<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/NCT03831945</url>
  </required_header>
  <id_info>
    <org_study_id>190048</org_study_id>
    <secondary_id>19-I-0048</secondary_id>
    <nct_id>NCT03831945</nct_id>
  </id_info>
  <brief_title>Combination Therapy With VRC01 and 10-1074 in HIV-Infected Individuals Undergoing Sequential Treatment Interruptions</brief_title>
  <official_title>An Exploratory Study of Combination Therapy With VRC-HIVMAB060-00-AB (VRC01) and 10-1074 in HIVInfected Individuals Undergoing Sequential Treatment Interruptions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      A daily drug combination can keep human immunodeficiency virus (HIV) levels low for a long&#xD;
      time. But if this combination antiretroviral therapy (ART) stops, HIV levels go back up.&#xD;
      People can also develop resistance or permanent side effects. Researchers want to see if 2&#xD;
      new drugs can help control HIV when a person is not on ART.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To see if VRC01 and 10-1074 are safe and control HIV when a person is not on ART.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults 18-65 with HIV&#xD;
&#xD;
      Design:&#xD;
&#xD;
      All participants must agree to practice safer sex. Those who can get pregnant will have a&#xD;
      pregnancy test every visit.&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
      Physical exam&#xD;
&#xD;
      Medicine review&#xD;
&#xD;
      Blood and urine tests&#xD;
&#xD;
      Some participants may need to change their HIV medicine for a brief period of time during the&#xD;
      study.&#xD;
&#xD;
      A few weeks later, participants will repeat screening tests and stop taking their HIV&#xD;
      medicines.&#xD;
&#xD;
      Interruption phase 1: Participants will have blood tests every 2 weeks, and repeat screening&#xD;
      tests every 4 weeks.&#xD;
&#xD;
      Treatment phase: Once their HIV reaches a certain level in the blood, participants will get&#xD;
      the 2 study drugs or a salt water placebo. They will not know which they get. Each substance&#xD;
      will be given through a thin tube in an arm vein for about 1 hour. Participants will restart&#xD;
      their HIV medicines and repeat screening tests every 4 weeks.&#xD;
&#xD;
      Interruption phase 2: Once the level of HIV in the blood becomes undetectable for 3 months,&#xD;
      participants will again stop taking their HIV medicines and have blood tests every 2 weeks to&#xD;
      monitor the level of HIV in the blood.&#xD;
&#xD;
      Participants will restart their medicines by week 24. They will start sooner if they have&#xD;
      certain symptoms or blood levels of HIV become too high. They will repeat most screening&#xD;
      tests 3 times over 24 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent advances in antibody cloning technologies have led to the development of a number of&#xD;
      highly potent and human immunodeficiency virus (HIV)-specific broadly neutralizing monoclonal&#xD;
      antibodies (bNAbs) from B cells of HIV-infected individuals. It has been shown that certain&#xD;
      bNAbs can prevent acquisition of the virus, suppress viral replication, delay and/or prevent&#xD;
      plasma viral rebound following treatment interruption in simian/human immunodeficiency virus&#xD;
      (SHIV)-infected animals. Preliminary data from clinical trials indicates that bNAbs may delay&#xD;
      plasma viral rebound following interruption of antiretroviral therapy (ART) and block&#xD;
      cell-to-cell transmission of laboratory-adapted HIV in vitro.&#xD;
&#xD;
      In the above studies, suppression of plasma viremia was dependent on maintaining neutralizing&#xD;
      serum levels of bNAbs via repeated intravenous (IV) infusions. A recent pre-clinical study in&#xD;
      an acute SHIV-macaque model suggests a limited course of passive immunotherapy with two bNAbs&#xD;
      (10-1074 and 3BNC117) given shortly after infection, can result in prolonged suppression of&#xD;
      plasma viremia that is not dependent on the continuous presence of the bNAbs18. Based on CD8+&#xD;
      T cell depletion studies, it appears that the prolonged suppression of plasma viremia&#xD;
      observed in these animals resulted from the induction of potent antiviral CD8+ T cell&#xD;
      immunity by the short course bNAb treatment. The mechanism by which bNAb therapy could induce&#xD;
      such a response is unclear but could involve the early formation of unique bNAb-SHIV immune&#xD;
      complexes that subsequently induce an effective and durable T cell response to the virus.&#xD;
&#xD;
      In light of these encouraging preclinical outcomes, it is of considerable interest to&#xD;
      investigate whether treatment with a single infusion of two bNAbs (VRC01 and 10-1074) which&#xD;
      target different epitopes of HIV gp120 (CD4 binding site and V3 glycan, respectively), during&#xD;
      transient plasma viremia can induce long-lasting anti-HIV immunity capable of controlling&#xD;
      plasma viremia in the absence of ART.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    unable to recruit due to COVID pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">April 4, 2019</start_date>
  <completion_date type="Actual">December 8, 2020</completion_date>
  <primary_completion_date type="Actual">December 8, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART</measure>
    <time_frame>From start of second Analytical Treatment Interruption (ATI) until up to 16 weeks</time_frame>
    <description>Number of days from start of the second analytical treatment interruption (ATI) until the subject meets criteria to restart Antiretroviral Therapy (ART) before Week 16 [a confirmed &gt;30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (&gt;40 copies/mL); a sustained (&gt;4weeks) HIV RNA level of &gt; 1000 copies/mL, or any HIV related symptoms or pregnancy.]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants With Grade 3 or Higher Related Adverse Events</measure>
    <time_frame>From the start of the initial infusion through follow-up phase week 24</time_frame>
    <description>Percent of participants with grade 3 or higher adverse events, including serious adverse events, that were probably or definitely related to study agent</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Single infusion of VRC01 and 10-1074</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single infusion of Normal Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single infusion of 100 mL and 250 mL of normal saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>VRC-HIVMAB060-00-AB (VRC01)</intervention_name>
    <description>VRC01 is a broadly neutralizing human mAb targeted against the HIV-1CD4 binding site. As single intravenous infusion of VRC01(40 mg/kg) plus10-1074 (30mg/kg) or placebo will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is &gt; or = 200 copies/mL.</description>
    <arm_group_label>Single infusion of VRC01 and 10-1074</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>10-1074</intervention_name>
    <description>10-1074 is a recombinant, fully human mAb of the IgG1 lambda isotype that specifically binds to the base of the V3 loop within HIV-1 envelope gp-120. A single intravenous infusion of VRC01 (40 mg/kg) plus 10-1074 (30 mg/kg) or placebo will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is &gt; or = 200 copies/mL.</description>
    <arm_group_label>Single infusion of VRC01 and 10-1074</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Normal Saline Placebo</intervention_name>
    <description>2 sequential infusions of normal saline placebo in matching volumes to antibody infusions will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is &gt; or = 200 copies/mL.</description>
    <arm_group_label>Single infusion of Normal Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. 18-65 years of age.&#xD;
&#xD;
               2. HIV-1 infection and clinically stable.&#xD;
&#xD;
               3. General good health and has an identified primary health care provider for&#xD;
                  medical management of HIV infection and is willing to maintain a relationship&#xD;
                  with a primary health care provider for medical management of HIV infection while&#xD;
                  participating in the study.&#xD;
&#xD;
               4. CD4+ T cell count &gt;450 cells/mm(3) at screening.&#xD;
&#xD;
               5. Documentation of continuous ART treatment with suppression of plasma viral level&#xD;
                  below the lower limit of quantification (LLOQ) for the assay used for greater&#xD;
                  than or equal to 2 years. Individuals with blips (i.e., detectable viral levels&#xD;
                  on ART) prior to screening may be included provided they satisfy the following&#xD;
                  criteria:&#xD;
&#xD;
                    1. The blips are &lt;400 copies/mL, and&#xD;
&#xD;
                    2. Succeeding viral levels return to levels below the limit of detection on&#xD;
                       subsequent testing.&#xD;
&#xD;
               6. Laboratory values within pre-defined limits at screening:&#xD;
&#xD;
                    1. Absolute neutrophil count &gt;1,000/mm(3).&#xD;
&#xD;
                    2. Hemoglobin levels &gt;10.0 g/dL for men and &gt;9.0 g/dL for women.&#xD;
&#xD;
                    3. Platelet count &gt;100,000/mm(3).&#xD;
&#xD;
                    4. Estimated or a measured glomerular filtration rate &gt;60 mL/min/1.73 m(2) as&#xD;
                       determined by the NIH Clinical Center (CC) laboratory.&#xD;
&#xD;
                    5. Aspartate aminotransferase (AST) and alanine transaminase (ALT) levels of&#xD;
                       &lt;2.5 times upper limit of normal (ULN), direct bilirubin within the normal&#xD;
                       range for the NIH CC laboratory.&#xD;
&#xD;
               7. Willingness to have samples stored for future research.&#xD;
&#xD;
               8. Willingness to undergo analytical treatment interruption (ATI)&#xD;
&#xD;
               9. Willingness for both male and female subjects to agree to use barrier protection&#xD;
                  methods or abstinence during the ATI phase of the study to decrease the risk of&#xD;
                  HIV transmission.&#xD;
&#xD;
        Reproductive Risks&#xD;
&#xD;
        Contraception: The effects of VRC01 and 10-1074 on the developing human fetus are unknown.&#xD;
        For this reason, men and women of childbearing potential must agree to use adequate&#xD;
        pregnancy prevention. This includes the use an effective method of contraception (i.e.&#xD;
        condom with spermicide, diaphragm with spermicide, hormone-eluting intrauterine device&#xD;
        (IUD), hormone-based contraceptive with condom) for the study duration. Subjects should&#xD;
        also agree to use a male or female condom while off ART. Pregnancy prevention must be&#xD;
        practiced continuously for the duration of study participation. Females of childbearing-age&#xD;
        must have a negative pregnancy test result prior to receiving the infusions of VRC01 and&#xD;
        10-1074/placebo. During the course of the study, if a female subject, or the partner of a&#xD;
        male subject suspects or in fact becomes pregnant, the affected subject should inform the&#xD;
        study staff immediately, as well as the woman s primary care physician.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen&#xD;
             (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test&#xD;
             for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for&#xD;
             HCV RNA are eligible.&#xD;
&#xD;
          2. HIV immunotherapy or HIV vaccine(s) received within 1 year prior to screening.&#xD;
&#xD;
          3. Any prior history of receiving 10-1074 or VRC01.&#xD;
&#xD;
          4. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza,&#xD;
             pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.&#xD;
&#xD;
          5. Receipt of other investigational study agent within 28 days of enrollment.&#xD;
&#xD;
          6. Any active malignancy that may require systemic chemotherapy or radiation therapy.&#xD;
&#xD;
          7. Systemic immunosuppressive medications received within 3 months prior to enrollment&#xD;
             (Exceptions: [1] corticosteroid nasal spray or inhaler; [2] topical corticosteroids&#xD;
             for mild, uncomplicated dermatitis; or [3] oral/parenteral corticosteroids&#xD;
             administered for non-chronic conditions not expected to recur [length of therapy less&#xD;
             than or equal to 10 days, with completion in greater than or equal to 30 days prior to&#xD;
             enrollment]).&#xD;
&#xD;
          8. History or other clinical evidence of:&#xD;
&#xD;
               1. Significant or unstable cardiac or cerebrovascular disease (e.g., angina,&#xD;
                  congestive heart failure, recent stroke or myocardial infarction).&#xD;
&#xD;
               2. Severe illness, malignancy, immunodeficiency other than HIV, or any other&#xD;
                  condition that, in the opinion of the investigator, would make the subject&#xD;
                  unsuitable for the study.&#xD;
&#xD;
          9. Active drug or alcohol use or any other pattern of behavior that, in the opinion of&#xD;
             the investigator, would interfere with adherence to study requirements.&#xD;
&#xD;
         10. Pregnancy or breast-feeding at time of screening.&#xD;
&#xD;
         11. Documented multiclass antiretroviral drug resistance that, in the judgment of the&#xD;
             investigator, would pose a risk of virologic failure should additional mutations&#xD;
             develop during the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael C Sneller, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2019-I-0048.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA. Early antibody therapy can induce long-lasting immunity to SHIV. Nature. 2017 Mar 23;543(7646):559-563. doi: 10.1038/nature21435. Epub 2017 Mar 13.</citation>
    <PMID>28289286</PMID>
  </reference>
  <reference>
    <citation>Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. doi: 10.1056/NEJMoa1608243. Epub 2016 Nov 9.</citation>
    <PMID>27959728</PMID>
  </reference>
  <reference>
    <citation>Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suarez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kummerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fatkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.</citation>
    <PMID>30258136</PMID>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <results_first_submitted>August 2, 2021</results_first_submitted>
  <results_first_submitted_qc>September 22, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 12, 2021</results_first_posted>
  <last_update_submitted>September 22, 2021</last_update_submitted>
  <last_update_submitted_qc>September 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV Therapy</keyword>
  <keyword>HIV Neutralizing Antibodies</keyword>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT03831945/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>27 subjects were consented to protocol. 20 subjects started the study. Five subjects enrolled but not randomized due to the coronavirus disease 2019 (COVID 19) pandemic; one subject was lost to follow-up after enrollment, and one subjects not randomized due to hospitalization.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Single Infusion of VRC01 and 10-1074</title>
          <description>Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
        </group>
        <group group_id="P2">
          <title>Single Infusion of Normal Saline</title>
          <description>Single infusion of 100 mL and 250 mL of normal saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Received study agent, never started second Analytical Treatment Interruption (ATI) due to COVID-19</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Received study agent, never started second analytical Treatment Interruption due to unprotected sex</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Received study agent, second analytical treatment interruption (ATI) ended early due to COVID-19</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Single Infusion of VRC01 and 10-1074</title>
          <description>Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
        </group>
        <group group_id="B2">
          <title>Single Infusion of Normal Saline</title>
          <description>Single infusion of 100 mL and 250 mL of normal saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART</title>
        <description>Number of days from start of the second analytical treatment interruption (ATI) until the subject meets criteria to restart Antiretroviral Therapy (ART) before Week 16 [a confirmed &gt;30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (&gt;40 copies/mL); a sustained (&gt;4weeks) HIV RNA level of &gt; 1000 copies/mL, or any HIV related symptoms or pregnancy.]</description>
        <time_frame>From start of second Analytical Treatment Interruption (ATI) until up to 16 weeks</time_frame>
        <population>The analyses included all subjects who completed the second analytical treatment interruption phase. Because of safety concerns that stopping treatment for HIV during the current COVID-19 pandemic could increase the risk of getting severe COVID-19, the study was halted before sufficient participants had enrolled and completed the second analytical treatment interruption to accurately determine primary outcome</population>
        <group_list>
          <group group_id="O1">
            <title>Single Infusion of VRC01 and 10-1074</title>
            <description>Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
          </group>
          <group group_id="O2">
            <title>Single Infusion of Normal Saline</title>
            <description>Single infusion of 100 mL and 250 mL of normal saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
          </group>
        </group_list>
        <measure>
          <title>Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART</title>
          <description>Number of days from start of the second analytical treatment interruption (ATI) until the subject meets criteria to restart Antiretroviral Therapy (ART) before Week 16 [a confirmed &gt;30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (&gt;40 copies/mL); a sustained (&gt;4weeks) HIV RNA level of &gt; 1000 copies/mL, or any HIV related symptoms or pregnancy.]</description>
          <population>The analyses included all subjects who completed the second analytical treatment interruption phase. Because of safety concerns that stopping treatment for HIV during the current COVID-19 pandemic could increase the risk of getting severe COVID-19, the study was halted before sufficient participants had enrolled and completed the second analytical treatment interruption to accurately determine primary outcome</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57" lower_limit="50.5" upper_limit="59"/>
                    <measurement group_id="O2" value="63" lower_limit="51.25" upper_limit="78.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants With Grade 3 or Higher Related Adverse Events</title>
        <description>Percent of participants with grade 3 or higher adverse events, including serious adverse events, that were probably or definitely related to study agent</description>
        <time_frame>From the start of the initial infusion through follow-up phase week 24</time_frame>
        <population>The analyses included all subjects who received at least one infusion of study agent</population>
        <group_list>
          <group group_id="O1">
            <title>Single Infusion of VRC01 and 10-1074</title>
            <description>Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
          </group>
          <group group_id="O2">
            <title>Single Infusion of Normal Saline</title>
            <description>Single infusion of 100 mL and 250 mL of normal saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants With Grade 3 or Higher Related Adverse Events</title>
          <description>Percent of participants with grade 3 or higher adverse events, including serious adverse events, that were probably or definitely related to study agent</description>
          <population>The analyses included all subjects who received at least one infusion of study agent</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>After administration of study agent through follow-up phase week 24</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Single Infusion of VRC01 and 10-1074</title>
          <description>Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
        </group>
        <group group_id="E2">
          <title>Single Infusion of Normal Saline</title>
          <description>Single infusion of 100 mL and 250 mL of normal saline when viral load is &gt;/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Salivary gland disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gonorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Syphilis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Echocardiogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>SARS-CoV-2 test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ageusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anosmia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Dental prosthesis user</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sneller, Michael</name_or_title>
      <organization>National Institute of Allergy and Infectious Diseases</organization>
      <phone>+1 301 496 0491</phone>
      <email>MSNELLER@niaid.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03831945
org study id: 190048
secondary id: 19-I-0048
nct id: NCT03831945
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      A daily drug combination can keep human immunodeficiency virus (HIV) levels low for a long
      time. But if this combination antiretroviral therapy (ART) stops, HIV levels go back up.
      People can also develop resistance or permanent side effects. Researchers want to see if 2
      new drugs can help control HIV when a person is not on ART.

      Objective:

      To see if VRC01 and 10-1074 are safe and control HIV when a person is not on ART.

      Eligibility:

      Adults 18-65 with HIV

      Design:

      All participants must agree to practice safer sex. Those who can get pregnant will have a
      pregnancy test every visit.

      Participants will be screened with:

      Physical exam

      Medicine review

      Blood and urine tests

      Some participants may need to change their HIV medicine for a brief period of time during the
      study.

      A few weeks later, participants will repeat screening tests and stop taking their HIV
      medicines.

      Interruption phase 1: Participants will have blood tests every 2 weeks, and repeat screening
      tests every 4 weeks.

      Treatment phase: Once their HIV reaches a certain level in the blood, participants will get
      the 2 study drugs or a salt water placebo. They will not know which they get. Each substance
      will be given through a thin tube in an arm vein for about 1 hour. Participants will restart
      their HIV medicines and repeat screening tests every 4 weeks.

      Interruption phase 2: Once the level of HIV in the blood becomes undetectable for 3 months,
      participants will again stop taking their HIV medicines and have blood tests every 2 weeks to
      monitor the level of HIV in the blood.

      Participants will restart their medicines by week 24. They will start sooner if they have
      certain symptoms or blood levels of HIV become too high. They will repeat most screening
      tests 3 times over 24 weeks.
Recent advances in antibody cloning technologies have led to the development of a number of
      highly potent and human immunodeficiency virus (HIV)-specific broadly neutralizing monoclonal
      antibodies (bNAbs) from B cells of HIV-infected individuals. It has been shown that certain
      bNAbs can prevent acquisition of the virus, suppress viral replication, delay and/or prevent
      plasma viral rebound following treatment interruption in simian/human immunodeficiency virus
      (SHIV)-infected animals. Preliminary data from clinical trials indicates that bNAbs may delay
      plasma viral rebound following interruption of antiretroviral therapy (ART) and block
      cell-to-cell transmission of laboratory-adapted HIV in vitro.

      In the above studies, suppression of plasma viremia was dependent on maintaining neutralizing
      serum levels of bNAbs via repeated intravenous (IV) infusions. A recent pre-clinical study in
      an acute SHIV-macaque model suggests a limited course of passive immunotherapy with two bNAbs
      (10-1074 and 3BNC117) given shortly after infection, can result in prolonged suppression of
      plasma viremia that is not dependent on the continuous presence of the bNAbs18. Based on CD8+
      T cell depletion studies, it appears that the prolonged suppression of plasma viremia
      observed in these animals resulted from the induction of potent antiviral CD8+ T cell
      immunity by the short course bNAb treatment. The mechanism by which bNAb therapy could induce
      such a response is unclear but could involve the early formation of unique bNAb-SHIV immune
      complexes that subsequently induce an effective and durable T cell response to the virus.

      In light of these encouraging preclinical outcomes, it is of considerable interest to
      investigate whether treatment with a single infusion of two bNAbs (VRC01 and 10-1074) which
      target different epitopes of HIV gp120 (CD4 binding site and V3 glycan, respectively), during
      transient plasma viremia can induce long-lasting anti-HIV immunity capable of controlling
      plasma viremia in the absence of ART.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART
time frame: From start of second Analytical Treatment Interruption (ATI) until up to 16 weeks
description: Number of days from start of the second analytical treatment interruption (ATI) until the subject meets criteria to restart Antiretroviral Therapy (ART) before Week 16 [a confirmed >30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (>40 copies/mL); a sustained (>4weeks) HIV RNA level of > 1000 copies/mL, or any HIV related symptoms or pregnancy.]
measure: Percent of Participants With Grade 3 or Higher Related Adverse Events
time frame: From the start of the initial infusion through follow-up phase week 24
description: Percent of participants with grade 3 or higher adverse events, including serious adverse events, that were probably or definitely related to study agent
arm group label: Single infusion of VRC01 and 10-1074
arm group type: Active Comparator
description: Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is >/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.
arm group label: Single infusion of Normal Saline
arm group type: Placebo Comparator
description: Single infusion of 100 mL and 250 mL of normal saline when viral load is >/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.
intervention type: Biological
intervention name: VRC-HIVMAB060-00-AB (VRC01)
description: VRC01 is a broadly neutralizing human mAb targeted against the HIV-1CD4 binding site. As single intravenous infusion of VRC01(40 mg/kg) plus10-1074 (30mg/kg) or placebo will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is > or = 200 copies/mL.
arm group label: Single infusion of VRC01 and 10-1074
intervention type: Biological
intervention name: 10-1074
description: 10-1074 is a recombinant, fully human mAb of the IgG1 lambda isotype that specifically binds to the base of the V3 loop within HIV-1 envelope gp-120. A single intravenous infusion of VRC01 (40 mg/kg) plus 10-1074 (30 mg/kg) or placebo will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is > or = 200 copies/mL.
arm group label: Single infusion of VRC01 and 10-1074
intervention type: Biological
intervention name: Normal Saline Placebo
description: 2 sequential infusions of normal saline placebo in matching volumes to antibody infusions will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is > or = 200 copies/mL.
arm group label: Single infusion of Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Michael C Sneller, M.D.
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2019-I-0048.html
description: NIH Clinical Center Detailed Web Page
citation: Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA. Early antibody therapy can induce long-lasting immunity to SHIV. Nature. 2017 Mar 23;543(7646):559-563. doi: 10.1038/nature21435. Epub 2017 Mar 13.
PMID: 28289286
citation: Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. doi: 10.1056/NEJMoa1608243. Epub 2016 Nov 9.
PMID: 27959728
citation: Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suarez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kummerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fatkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.
PMID: 30258136
responsible party type: Sponsor
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 