Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection

NCT04505501 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RV550
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Reducing HIV persistence in lymph nodes by Interleukin-15 (IL-15) Receptor super-agonist (N-803) in Individuals with Acute HIV Infection

Conditions

HIV/AIDS

Outcome Measures

Primary Outcomes (4)

• Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety)

  Rate of occurrence of ≥ grade 3 adverse events determined to be related

  at time of study completion at week 12

• Frequency of vRNA+ and vDNA+ cells and levels of vDNA and vRNA in LNs

  Frequency of vRNA+ and vDNA+ cells and levels of vDNA and vRNA in LNs

  At baseline (week 0) and week 6

• Frequency, phenotype and function of CD8+ T cells and innate cells in LNs

  Frequency, phenotype and function of CD8+ T cells and innate cells in LNs

  At baseline (week 0) and week 6

• Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.

  Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.

  viral rebound during Step 2 ATI

Secondary Outcomes (9)

• Frequency, phenotype and function of NK, T, B and other immune cells in LNs and blood

  Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12

• HIV-specific antibody levels and ADCC, ADCP, ADCVI activities

  Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12

• Frequency of cells harboring HIV-1 vDNA, vRNA, intact genome and replication competent HIV-1 in PBMC

  Step 1 weeks 0, 3, 6, 12; Step 2 week 0; Step 3 week 12

• Host and viral genes by transcriptome analysis

  Step 1 week 0 and 6

• Immune activation markers in blood

  Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12

Study Arms (2)

N-803

EXPERIMENTAL

Step 1: N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10) Step 2 : N-803 at 6mcg/kg at week 0 single dose (n=8), ATI after N-803 injection until week 12 (If meet criteria to restart ART, participants will go to step 3). Step 3: ART restart (week 0 to week 12).

Drug: N-803

Control

NO INTERVENTION

Step 1: ART alone (n=5) Step 2 : N-803 at 6mcg/kg at week 0 single dose (n=8), ATI after N-803 injection until week 12 (If meet criteria to restart ART, participants will go to step 3). Step 3: ART restart (week 0 to week 12).

Interventions

N-803 DRUG

N-803 is a novel IL-15 superagonist complex that enhances NK cell and CD8+ T-cell proliferation and activation.

Also known as: ALT-803

N-803

Eligibility Criteria

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

You may qualify if:

• Age 18 years and above.
• Acute HIV infection (Fiebig I to V: Fiebig I: RNA+, p24 antigen-; Fiebig II: p24 antigen+, IgM-; Fiebig III: IgM+, Western Blot-; Fiebig IV: Western Blot indeterminate; Fiebig V: Western Blot+ without p31 protein band)
• All female participants of childbearing potential must have a negative urine pregnancy test at the screening visit
• Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception (as defined in section 8.1.2 Pregnancy Risks) during therapy and for 4 months after completion of therapy
• Can read and write Thai and/or English language and must be able to understand and complete the informed consent process
• Must successfully complete a Test of Understanding (TOU) prior to enrollment as described in Section 7.1
• Willing to undergo inguinal LN Bx at two time points (baseline and week 6) and blood draws during each study visit
• Willing to participate for the duration of the study visits and follow up.

You may not qualify if:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• Receipt of any vaccine within 2 weeks prior to study enrollment and anticipated need for any vaccine within 2 weeks prior to or after any of the study agent administrations.
• Current or anticipated use of systemic steroid medications.
• Any clinically significant acute or chronic medical condition, including, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, that in the opinion of the investigator would preclude participation (e.g., history of seizure disorders, cardiac disease, bleeding/clotting disorder, autoimmune disease, active malignancy, poorly controlled asthma, active tuberculosis or other systemic infections, etc.)
• Chronic liver disease
• Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the following: (a) acute myocardial infarction, (b) acute coronary syndromes, (c) stable or unstable angina, (d) coronary or other arterial revascularization, (e) stroke, (f) transient ischemic attack, or (g) peripheral arterial disease presumed to be of atherosclerotic origin
• History of potential immune-mediated medical conditions
• Serious illness requiring systemic treatment and/or hospitalization in the 3 months prior to study enrollment
• Major psychiatric illness and/or substance use during the past 12 months that in the opinion of the investigator would preclude participation
• Concurrent treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 4 weeks prior to study enrollment
• Exposure to any experimental therapies within 90 days of study entry
• Pre-exposure prophylaxis (PrEP) use within 90 days of study entry
• Completed Step 1 as per protocol
• Plasma HIV-1 RNA \<50 copies/mL at the Step 2 screening visit
• CD4 T-cell count ≥400 cells/mm3 at the Step 2 screening visit Note: The CD4 T-cell count can be repeated once, provided that the repeat is done within 1 week prior to Step 2 entry.

Sponsors & Collaborators

• Thai Red Cross AIDS Research Centre: lead
• Henry M. Jackson Foundation for the Advancement of Military Medicine: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Thai Red Cross AIDS Research Centre

Bangkok, Bangkok, 10330, Thailand

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

ALT-803

Condition Hierarchy (Ancestors)

HIV Infections; 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

Study Officials

• Sandhya C Vasan, MD PhD

  Henry M. Jackson Foundation for the Advancement of Military Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This study is unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: August 10, 2020
• Study Start: March 1, 2021
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: April 13, 2025

Record last verified: 2025-04

Locations

TH (1)