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

NCT04340596 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ACTG A538638639
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 14

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).

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (4)

• Occurrence of a Grade ≥3 adverse event (AE) that is at least possibly related to N-803, as judged by the Clinical Management Committee (CMC)

  Step 2 week 1 to week 52

• Number of N-803 doses completed

  Eight doses of N-803 are scheduled at the distinct time points listed in Time Frame. At each timepoint, dose completion status is recorded. Number of N-803 doses completed is the total number completed doses across all 8 timepoints.

  From step 2 week 1 to step 2 week 22

• Proportion of participants requiring dose reduction

  Eight doses of N-803 are scheduled at distinct time points (Step 2 weeks 1, 4, 7, 10, 13, 16, 19 and 22). Proportion of participants requiring dose reduction is calculated as the number of participants who receive a reduced dose of N-803 at any of the 7 scheduled doses occurring after the first dose, divided by the total number of participants receiving N-803.

  From step 2 week 4 to step 2 week 22

• Proportion of participants with plasma HIV-1 RNA <200 copies/mL 8 weeks after interruption of ART

  At step 3 week 8

Secondary Outcomes (12)

• Occurrence of a Grade ≥2 AE without regard to relationship to study treatment

  Study entry to participant's last study visit, at approx. study week 100

• Occurrence of a Grade ≥2 AE that is at least possibly related to N-803, as judged by the CMC

  Step 2 week 1 to week 52

• Occurrence of a Grade ≥2 AE that is at least possibly related to VRC07-523LS or 10-1074

  Step 2 week 0 to week 52

• Cell-associated HIV-1 RNA

  At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32

• Measurement of HIV-1 reservoir (dQVOA)

  At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32

Study Arms (2)

Arm A: N-803 only

EXPERIMENTAL

Participants will receive N-803 6 mcg/kg 1 week after Step 2 entry and then every 3 weeks for a total of eight doses.

Biological: N-803 (IL-15 Superagonist)

Arm B: N-803 in combination with 10-1074 and VRC07-523LS

EXPERIMENTAL

Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows: * At Step 2 entry: * VRC07-523LS 20 mg/kg * 10-1074 30 mg/kg * At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses * At Step 2, week 9: 10-1074 30 mg/kg

Biological: N-803 (IL-15 Superagonist); Biological: VRC07-523LS; Biological: 10-1074

Interventions

N-803 (IL-15 Superagonist) BIOLOGICAL

Administered by subcutaneous (SQ) injection

Arm A: N-803 only; Arm B: N-803 in combination with 10-1074 and VRC07-523LS

VRC07-523LS BIOLOGICAL

Administered by intravenous (IV) infusion

Arm B: N-803 in combination with 10-1074 and VRC07-523LS

10-1074 BIOLOGICAL

Administered by intravenous (IV) infusion

Arm B: N-803 in combination with 10-1074 and VRC07-523LS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Rockefeller University: collaborator
• ImmunityBio, Inc.: collaborator

Study Sites (14)

Alabama CRS (Site ID# 31788)

Birmingham, Alabama, 35222, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

UCSD Antiviral Research Center CRS (Site ID: 701)

San Diego, California, 92103, United States

Location

University of California, San Fransisco HIV/AIDS CRS

San Francisco, California, 94110, United States

Location

Whitman-Walker Institute, Inc. CRS (Site ID: 31791)

Washington D.C., District of Columbia, 20005, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)

Boston, Massachusetts, 02114, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS [Site ID: 31786]

Newark, New Jersey, 07103, United States

Location

Columbia P&S CRS

New York, New York, 10032, United States

Location

Weill Cornell Uptown CRS (Site ID: 7803)

New York, New York, 10065, United States

Location

Chapel Hill CRS (Site ID: 3201)

Chapel Hill, North Carolina, 27599, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Therapeutics, CRS (Site ID: 6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

HIV Infections

Interventions

ALT-803

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Timothy Wilkin, MD, MPH

  Weill Medical College of Cornell University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: April 9, 2020
• Study Start: May 21, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (14)