks
Viral rebound through Step 2
The number of participants experiencing viral rebound, defined as confirmed HIV-1 RNA \>200 copies/mL, through Step 2 of the study.
Time frame: 72 weeks
Time from ART withdrawal to re-initiating ART
Time from ART withdrawal to virologic or immunologic criteria (i.e. viral load, CD4 cell count, or development of severe acute retroviral syndrome) to reinitiate ART.
Time frame: 72 weeks
Viral rebound determined by Monogram assay
Time to viral rebound (confirmed HIV-1 RNA \>200 copies/mL) across different 3BNC117-LS and 10-1074-LS IC90s cut points determined by the Monogram PhenoSense assay.
Time frame: 72 weeks
Size of latent HIV-1 reservoir
Size of the latent HIV-1 reservoir, measured by IPDA and/or other appropriate assay, before, during (Step 1) and after dosing with 3BNC117-LS, 10-1074-LS and N-803 (Step 2), and after antibody concentrations have declined below a therapeutic threshold.
Time frame: 72 weeks
Changes in HIV-1 specific T Cell immune responses
Changes in HIV-1 specific T cell immune responses in peripheral blood, measured by ELISPOT, before, during (Step 1) and after dosing with 3BNC117-LS, 10-1074-LS and N-803 (Step 2), and after antibody concentrations have declined below a therapeutic threshold.
Time frame: 72 weeks
Half-life of 3BNC117-LS and 10-1074-LS
Half-life of 3BNC117-LS and 10-1074-LS, when administered in combination with N-803 to individuals with HIV during ART interruption.
Time frame: 72 weeks
Anti-drug antibodies (ADA)
The proportion of individuals with treatment-induced ADA against each bNAb or N-803 and magnitude of the response.
Time frame: 72 weeks