HivPhase 1NCT04808908
Effect of N-803 on B Cell Follicles in Antiretroviral Treated HIV Disease
A Phase 1 study testing N-803 in people with Hiv and HIV Infections, run by University of Minnesota at 2 sites in United States.
Trial summary
N-803 has demonstrated ability to reactivate HIV from latency and can activate T cells and NK cells to clear those cells, thus reducing the reservoir. However, a concern is that CD8 T cells may be excluded from the B cell follicles, where a significant part of the reservoir resides. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hiv, HIV Infections, AIDS
- What is being tested?
- N-803
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Apr 2021to 1 Jan 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load.
- On continuous antiretroviral therapy for over 24 months without any interruptions of greater than 14 consecutive days, without plans to modify ARTduring the study period.
- Screening plasma HIV RNA levels < 20 copies/mL and on at least 1 determination in past 12 months (isolated single values greater than or equal to 20 but < 200 copies/mL will be allowed if they were preceded and followed by undetectable viral load determinations)
- Screening CD4+ T cell count greater than or equal to 350 cells/mm3 and nadir CD4+ T cell count of >200 per participant report.
- Ability to be off prednisone and other immunosuppressive drugs for at least 14 days before screen. Inhaled, nasal spray, and topical steroids are acceptable.
- Acceptable blood pressure and heart rate parameters within normal limits (systolic = 88-140mmHg; diastolic = 50-<90mmHg; heart rate = 46-100 bpm). Treatment with antihypertensive medication is allowed. However, if someone is on a beta-blocker this must be switched to another class of medication as there is a theoretical risk for bradycardia if the participant were to experience cytokine release syndrome symptoms (which has not happened with this drug delivered SQ).
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- Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during study participation and for 1 month following the final study visit (4 months after final dose of study drug). Acceptable birth control is defined as the following:
- For female participants of childbearing potential, two of the following forms of contraception are required, one of which must be a barrier method:
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD) with published data showing that expected failure rate is < 1% per year
- Tubal ligation
- Hormone-based contraceptive such as oral birth control pills
- Laboratory tests performed within 14 days of study enrollment must be a grade 0 or 1 as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, with the following exceptions:
- Platelet counts (≥ 150,000/mm3)
- Hemoglobin > 12.5 g/dL for men and > 11.5 g/dL for women. It is not acceptable for patients to be transfused to meet this requirement. The use of Epogen is permitted.
- Estimated Cr Cl (eGFR) > 50
Who cannot join
- Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months; minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) are not exclusionary
- Chronic liver disease defined as Class B and C on the Child-Pugh chronic liver disease scale.
- Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the following:
- acute myocardial infarction
- acute coronary syndromes
- stable or unstable angina
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- coronary or other arterial revascularization
- stroke
- transient ischemic attack (TIA)
- peripheral arterial disease presumed to be of atherosclerotic origin.
- History of potential immune-mediated medical conditions requiring concomitant treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 30 days prior to screen (e.g. corticosteroid therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days, IL-2, interferon, methotrexate, cancer chemotherapy). NOTE: use of inhaled, nasal steroid or topical steroid lotions and creams is not exclusionary. Prior exposure to N-803 is not exclusionary if prior exposure occurred at least 6 months before screen.
- Unable to undergo leukapheresis procedure
- Exposure to any experimental therapies within 90 days of study screen. Exposure to long acting injectable ART therapies is not exclusionary.
- Latent TB infection or active TB disease prior to completing a standard regimen of anti-TB therapy that is defined as meeting PPD criteria for TB exposure or a positive quantiferon gold test collected at screening.
- Active fungal infection requiring systemic antifungal therapy
- Active herpes outbreak or varicella-zoster virus infection requiring episodic treatment
- Chronic active hepatitis B or C. For Hepatitis B this will be defined as HBs antigen + and for Hepatitis C this will be defined as Hepatitis C antibody positive and Hepatitis C PCR+.
- History and/or presence of any clinically significant disease or disorder, such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and psychiatric/mental disease/disorder, which, in the opinion of the site Principle Investigator may either put the subject at risk because of participation in the study, influence the results of the study or the subject's ability to participate in the study.
- Any degree of baseline QT/QTc interval prolongation (QTc interval > 450 msec in males and > 470 msec in females.)
- Any ischemic changes seen in the stress treadmill test administered per the discretion of the PI in order to assess any other EKG abnormalities outlined in study protocol
- History or evidence of uncontrollable CNS disease such as dementia, demyelinating disease, Parkinson's, or a CNS degenerative disease that, in the opinion of the site Principle Investigator, may either put the subject at risk because of participation in the study, influence the results of the study or the subject's ability to participate in the study.
- Prior organ allograft or allogeneic transplantation
- Planning or current pregnancy or breastfeeding
- Any clinically indicated vaccination (other than influenza) administered within 14 days of screen
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
N-803 has demonstrated ability to reactivate HIV from latency and can activate T cells and NK cells to clear those cells, thus reducing the reservoir. However, a concern is that CD8 T cells may be excluded from the B cell follicles, where a significant part of the reservoir resides. Webb, et al, has shown that in SIV infected monkeys CD8 T cells in follicles increase in frequency when N-803 is administered. We hypothesize that in HIV infected humans treated with N-803 that CD8 T cells will increase in B cell follicles and that there will be a further reduction in the frequency of cells with an inducible provirus.
Read the detailed description
A phase 1B single arm study of 10 HIV-infected adults on effective ART will be performed. This is a two-center, non-randomized, open label, and uncontrolled study.
All participants will undergo an extensive baseline evaluation 7-14 days before the first dose that will include an excisional biopsy of a lymph node, colonic biopsies, and leukapheresis. Participants will then receive three doses of N-803 administered every 21 days. A second excisional biopsy will be performed between 7-14 days after the final dose. The study drug N-803 will be administered at 6 mcg/kg, which is the maximum tolerated dose determined in a recently completed dose-escalation study.
- Conditions
- Hiv, HIV Infections, AIDS
- Being tested
- N-803
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-803Biological
N-803, provided by ImmunityBio., Inc. will be administered subcutaneously at a dose 6 mcg/kg on Days 0, 21, and 42 (with a dosing window of up to 14 days post the planned dosing day)
| Study group | Role | What they receive |
|---|---|---|
| N-803 | Experimental | All participants will receive the intervention, N-803 treatment. Receives: Biological: N-803 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Adverse Event Rate)
Safety is a primary outcome of this phase 1b trial. Safety will be reported as the number of adverse events per participant.
This includes all adverse events (total regardless of severity)
Measured: 6 months
Secondary outcomes (1)
Frequency of CD8+ T Cells in Follicles
Frequency of CD8+ T cells in B cell follicles will be determined using flow cytometry and reported in units of cells/g tissue
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2021
- Study start1 Apr 2021
- Primary completion18 Jul 2022
- Study completion1 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HivStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy Schacker, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04808908
- Sponsor's protocol ID
- IDIM-2019-27395
- Other IDs
- 5UM1AI126611
- Status last verified
- Mar 2024
- First submitted
- 18 Mar 2021
- Last updated
- 2 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rhein J, Chipman JG, Beilman GJ, Cromarty R, Escandon K, Anderson J, Wieking G, Reichel J, Batres R, Khoruts A, Basting CM, Hinderlie P, Davis ZB, Eaton A, Vaughn BP, Eilkhani E, Safrit JT, Soon-Shiong P, Baker JV, Klatt NR, Deeks SG, Miller JS, Schacker TW. Impact of the IL-15 superagonist N-803 on lymphatic reservoirs of HIV. JCI Insight. 2025 Jun 3;10(13):e190831. doi: 10.1172/jci.insight.190831. eCollection 2025 Jul 8.
PubMed 40471871
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of N-803 on B Cell Follicles in Antiretroviral Treated HIV Disease
- ClinicalTrials.gov ID
- NCT04808908
- Acronym / sponsor ID
- IDIM-2019-27395
- Conditions
- Hiv, HIV Infections, AIDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 18 Jul 2022 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 22 Mar 2021 (actual)
- Results
- Posted 2 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
N-803 has demonstrated ability to reactivate HIV from latency and can activate T cells and NK cells to clear those cells, thus reducing the reservoir. However, a concern is that CD8 T cells may be excluded from the B cell follicles, where a significant part of the reservoir resides. Webb, et al, has shown that in SIV infected monkeys CD8 T cells in follicles increase in frequency when N-803 is administered. We hypothesize that in HIV infected humans treated with N-803 that CD8 T cells will increase in B cell follicles and that there will be a further reduction in the frequency of cells with an inducible provirus.
Detailed description
A phase 1B single arm study of 10 HIV-infected adults on effective ART will be performed. This is a two-center, non-randomized, open label, and uncontrolled study.
All participants will undergo an extensive baseline evaluation 7-14 days before the first dose that will include an excisional biopsy of a lymph node, colonic biopsies, and leukapheresis. Participants will then receive three doses of N-803 administered every 21 days. A second excisional biopsy will be performed between 7-14 days after the final dose. The study drug N-803 will be administered at 6 mcg/kg, which is the maximum tolerated dose determined in a recently completed dose-escalation study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N-803 | Experimental | Biological: N-803All participants will receive the intervention, N-803 treatment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load.
- On continuous antiretroviral therapy for over 24 months without any interruptions of greater than 14 consecutive days, without plans to modify ARTduring the study period.
- Screening plasma HIV RNA levels < 20 copies/mL and on at least 1 determination in past 12 months (isolated single values greater than or equal to 20 but < 200 copies/mL will be allowed if they were preceded and followed by undetectable viral load determinations)
- Screening CD4+ T cell count greater than or equal to 350 cells/mm3 and nadir CD4+ T cell count of >200 per participant report.
- Ability to be off prednisone and other immunosuppressive drugs for at least 14 days before screen. Inhaled, nasal spray, and topical steroids are acceptable.
Key exclusion criteria (24 listed)
- Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months; minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) are not exclusionary
- Chronic liver disease defined as Class B and C on the Child-Pugh chronic liver disease scale.
- Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the following:
- History of potential immune-mediated medical conditions requiring concomitant treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 30 days prior to screen (e.g. corticosteroid therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days, IL-2, interferon, methotrexate, cancer chemotherapy). NOTE: use of inhaled, nasal steroid or topical steroid lotions and creams is not exclusionary. Prior exposure to N-803 is not exclusionary if prior exposure occurred at least 6 months before screen.
- Unable to undergo leukapheresis procedure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-803N-803, provided by ImmunityBio., Inc. will be administered subcutaneously at a dose 6 mcg/kg on Days 0, 21, and 42 (with a dosing window of up to 14 days post the planned dosing day) | Biological | N-803 |
Primary outcome
Safety (Adverse Event Rate)
Time frame: 6 months
Safety is a primary outcome of this phase 1b trial. Safety will be reported as the number of adverse events per participant. This includes all adverse events (total regardless of severity)
1 secondary outcome
Frequency of CD8+ T Cells in Follicles
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40471871Rhein J, Chipman JG, Beilman GJ, Cromarty R, Escandon K, Anderson J, Wieking G, Reichel J, Batres R, Khoruts A, Basting CM, Hinderlie P, Davis ZB, Eaton A, Vaughn BP, Eilkhani E, Safrit JT, Soon-Shiong P, Baker JV, Klatt NR, Deeks SG, Miller JS, Schacker TW. Impact of the IL-15 superagonist N-803 on lymphatic reservoirs of HIV. JCI Insight. 2025 Jun 3;10(13):e190831. doi: 10.1172/jci.insight.190831. eCollection 2025 Jul 8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy Schacker, MD principal investigator
University of Minnesota
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-803 in people with Hiv and HIV Infections, run by University of Minnesota at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Adverse Event Rate) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04808908, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.