<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04505501</url>
  </required_header>
  <id_info>
    <org_study_id>RV550</org_study_id>
    <nct_id>NCT04505501</nct_id>
  </id_info>
  <brief_title>Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection</brief_title>
  <official_title>Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Individuals With Acute HIV Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thai Red Cross AIDS Research Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Henry M. Jackson Foundation for the Advancement of Military Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Walter Reed Army Institute of Research (WRAIR)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Thai Red Cross AIDS Research Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Reducing HIV persistence in lymph nodes by Interleukin-15 (IL-15) Receptor super-agonist&#xD;
      (N-803) in Individuals with Acute HIV Infection&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II, randomized, unblinded, controlled trial to investigate the safety,&#xD;
      tolerability and immunomodulation effect of combining N-803 with antiretroviral therapy (ART)&#xD;
      during acute HIV infection (AHI). The study will be conducted at one study site, the Thai Red&#xD;
      Cross AIDS Research Centre (TRCARC) in Bangkok, Thailand.&#xD;
&#xD;
      Eligible participants will be asked to undergo LN Bx at baseline (untreated AHI), prior to&#xD;
      initiating dolutegravir-based ART. N-803 will be administered subcutaneously at weeks 0, 3, 6&#xD;
      (total 3 doses) and will be initiated together with ART. Participants will be asked to&#xD;
      undergo a second inguinal LN Bx on the opposite groin approximately at week 6 (no later than&#xD;
      1 week after completion of study agents). They will be followed for safety parameters at&#xD;
      weeks 8 and 12, after which they will roll over to the RV412, WRAIR#2178 safety monitoring&#xD;
      protocol. The study duration for individual participants will be approximately 12 weeks. The&#xD;
      study may include additional optional procedures at baseline and week 6 such as&#xD;
      leukapheresis, brain MRI imaging and lumbar puncture, according to participants' consent.&#xD;
&#xD;
      It is hypothesized that N-803 initiated with ART during AHI, will be safe, and will lead to a&#xD;
      reduction of HIV reservoir size in LN, demonstrated by decreased frequencies of vRNA+ and&#xD;
      vDNA+ cells in the LNs, in comparison with ART alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This study is unblinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety)</measure>
    <time_frame>at time of study completion at week 12</time_frame>
    <description>Rate of occurrence of ≥ grade 3 adverse events determined to be related</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of vRNA+ and vDNA+ cells in LNs (Efficacy)</measure>
    <time_frame>at week 6</time_frame>
    <description>Frequency of vRNA+ and vDNA+ cells in LNs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>levels of vDNA and vRNA in LNs (Efficacy)</measure>
    <time_frame>at week 6</time_frame>
    <description>levels of vDNA and vRNA in LNs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of CD8+ T cells in LNs (Efficacy)</measure>
    <time_frame>at week 6</time_frame>
    <description>Frequency of CD8+ T cells in LNs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of Immune cells in LN and blood</measure>
    <time_frame>at week 6</time_frame>
    <description>Frequency of Immune cells in LN and blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV-specific antibody levels</measure>
    <time_frame>at week 12</time_frame>
    <description>HIV-specific antibody levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>at week 12</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)</measure>
    <time_frame>at week 12</time_frame>
    <description>Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differential expressed genes in LN and blood</measure>
    <time_frame>at week 12</time_frame>
    <description>Differential expressed genes in LN and blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune activation markers in blood</measure>
    <time_frame>at week 12</time_frame>
    <description>Immune activation markers in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune activation markers in CSF</measure>
    <time_frame>at week 6</time_frame>
    <description>Immune activation markers in CSF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent of cerebral inflammation in MR Spectroscopy (MRS)</measure>
    <time_frame>at week 6</time_frame>
    <description>Extent of cerebral inflammation in MR Spectroscopy (MRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral load in the CSF</measure>
    <time_frame>at week 6</time_frame>
    <description>Viral load in the CSF</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>HIV/AIDS</condition>
  <arm_group>
    <arm_group_label>N-803</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>ART alone (n=5)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-803</intervention_name>
    <description>N-803 is a novel IL-15 superagonist complex that enhances NK cell and CD8+ T-cell proliferation and activation.</description>
    <arm_group_label>N-803</arm_group_label>
    <other_name>ALT-803</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-40 years&#xD;
&#xD;
          2. Acute HIV infection (Fiebig I to V: Fiebig I: RNA+, p24 antigen-; Fiebig II: p24&#xD;
             antigen+, IgM-; Fiebig III: IgM+, Western Blot-; Fiebig IV: Western Blot&#xD;
             indeterminate; Fiebig V: Western Blot+ without p31 protein band)&#xD;
&#xD;
          3. All female participants of childbearing potential must have a negative urine pregnancy&#xD;
             test at the screening visit&#xD;
&#xD;
          4. Women of child bearing potential and men with partners of child bearing potential must&#xD;
             agree to use effective contraception (as defined in section 8.1.2 Pregnancy Risks)&#xD;
             during therapy and for 4 months after completion of therapy&#xD;
&#xD;
          5. Can read and write Thai and/or English language and must be able to understand and&#xD;
             complete the informed consent process&#xD;
&#xD;
          6. Must successfully complete a Test of Understanding (TOU) prior to enrollment as&#xD;
             described in Section 7.1&#xD;
&#xD;
          7. Willing to undergo inguinal LN Bx at two time points (baseline and week 6) and blood&#xD;
             draws during each study visit&#xD;
&#xD;
          8. Willing to participate for the duration of the study visits and follow up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant, breastfeeding, or unwilling to practice birth control during participation&#xD;
             in the study&#xD;
&#xD;
          2. Active or recent malignancy requiring systemic chemotherapy or surgery in the&#xD;
             preceding 36 months or for whom such therapies are expected in the subsequent 12&#xD;
             months; minor surgical removal of localized skin cancers (squamous cell carcinoma,&#xD;
             basal cell carcinoma) are not exclusionary&#xD;
&#xD;
          3. Receipt of any vaccine within 2 weeks prior to study enrollment and anticipated need&#xD;
             for any vaccine within 2 weeks prior to or after any of the study agent&#xD;
             administrations.&#xD;
&#xD;
          4. Current or anticipated use of systemic steroid medications.&#xD;
&#xD;
          5. Any clinically significant acute or chronic medical condition, including, pulmonary,&#xD;
             hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, that in&#xD;
             the opinion of the investigator would preclude participation (e.g., history of seizure&#xD;
             disorders, cardiac disease, bleeding/clotting disorder, autoimmune disease, active&#xD;
             malignancy, poorly controlled asthma, active tuberculosis or other systemic&#xD;
             infections, etc.)&#xD;
&#xD;
          6. Chronic liver disease&#xD;
&#xD;
          7. Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as&#xD;
             defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the&#xD;
             following: (a) acute myocardial infarction, (b) acute coronary syndromes, (c) stable&#xD;
             or unstable angina, (d) coronary or other arterial revascularization, (e) stroke, (f)&#xD;
             transient ischemic attack, or (g) peripheral arterial disease presumed to be of&#xD;
             atherosclerotic origin&#xD;
&#xD;
          8. History of potential immune-mediated medical conditions&#xD;
&#xD;
          9. Serious illness requiring systemic treatment and/or hospitalization in the 3 months&#xD;
             prior to study enrollment&#xD;
&#xD;
         10. Major psychiatric illness and/or substance use during the past 12 months that in the&#xD;
             opinion of the investigator would preclude participation&#xD;
&#xD;
         11. Concurrent treatment with immunomodulatory drugs, and/or exposure to any&#xD;
             immunomodulatory drug in the 4 weeks prior to study enrollment&#xD;
&#xD;
         12. Exposure to any experimental therapies within 90 days of study entry&#xD;
&#xD;
         13. Pre-exposure prophylaxis (PrEP) use within 90 days of study entry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandhya C Vasan, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Henry M. Jackson Foundation for the Advancement of Military Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nitiya Chomchey, PhD</last_name>
    <phone>66828994433</phone>
    <email>nitiya.c@searchthailand.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Haoyu Qian</last_name>
    <phone>301-500-3732</phone>
    <email>HQian@hivresearch.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Thai Red Cross AIDS Research Centre</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nitiya Chomchey, RN, PhD</last_name>
      <phone>66828994433</phone>
      <email>nitiya.c@searchthailand.org</email>
    </contact>
    <contact_backup>
      <last_name>Kiat Ruxrungtham, MD</last_name>
      <phone>66863353655</phone>
      <email>kiat.r@chula.ac.th</email>
    </contact_backup>
    <investigator>
      <last_name>Kiat Ruxrungtham, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>June 14, 2023</last_update_submitted>
  <last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04505501
org study id: RV550
nct id: NCT04505501
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Reducing HIV persistence in lymph nodes by Interleukin-15 (IL-15) Receptor super-agonist
      (N-803) in Individuals with Acute HIV Infection
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: This study is unblinded.
measure: Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety)
time frame: at time of study completion at week 12
description: Rate of occurrence of ≥ grade 3 adverse events determined to be related
measure: Frequency of vRNA+ and vDNA+ cells in LNs (Efficacy)
time frame: at week 6
description: Frequency of vRNA+ and vDNA+ cells in LNs
measure: levels of vDNA and vRNA in LNs (Efficacy)
time frame: at week 6
description: levels of vDNA and vRNA in LNs
measure: Frequency of CD8+ T cells in LNs (Efficacy)
time frame: at week 6
description: Frequency of CD8+ T cells in LNs
measure: Frequency of Immune cells in LN and blood
time frame: at week 6
description: Frequency of Immune cells in LN and blood
measure: HIV-specific antibody levels
time frame: at week 12
description: HIV-specific antibody levels
measure: 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
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.
measure: Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)
time frame: at week 12
description: Frequency of cells harboring vDNA, vRNA, intact genome and replication competent HIV-1 in peripheral blood mononuclear cell (PBMC)
measure: Differential expressed genes in LN and blood
time frame: at week 12
description: Differential expressed genes in LN and blood
measure: Immune activation markers in blood
time frame: at week 12
description: Immune activation markers in blood
measure: Immune activation markers in CSF
time frame: at week 6
description: Immune activation markers in CSF
measure: Extent of cerebral inflammation in MR Spectroscopy (MRS)
time frame: at week 6
description: Extent of cerebral inflammation in MR Spectroscopy (MRS)
measure: Viral load in the CSF
time frame: at week 6
description: Viral load in the CSF
arm group label: N-803
arm group type: Experimental
description: N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10)
arm group label: Control
arm group type: No Intervention
description: ART alone (n=5)
intervention type: Drug
intervention name: N-803
description: N-803 is a novel IL-15 superagonist complex that enhances NK cell and CD8+ T-cell proliferation and activation.
arm group label: N-803
other name: ALT-803
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Sandhya C Vasan, MD PhD
role: Study Chair
affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine
last name: Nitiya Chomchey, PhD
phone: 66828994433
email: nitiya.c@searchthailand.org
last name: Haoyu Qian
phone: 301-500-3732
email: HQian@hivresearch.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Thailand
responsible party type: Sponsor
mesh term: HIV Infections