<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/NCT02191098</url>
  </required_header>
  <id_info>
    <org_study_id>1508M77601-1</org_study_id>
    <nct_id>NCT02191098</nct_id>
  </id_info>
  <brief_title>Proof of Principle Study of Pulse Dosing of IL-15 to Deplete the Reservoir in HIV Infected People</brief_title>
  <acronym>ALT-803</acronym>
  <official_title>Proof of Principle Study of Pulse Dosing of IL-15 to Deplete the Reservoir in HIV Infected People on Optimized ART With Undetectable Plasma HIV RNA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the safety and tolerability of ALT-803, as well as, the potential efficacy of&#xD;
      ALT-803 in HIV&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single-arm intra-patient dose escalating pilot study of ALT-803, a&#xD;
      recombinant human super agonist interleukin-15 (IL-15) complex with an expansion cohort at&#xD;
      the maximum tolerated dose (MTD). The primary aim is to investigate the safety and&#xD;
      tolerability of ALT-803 in HIV-infected people receiving potent and optimized antiretroviral&#xD;
      therapy. All infusions will occur on a Monday. Subjects will be monitored for 24 hours after&#xD;
      the first infusion and then for 6 hours after each subsequent infusion, provided no&#xD;
      unacceptable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2015</start_date>
  <completion_date type="Actual">September 9, 2019</completion_date>
  <primary_completion_date type="Actual">September 9, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the safety and tolerability of ALT-803 in HIV-infected subjects</measure>
    <time_frame>4 weeks</time_frame>
    <description>Safety and tolerability is determined by the incidence of adverse events, size of the inducible reservoir as estimated using the TILDA assay</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the impact of ALT-803 on the size of the inducible reservoir,</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assess the impact of ALT-803 on the size of the inducible reservoir, as estimated using the TILDA assay, in total CD4+ T cells and memory subsets</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>HIV</condition>
  <condition>Stable ART</condition>
  <arm_group>
    <arm_group_label>ALT-803</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ALT-803</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALT-803</intervention_name>
    <description>Interleukin 15 (IL-15) is a common γ-chain cytokine that is related to interleukin-2 (IL-2) and is a critical factor for the development, proliferation, and activation of effector natural killer (NK) and CD8+ memory T cells</description>
    <arm_group_label>ALT-803</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HIV-1 infected adults aged 18 years or over.&#xD;
&#xD;
          2. Stable ART for at least 36 months&#xD;
&#xD;
          3. Screening plasma HIV RNA levels below level of quantification (&lt;40 to &lt;50 copies&#xD;
             RNA/mL depending on the assay) ≥ 2 years (a single measurement above the level of&#xD;
             detection but &lt; 100-200 copies/ml will be allowed)&#xD;
&#xD;
          4. Screening CD4 count ≥500 cells/mm3&#xD;
&#xD;
          5. Laboratory tests performed within 14 days of study enrollment:&#xD;
&#xD;
               1. WBC ≥ 3000/mm3&#xD;
&#xD;
               2. Platelets ≥ 50,000/mm3 [Patients may be transfused to meet this requirement]&#xD;
&#xD;
               3. Hemoglobin ≥ 8 g/dL (&gt;80g/L) [Patients may be transfused to meet this&#xD;
                  requirement]&#xD;
&#xD;
               4. Calculated glomerular filtration rate (GFR) &gt;45 mL/min/1.73m2&#xD;
&#xD;
               5. Total bilirubin ≤ 2.0 X upper limit of institutional normal (ULN)&#xD;
&#xD;
               6. AST, ALT, ALP ≤ 2.0 X ULN&#xD;
&#xD;
          6. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction.&#xD;
             PFTs &gt; 50% of predicted if symptomatic or prior known impairment.&#xD;
&#xD;
          7. Ability to be off prednisone and other immunosuppressive drugs for at least 14 days&#xD;
             before first dose of study drug&#xD;
&#xD;
          8. Women of child bearing potential and men with partners of child bearing potential must&#xD;
             agree to use effective contraception during therapy and for 4 months after completion&#xD;
             of therapy&#xD;
&#xD;
          9. Voluntary written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active infection other than HIV currently requiring systemic antimicrobial therapy&#xD;
&#xD;
          2. Previously treated on this study or received previous ALT-803&#xD;
&#xD;
          3. Latent TB infection or active TB disease prior to completing a standard regimen of&#xD;
             anti-TB therapy&#xD;
&#xD;
          4. Active fungal infection requiring systemic antifungal therapy&#xD;
&#xD;
          5. Active or recurrent herpes or varicella-zoster virus infection requiring treatment (or&#xD;
             chronic suppression)&#xD;
&#xD;
          6. Chronic hepatitis B or C&#xD;
&#xD;
          7. Planning or current pregnancy or breastfeeding&#xD;
&#xD;
          8. Intended modification of antiretroviral therapy in the next 24 weeks&#xD;
&#xD;
          9. NYHA (New York Heart Association) Class III or IV heart failure, uncontrollable&#xD;
             supraventricular arrhythmias, any history of a ventricular arrhythmia, or other&#xD;
             clinical signs of severe cardiac dysfunction&#xD;
&#xD;
         10. Symptomatic congestive heart failure, unstable angina pectoris, or Myocardial&#xD;
             infarction within 6 months prior to screening&#xD;
&#xD;
         11. Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval&#xD;
             greater than 500 milliseconds)&#xD;
&#xD;
         12. History or evidence of uncontrollable CNS disease&#xD;
&#xD;
         13. Prior organ allograft or allogeneic transplantation&#xD;
&#xD;
         14. On-going chronic systemic or regular inhaled corticosteroid use or other&#xD;
             immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible)&#xD;
&#xD;
         15. Psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
         16. Other illness that in the opinion of the investigator would exclude the patient from&#xD;
             participating in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim Schacker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>January 24, 2020</last_update_submitted>
  <last_update_submitted_qc>January 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>ART</keyword>
  <!-- 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/NCT02191098
org study id: 1508M77601-1
nct id: NCT02191098
lead sponsor: 
has dmc: Yes
To assess the safety and tolerability of ALT-803, as well as, the potential efficacy of
      ALT-803 in HIV
This is an open-label, single-arm intra-patient dose escalating pilot study of ALT-803, a
      recombinant human super agonist interleukin-15 (IL-15) complex with an expansion cohort at
      the maximum tolerated dose (MTD). The primary aim is to investigate the safety and
      tolerability of ALT-803 in HIV-infected people receiving potent and optimized antiretroviral
      therapy. All infusions will occur on a Monday. Subjects will be monitored for 24 hours after
      the first infusion and then for 6 hours after each subsequent infusion, provided no
      unacceptable toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assess the safety and tolerability of ALT-803 in HIV-infected subjects
time frame: 4 weeks
description: Safety and tolerability is determined by the incidence of adverse events, size of the inducible reservoir as estimated using the TILDA assay
measure: Assess the impact of ALT-803 on the size of the inducible reservoir,
time frame: 4 weeks
description: Assess the impact of ALT-803 on the size of the inducible reservoir, as estimated using the TILDA assay, in total CD4+ T cells and memory subsets
arm group label: ALT-803
arm group type: Experimental
description: ALT-803
intervention type: Drug
intervention name: ALT-803
description: Interleukin 15 (IL-15) is a common γ-chain cytokine that is related to interleukin-2 (IL-2) and is a critical factor for the development, proliferation, and activation of effector natural killer (NK) and CD8+ memory T cells
arm group label: ALT-803
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Tim Schacker, MD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor