Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection
Primary Purpose
HIV/AIDS
Status
Recruiting
Phase
Phase 2
Locations
Thailand
Study Type
Interventional
Intervention
N-803
Sponsored by
About this trial
This is an interventional treatment trial for HIV/AIDS
Eligibility Criteria
Inclusion Criteria:
- Age 18-40 years
- 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.
Exclusion Criteria:
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
- 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
- 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
Sites / Locations
- Thai Red Cross AIDS Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
N-803
Control
Arm Description
N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10)
ART alone (n=5)
Outcomes
Primary Outcome Measures
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
Frequency of vRNA+ and vDNA+ cells in LNs (Efficacy)
Frequency of vRNA+ and vDNA+ cells in LNs
levels of vDNA and vRNA in LNs (Efficacy)
levels of vDNA and vRNA in LNs
Frequency of CD8+ T cells in LNs (Efficacy)
Frequency of CD8+ T cells in LNs
Secondary Outcome Measures
Frequency of Immune cells in LN and blood
Frequency of Immune cells in LN and blood
HIV-specific antibody levels
HIV-specific antibody 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.
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.
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)
Differential expressed genes in LN and blood
Differential expressed genes in LN and blood
Immune activation markers in blood
Immune activation markers in blood
Immune activation markers in CSF
Immune activation markers in CSF
Extent of cerebral inflammation in MR Spectroscopy (MRS)
Extent of cerebral inflammation in MR Spectroscopy (MRS)
Viral load in the CSF
Viral load in the CSF
Full Information
NCT ID
NCT04505501
First Posted
July 13, 2020
Last Updated
June 14, 2023
Sponsor
Thai Red Cross AIDS Research Centre
Collaborators
Henry M. Jackson Foundation for the Advancement of Military Medicine, Walter Reed Army Institute of Research (WRAIR)
1. Study Identification
Unique Protocol Identification Number
NCT04505501
Brief Title
Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection
Official Title
Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Individuals With Acute HIV Infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thai Red Cross AIDS Research Centre
Collaborators
Henry M. Jackson Foundation for the Advancement of Military Medicine, Walter Reed Army Institute of Research (WRAIR)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Reducing HIV persistence in lymph nodes by Interleukin-15 (IL-15) Receptor super-agonist (N-803) in Individuals with Acute HIV Infection
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV/AIDS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
This study is unblinded.
Allocation
Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
N-803
Arm Type
Experimental
Arm Description
N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10)
Arm Title
Control
Arm Type
No Intervention
Arm Description
ART alone (n=5)
Intervention Type
Drug
Intervention Name(s)
N-803
Other Intervention Name(s)
ALT-803
Intervention Description
N-803 is a novel IL-15 superagonist complex that enhances NK cell and CD8+ T-cell proliferation and activation.
Primary Outcome Measure Information:
Title
Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety)
Description
Rate of occurrence of ≥ grade 3 adverse events determined to be related
Time Frame
at time of study completion at week 12
Title
Frequency of vRNA+ and vDNA+ cells in LNs (Efficacy)
Description
Frequency of vRNA+ and vDNA+ cells in LNs
Time Frame
at week 6
Title
levels of vDNA and vRNA in LNs (Efficacy)
Description
levels of vDNA and vRNA in LNs
Time Frame
at week 6
Title
Frequency of CD8+ T cells in LNs (Efficacy)
Description
Frequency of CD8+ T cells in LNs
Time Frame
at week 6
Secondary Outcome Measure Information:
Title
Frequency of Immune cells in LN and blood
Description
Frequency of Immune cells in LN and blood
Time Frame
at week 6
Title
HIV-specific antibody levels
Description
HIV-specific antibody levels
Time Frame
at week 12
Title
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.
Description
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.
Time Frame
at week 12
Title
Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)
Description
Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)
Time Frame
at week 12
Title
Differential expressed genes in LN and blood
Description
Differential expressed genes in LN and blood
Time Frame
at week 12
Title
Immune activation markers in blood
Description
Immune activation markers in blood
Time Frame
at week 12
Title
Immune activation markers in CSF
Description
Immune activation markers in CSF
Time Frame
at week 6
Title
Extent of cerebral inflammation in MR Spectroscopy (MRS)
Description
Extent of cerebral inflammation in MR Spectroscopy (MRS)
Time Frame
at week 6
Title
Viral load in the CSF
Description
Viral load in the CSF
Time Frame
at week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-40 years
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.
Exclusion Criteria:
Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nitiya Chomchey, PhD
Phone
66828994433
Email
nitiya.c@searchthailand.org
First Name & Middle Initial & Last Name or Official Title & Degree
Haoyu Qian
Phone
301-500-3732
Email
HQian@hivresearch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandhya C Vasan, MD PhD
Organizational Affiliation
Henry M. Jackson Foundation for the Advancement of Military Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Thai Red Cross AIDS Research Centre
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitiya Chomchey, RN, PhD
Phone
66828994433
Email
nitiya.c@searchthailand.org
First Name & Middle Initial & Last Name & Degree
Kiat Ruxrungtham, MD
Phone
66863353655
Email
kiat.r@chula.ac.th
First Name & Middle Initial & Last Name & Degree
Kiat Ruxrungtham, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection
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