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

March 24, 2025 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will 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).

Participants will be screened for eligibility and undergo leukapheresis, and a subset will also undergo optional rectal biopsy and/or lymph node fine needle aspirations (FNAs) (Step 1).

After pre-entry and determination of eligibility in Step 1, participants will be randomized before Step 2 entry to either the N-803 only arm (Arm A) or the N-803 with combination bNAbs arm (Arm B):

  • Arm A will receive a dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses (during the first 22 weeks).

  • Arm B will receive the following (during the first 22 weeks):

    • Combination bNAb at Step 2 entry with VRC07-523LS dosed at 20 mg/kg and 10-1074 dosed at 30 mg/kg, intravenously;
    • A dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses;
    • A second dose of 10-1074 at week 9 of Step 2 dosed at 30 mg/kg, intravenously

After completing randomized treatment (Step 2), participants will interrupt antiretroviral therapy (ART) (Step 3) and will be followed closely to monitor for indications for reinitiation of ART (Step 4).

After Step 2 entry, most participants will be followed for approximately 100 weeks across the remaining three study steps (i.e., Steps 2, 3, and 4).

Step 1 will last up to 90 days, Step 2 will last approximately 52 weeks (study intervention), Step 3 will last up to 24 weeks (ATI), and Step 4 will last 24 weeks (ART restart).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
118

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35222
        • Alabama CRS (Site ID# 31788)
    • California
      • Los Angeles, California, United States, 90035
        • UCLA CARE Center CRS
      • San Diego, California, United States, 92103
        • UCSD Antiviral Research Center CRS (Site ID: 701)
      • San Francisco, California, United States, 94110
        • University of California, San Fransisco HIV/AIDS CRS
    • District of Columbia
      • Washington, District of Columbia, United States, 20005
        • Whitman-Walker Institute, Inc. CRS (Site ID: 31791)
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)
    • Missouri
      • Saint Louis, Missouri, United States, 63110-1010
        • Washington University Therapeutics (WT) CRS
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • New Jersey Medical School Clinical Research Center CRS [Site ID: 31786]
    • New York
      • New York, New York, United States, 10032
        • Columbia P&S CRS
      • New York, New York, United States, 10065
        • Weill Cornell Uptown CRS (Site ID: 7803)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Chapel Hill CRS (Site ID: 3201)
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Clinical Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Penn Therapeutics, CRS (Site ID: 6201)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A: N-803 only
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)
Administered by subcutaneous (SQ) injection
Experimental: Arm B: N-803 in combination with 10-1074 and VRC07-523LS

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: VRC07-523LS
Administered by intravenous (IV) infusion
Biological: N-803 (IL-15 Superagonist)
Administered by subcutaneous (SQ) injection
Biological: 10-1074
Administered by intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Step 2 week 1 to week 52
Step 2 week 1 to week 52
Number of N-803 doses completed
Time Frame: From step 2 week 1 to step 2 week 22
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
Time Frame: From step 2 week 4 to step 2 week 22
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
Time Frame: At step 3 week 8
At step 3 week 8

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Occurrence of a Grade ≥2 AE without regard to relationship to study treatment
Time Frame: Study entry to participant's last study visit, at approx. study week 100
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
Time Frame: Step 2 week 1 to week 52
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
Time Frame: Step 2 week 0 to week 52
Step 2 week 0 to week 52
Cell-associated HIV-1 RNA
Time Frame: At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Measurement of HIV-1 reservoir (dQVOA)
Time Frame: At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Measurement of plasma viremia by HIV-1 single copy assay
Time Frame: At step 1 pre-entry evaluation and step 2 weeks 0, 1, 7, 13, 22 and 32
At step 1 pre-entry evaluation and step 2 weeks 0, 1, 7, 13, 22 and 32
Measurement of intact proviral DNA
Time Frame: At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Total HIV-1 DNA
Time Frame: At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Proportion of participants with plasma HIV-1 RNA <200 copies/mL at 4, 12 and 24 weeks after interruption of ART in Step 3
Time Frame: At step 3 weeks 4, 12, and 24
At step 3 weeks 4, 12, and 24
PK parameters: AUC0-τ of 10-1074
Time Frame: At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
PK parameters: AUC0-τ of VRC07-523LS
Time Frame: At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
Proportion of participants with antidrug antibodies
Time Frame: At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
Presence of anti-N803, anti-10-1074, and anti-VRC07-523LS antibodies
At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ImmunityBio, Inc.
Rockefeller University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Timothy Wilkin, MD, MPH, Weill Medical College of Cornell University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 21, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 23, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 9, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACTG A5386
  • 38639 (Registry Identifier: DAIDS-ES Registry Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie results in the publication, after deidentification.

IPD Sharing Time Frame

Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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