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

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

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

Study Overview

• Status: Recruiting
• Conditions: HIV/AIDS
• Intervention / Treatment: Drug: N-803

Detailed Description

This is a phase II, randomized, unblinded, controlled trial to investigate the safety, tolerability and immunomodulation effect of combining N-803 with antiretroviral therapy (ART) during acute HIV infection (AHI). The study will be conducted at one study site, the Thai Red Cross AIDS Research Centre (TRCARC) in Bangkok, Thailand.

Eligible participants will be asked to undergo LN Bx at baseline (untreated AHI), prior to initiating dolutegravir-based ART. N-803 will be administered subcutaneously at weeks 0, 3, 6 (total 3 doses) and will be initiated together with ART. Participants will be asked to undergo a second inguinal LN Bx on the opposite groin approximately at week 6 (no later than 1 week after completion of study agents). They will be followed for safety parameters at weeks 8 and 12, after which they will roll over to the RV412, WRAIR#2178 safety monitoring protocol. The study duration for individual participants will be approximately 12 weeks. The study may include additional optional procedures at baseline and week 6 such as leukapheresis, brain MRI imaging and lumbar puncture, according to participants' consent.

It is hypothesized that N-803 initiated with ART during AHI, will be safe, and will lead to a reduction of HIV reservoir size in LN, demonstrated by decreased frequencies of vRNA+ and vDNA+ cells in the LNs, in comparison with ART alone.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haoyu Qian; Phone Number: 301-500-3732; Email: HQian@hivresearch.org
• Study Contact Backup: Name: Nitiya Chomchey, PhD; Phone Number: 66828994433; Email: nitiya.c@searchthailand.org

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Thai Red Cross AIDS Research Centre
    • Contact: Kiat Ruxrungtham, MD; Phone Number: 66863353655; Email: kiat.r@chula.ac.th
    • Contact: Nitiya Chomchey, RN, PhD; Phone Number: 66828994433; Email: nitiya.c@searchthailand.org
    • Principal Investigator: Kiat Ruxrungtham, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-40 years
2. 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)
3. All female participants of childbearing potential must have a negative urine pregnancy test at the screening visit
4. 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
5. Can read and write Thai and/or English language and must be able to understand and complete the informed consent process
6. Must successfully complete a Test of Understanding (TOU) prior to enrollment as described in Section 7.1
7. Willing to undergo inguinal LN Bx at two time points (baseline and week 6) and blood draws during each study visit
8. Willing to participate for the duration of the study visits and follow up.

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
2. 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
3. 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.
4. Current or anticipated use of systemic steroid medications.
5. 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.)
6. Chronic liver disease
7. 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
8. History of potential immune-mediated medical conditions
9. Serious illness requiring systemic treatment and/or hospitalization in the 3 months prior to study enrollment
10. Major psychiatric illness and/or substance use during the past 12 months that in the opinion of the investigator would preclude participation
11. Concurrent treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 4 weeks prior to study enrollment
12. Exposure to any experimental therapies within 90 days of study entry
13. Pre-exposure prophylaxis (PrEP) use within 90 days of study entry

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-803; N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10)	Drug: N-803; N-803 is a novel IL-15 superagonist complex that enhances NK cell and CD8+ T-cell proliferation and activation.; Other Names: ALT-803
No Intervention: Control; ART alone (n=5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 in LNs (Efficacy)	Frequency of vRNA+ and vDNA+ cells in LNs	at week 6
levels of vDNA and vRNA in LNs (Efficacy)	levels of vDNA and vRNA in LNs	at week 6
Frequency of CD8+ T cells in LNs (Efficacy)	Frequency of CD8+ T cells in LNs	at week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Immune cells in LN and blood	Frequency of Immune cells in LN and blood	at week 6
HIV-specific antibody levels	HIV-specific antibody levels	at week 12
HIV-specific antibody function as measured by Antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and Antibody-dependent cell-mediated viral inhibition (ADCVI) levels.	HIV-specific antibody function as measured by Antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and Antibody-dependent cell-mediated viral inhibition (ADCVI) levels.	at week 12
Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)	Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)	at week 12
Differential expressed genes in LN and blood	Differential expressed genes in LN and blood	at week 12
Immune activation markers in blood	Immune activation markers in blood	at week 12
Immune activation markers in CSF	Immune activation markers in CSF	at week 6
Extent of cerebral inflammation in MR Spectroscopy (MRS)	Extent of cerebral inflammation in MR Spectroscopy (MRS)	at week 6
Viral load in the CSF	Viral load in the CSF	at week 6

Collaborators and Investigators

• Sponsor: Thai Red Cross AIDS Research Centre
• Collaborators: Walter Reed Army Institute of Research (WRAIR); Henry M. Jackson Foundation for the Advancement of Military Medicine
• Investigators: Study Chair: Sandhya C Vasan, MD PhD, Henry M. Jackson Foundation for the Advancement of Military Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections
• Other Study ID Numbers: RV550

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No