Effect of N-803 on B Cell Follicles in Antiretroviral Treated HIV Disease

NCT04808908 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IDIM-2019-273955UM1AI126611
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Hiv; HIV Infections; AIDS

Outcome Measures

Primary Outcomes (1)

• 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)

  6 months

Secondary Outcomes (1)

• Frequency of CD8+ T Cells in Follicles

  6 months

Study Arms (1)

N-803

EXPERIMENTAL

All participants will receive the intervention, N-803 treatment.

Biological: N-803

Interventions

N-803 BIOLOGICAL

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)

N-803

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, 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).
• 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:
• (1) 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)

You may not qualify if:

• 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
• coronary or other arterial revascularization
• stroke
• transient ischemic attack (TIA)
• peripheral arterial disease presumed to be of atherosclerotic origin.
• Unable to undergo leukapheresis procedure
• 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.

Sponsors & Collaborators

• University of Minnesota: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 40471871 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; 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; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Kevin Escandón
• Organization: University of Minnesota

escan012@umn.edu

612-626-9344

Study Officials

• Timothy Schacker, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 22, 2021
• Study Start: April 1, 2021
• Primary Completion: July 18, 2022
• Study Completion: January 1, 2023
• Last Updated: April 2, 2024
• Results First Posted: April 2, 2024

Record last verified: 2024-03

Locations

US (2)