<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/NCT03787095</url>
  </required_header>
  <id_info>
    <org_study_id>ACTG A5370</org_study_id>
    <secondary_id>38399</secondary_id>
    <nct_id>NCT03787095</nct_id>
  </id_info>
  <brief_title>Safety and Immunotherapeutic Activity of an Anti-PD-1 Antibody (Cemiplimab) in Participants With HIV-1 on Suppressive cART</brief_title>
  <official_title>Safety and Immunotherapeutic Activity of an Anti-PD-1 Antibody (Cemiplimab) in Participants With HIV-1 on Suppressive cART: A Phase I/II, Double-blind, Placebo-controlled, Ascending Multiple Dose Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</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>
      The purpose of this study was to evaluate the safety and immunotherapeutic activity of an&#xD;
      anti-PD-1 antibody (cemiplimab) in participants with HIV-1 on suppressive combination&#xD;
      antiretroviral therapy (cART).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study evaluated the safety and immunotherapeutic activity of an anti-PD-1 antibody&#xD;
      (cemiplimab) in participants with HIV-1 on combination antiretroviral therapy (cART) who have&#xD;
      plasma less than the quantification limit of an FDA-approved assay and CD4+ T cell counts&#xD;
      ≥350/mm^3.&#xD;
&#xD;
      Participants were planned to be enrolled into three sequential dose-rising cohorts.&#xD;
      Participants in each cohort received infusions of either cemiplimab or placebo, with planned&#xD;
      administration at study entry (Day 0) and Week 6, for a total of two infusions. All&#xD;
      participants continued their non-study provided ART regimen. Enrollment in the second and&#xD;
      third cohorts would only open after all participants in the previous cohort had reached week&#xD;
      12 and an evaluation of safety outcomes established that it is safe to dose escalate.&#xD;
&#xD;
      Participants had screening and pre-entry visits and attended study visits on Day 0 and Weeks&#xD;
      1, 2, 4, 6, 7, 8, 10, 12, 16, 20, 24, 28, 36, and 48. Participants were followed for 48&#xD;
      weeks.&#xD;
&#xD;
      Due to observed adverse events which were deemed possibly related to study treatment in two&#xD;
      of four treated participants, the study was terminated and did not enroll further&#xD;
      participants. The two participants who had adverse events did not receive the second&#xD;
      infusion. The treated participants were followed for the planned 48 weeks, while the placebo&#xD;
      participant was not followed after a final study visit at week 7.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Stopped by monitoring committee recommendation due to adverse events&#xD;
  </why_stopped>
  <start_date type="Actual">August 13, 2019</start_date>
  <completion_date type="Actual">August 18, 2020</completion_date>
  <primary_completion_date type="Actual">August 18, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Count of Participants With a Grade &gt;=3 Adverse Event (AE) or Grade &gt;=1 Immune-related AE (irAE) Related to Study Treatment</measure>
    <time_frame>Study Entry through Week 48 or premature discontinuation</time_frame>
    <description>Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.&#xD;
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Count of Participants With a Grade &gt;=1 irAE Related to Study Treatment</measure>
    <time_frame>Study Entry through Week 48 or premature discontinuation</time_frame>
    <description>Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.&#xD;
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline</measure>
    <time_frame>Baseline through Week 12</time_frame>
    <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline</measure>
    <time_frame>Baseline through Week 12</time_frame>
    <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Polyfunctional Response of HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg, CD107a, IL-2, and Tumor Necrosis Factor Alpha (TNFa) From Baseline to Post-baseline</measure>
    <time_frame>Baseline through Week 12</time_frame>
    <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Polyfunctional response was defined as being positive for two or more cytokines. Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion</measure>
    <time_frame>Baseline through Week 12</time_frame>
    <description>Change evaluated from baseline (average of pre-entry and entry measures) to after the first dose (average of Weeks 2-6), and from baseline to after the second dose (average of Weeks 8-12). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Cemiplimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 0.3 mg/kg of cemiplimab, administered at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo, administered at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cemiplimab</intervention_name>
    <description>Administered as an intravenous (IV) infusion</description>
    <arm_group_label>Cohort 1: Cemiplimab</arm_group_label>
    <other_name>REGN2810</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Diluent for REGN2810, administered as an IV infusion</description>
    <arm_group_label>Cohort 1: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infection&#xD;
&#xD;
          -  On ART for at least 24 months&#xD;
&#xD;
          -  Receiving ART with no changes of the components of ART medications within 90 days&#xD;
             prior to study entry&#xD;
&#xD;
               -  Changes within drug class, in drug formulation or dose are allowed more than 30&#xD;
                  days prior to study entry.&#xD;
&#xD;
          -  CD4+ T cell count ≥350 cells/mm^3&#xD;
&#xD;
          -  At least two plasma HIV-1 RNA less than the quantification limit of an FDA-approved&#xD;
             assay within 18 months&#xD;
&#xD;
               -  A single detectable HIV-1 RNA but less than 1000 copies/mL is allowed if followed&#xD;
                  by HIV-1 RNA below quantifiable limits.&#xD;
&#xD;
          -  HIV-1 RNA level less than the quantification limit of an FDA-approved assay within 90&#xD;
             days prior to study entry&#xD;
&#xD;
          -  The following laboratory values within 90 days prior to entry:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥1500 cells/mm^3&#xD;
&#xD;
               -  Hemoglobin ≥14.0 g/dL for men and ≥12.0 g/dL for women&#xD;
&#xD;
               -  Platelet count ≥150,000/mm^3&#xD;
&#xD;
               -  Creatinine clearance ≥60 mL/min&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal&#xD;
                  limits&#xD;
&#xD;
               -  Normal thyroid, adrenal and diabetes testing&#xD;
&#xD;
          -  Negative tuberculosis (TB) test result, OR documentation of completed TB prophylaxis&#xD;
             treatment&#xD;
&#xD;
          -  HCV antibody negative result or, if HCV antibody positive, undetectable HCV RNA result&#xD;
&#xD;
          -  Negative HBsAg result&#xD;
&#xD;
          -  Ability and willingness to provide informed consent.&#xD;
&#xD;
          -  Ability and willingness to continue non-study-provided cART throughout the study.&#xD;
&#xD;
          -  Female participants must have a negative pregnancy test. Agree not to participate in a&#xD;
             conception process (e.g., active attempt to become pregnant or to impregnate, sperm&#xD;
             donation, in vitro fertilization, egg donation) during the study.&#xD;
&#xD;
          -  When participating in sexual activity that could lead to pregnancy, agree to use at&#xD;
             least two reliable forms of contraception simultaneously during the study through week&#xD;
             48.&#xD;
&#xD;
          -  Participants who are not of reproductive potential (women who have been&#xD;
             post-menopausal for at least 24 consecutive months or have undergone hysterectomy&#xD;
             and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia&#xD;
             or undergone vasectomy) are eligible without requiring the use of contraceptives.&#xD;
&#xD;
          -  Weight ≥50 kg (110 pounds)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of malignancy within the last 5 years.&#xD;
&#xD;
               -  Prior non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin&#xD;
                  cancer) is not exclusionary with documentation of complete resection at least 3&#xD;
                  months prior to enrollment.&#xD;
&#xD;
          -  HIV-related opportunistic infections within the last 5 years&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease (COPD).&#xD;
&#xD;
          -  Prior radiation therapy.&#xD;
&#xD;
          -  Active or previously treated active TB.&#xD;
&#xD;
          -  Active asthma requiring any treatment in the prior 2 years&#xD;
&#xD;
          -  Type I or type II diabetes mellitus.&#xD;
&#xD;
          -  History of or active autoimmune disorders including but not limited to inflammatory&#xD;
             bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis,&#xD;
             systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis,&#xD;
             adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis,&#xD;
             hypophysitis, or sarcoidosis.&#xD;
&#xD;
          -  Immune deficiency other than that caused by HIV infection.&#xD;
&#xD;
          -  Currently breastfeeding or pregnant.&#xD;
&#xD;
          -  Known allergy/sensitivity or any hypersensitivity to mAb-based biologics, cemiplimab&#xD;
             (anti-PD-1) or its formulation.&#xD;
&#xD;
          -  Active drug or alcohol use or dependence that, in the opinion of the site&#xD;
             investigator, would interfere with adherence to study requirements.&#xD;
&#xD;
          -  Receipt of investigational drug or use of investigational medical device within 6&#xD;
             months prior to study entry.&#xD;
&#xD;
          -  Use of or intent to use immunomodulators (e.g., interleukins, interferons,&#xD;
             cyclosporine, systemic corticosteroids exceeding physiologic doses), HIV vaccine, or&#xD;
             systemic cytotoxic chemotherapy within 60 days prior to study entry.&#xD;
&#xD;
               -  NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as&#xD;
                  prednisone ≤10 mg/day or the equivalent, will not be excluded. Stable physiologic&#xD;
                  glucocorticoid doses should not be discontinued for the duration of the study. In&#xD;
                  addition, participants receiving topical corticosteroids will not be excluded.&#xD;
&#xD;
          -  Any vaccination within 30 days&#xD;
&#xD;
          -  HCV treatment within 6 months&#xD;
&#xD;
          -  Prior immunoglobulin (IgG) therapy.&#xD;
&#xD;
          -  Current use or intent to use biotin ≥5 mg/day, including within dietary supplements.&#xD;
&#xD;
          -  History of chronic congestive heart failure or other significant cardiac conditions.&#xD;
&#xD;
          -  Any active, clinically significant medical condition that, in the opinion of the site&#xD;
             investigator, would place the participant at increased risk.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cynthia Gay, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Chapel Hill CRS</affiliation>
  </overall_official>
  <overall_official>
    <last_name>W. David Hardy, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alabama CRS</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSD Antiviral Research Center CRS</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chapel Hill CRS</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Puerto Rico</country>
  </removed_countries>
  <link>
    <url>https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables</url>
    <description>Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017</description>
  </link>
  <link>
    <url>http://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids</url>
    <description>Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010</description>
  </link>
  <link>
    <url>https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf</url>
    <description>National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0</description>
  </link>
  <results_reference>
    <citation>Gay CL, Bosch RJ, McKhann A, Moseley KF, Wimbish CL, Hendrickx SM, Messer M, Furlong M, Campbell DM, Jennings C, Benson C, Overton ET, Macatangay BJC, Kuritzkes DR, Miller E, Tressler R, Eron JJ, Hardy WD; A5370 Team. Suspected Immune-Related Adverse Events With an Anti-PD-1 Inhibitor in Otherwise Healthy People With HIV. J Acquir Immune Defic Syndr. 2021 Aug 15;87(5):e234-e236. doi: 10.1097/QAI.0000000000002716. No abstract available.</citation>
    <PMID>33929394</PMID>
  </results_reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <results_first_submitted>August 19, 2021</results_first_submitted>
  <results_first_submitted_qc>November 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 9, 2021</results_first_posted>
  <last_update_submitted>February 25, 2022</last_update_submitted>
  <last_update_submitted_qc>February 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cemiplimab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie results in the publication, after deidentification.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.</ipd_time_frame>
    <ipd_access_criteria>With whom?&#xD;
Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.&#xD;
For what types of analyses?&#xD;
To achieve aims in the proposal approved by the AIDS Clinical Trials Group.&#xD;
By what mechanism will data be made available?&#xD;
Researchers may submit a request for access to data using the AIDS Clinical Trials Group &quot;Data Request&quot; form at:https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.</ipd_access_criteria>
    <ipd_url>https://submit.mis.s-3.net/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03787095/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 30, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03787095/SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 2, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03787095/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The first participant was enrolled in August 2019. The final participant was enrolled in September 2019. The study was paused to accrual for emergency review by the study monitoring committee (SMC) in October 2019, followed by the decision to close the study later that month. Participants were recruited from 3 sites in the US.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Cemiplimab</title>
          <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
        </group>
        <group group_id="P2">
          <title>Cohort 1: Placebo</title>
          <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1">Participant had final visit at study week 7 in accordance with decision from team after the study was closed.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Cemiplimab</title>
          <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
        </group>
        <group group_id="B2">
          <title>Cohort 1: Placebo</title>
          <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Placebo: Diluent for REGN2810 , administered as an IV infusion</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="4"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" lower_limit="39" upper_limit="54"/>
                    <measurement group_id="B2" value="52" lower_limit="52" upper_limit="52"/>
                    <measurement group_id="B3" value="51" lower_limit="50" upper_limit="52"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <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="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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>
                  <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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CD4 Count</title>
          <units>cells/mm^3</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1151" lower_limit="720" upper_limit="1674"/>
                    <measurement group_id="B2" value="348" lower_limit="348" upper_limit="348"/>
                    <measurement group_id="B3" value="911" lower_limit="528" upper_limit="1391"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CD8 Count</title>
          <units>cells/mm^3</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1516" lower_limit="1188" upper_limit="1872"/>
                    <measurement group_id="B2" value="286" lower_limit="286" upper_limit="286"/>
                    <measurement group_id="B3" value="1508" lower_limit="867" upper_limit="1524"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CD4/CD8 ratio</title>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.90" lower_limit="0.62" upper_limit="0.98"/>
                    <measurement group_id="B2" value="1.22" lower_limit="1.22" upper_limit="1.22"/>
                    <measurement group_id="B3" value="0.91" lower_limit="0.88" upper_limit="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HIV-1 RNA</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;40 copies/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=40 copies/mL</title>
              <category_list>
                <category>
                  <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>Weight</title>
          <units>kilograms</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="88.8" lower_limit="77.3" upper_limit="98.3"/>
                    <measurement group_id="B2" value="101.0" lower_limit="101.0" upper_limit="101.0"/>
                    <measurement group_id="B3" value="90.7" lower_limit="86.9" upper_limit="101.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Count of Participants With a Grade &gt;=3 Adverse Event (AE) or Grade &gt;=1 Immune-related AE (irAE) Related to Study Treatment</title>
        <description>Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.&#xD;
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines</description>
        <time_frame>Study Entry through Week 48 or premature discontinuation</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Cemiplimab</title>
            <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants With a Grade &gt;=3 Adverse Event (AE) or Grade &gt;=1 Immune-related AE (irAE) Related to Study Treatment</title>
          <description>Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.&#xD;
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines</description>
          <population>All participants</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Count of Participants With a Grade &gt;=1 irAE Related to Study Treatment</title>
        <description>Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.&#xD;
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines</description>
        <time_frame>Study Entry through Week 48 or premature discontinuation</time_frame>
        <population>All participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Cemiplimab</title>
            <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants With a Grade &gt;=1 irAE Related to Study Treatment</title>
          <description>Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.&#xD;
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines</description>
          <population>All participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline</title>
        <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
        <time_frame>Baseline through Week 12</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Cemiplimab</title>
            <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen. Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline</title>
          <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
          <population>All participants</population>
          <units>Percentage of T cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.07"/>
                    <measurement group_id="O2" value="0.09" spread="NA">No standard deviation due to N=1</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: There is no change from baseline to post-baseline among participants treated with Cemiplimab. Per the analysis plan, only participants in the Cemiplimab arm are evaluated.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.71</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline</title>
        <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
        <time_frame>Baseline through Week 12</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Cemiplimab</title>
            <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen. Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline</title>
          <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
          <population>All participants</population>
          <units>Percentage of T cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.70"/>
                    <measurement group_id="O2" value="2.52" spread="NA">No standard deviation due to N=1</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: There is no change from baseline to post-baseline among participants treated with Cemiplimab. Per the analysis plan, only participants in the Cemiplimab arm are evaluated.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.00</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Polyfunctional Response of HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg, CD107a, IL-2, and Tumor Necrosis Factor Alpha (TNFa) From Baseline to Post-baseline</title>
        <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Polyfunctional response was defined as being positive for two or more cytokines. Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
        <time_frame>Baseline through Week 12</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Cemiplimab</title>
            <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen. Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Polyfunctional Response of HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg, CD107a, IL-2, and Tumor Necrosis Factor Alpha (TNFa) From Baseline to Post-baseline</title>
          <description>Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Polyfunctional response was defined as being positive for two or more cytokines. Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
          <population>All participants</population>
          <units>Percentage of T cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24" spread="0.42"/>
                    <measurement group_id="O2" value="-0.86" spread="NA">No standard deviation due to N=1</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: There is no change from baseline to post-baseline among participants treated with Cemiplimab. Per the analysis plan, only participants in the Cemiplimab arm are evaluated.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.33</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion</title>
        <description>Change evaluated from baseline (average of pre-entry and entry measures) to after the first dose (average of Weeks 2-6), and from baseline to after the second dose (average of Weeks 8-12). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
        <time_frame>Baseline through Week 12</time_frame>
        <population>As per the analysis plan, only participants who received two study treatment infusions (at baseline and week 6) of the study treatment Cemiplimab are included (therefore the Placebo arm is not listed). The two participants with adverse events only received one infusion at baseline and are not included.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Cemiplimab</title>
            <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion</title>
          <description>Change evaluated from baseline (average of pre-entry and entry measures) to after the first dose (average of Weeks 2-6), and from baseline to after the second dose (average of Weeks 8-12). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.</description>
          <population>As per the analysis plan, only participants who received two study treatment infusions (at baseline and week 6) of the study treatment Cemiplimab are included (therefore the Placebo arm is not listed). The two participants with adverse events only received one infusion at baseline and are not included.</population>
          <units>Percentage of T cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After first dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After second dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Study entry through week 48 or premature discontinuation.</time_frame>
      <desc>AEs were defined as using the following criteria: All Grade ≥1 AEs, all suspected or confirmed irAEs, all infusion reactions, all AEs that led to a change in study intervention, all AEs meeting SAE definition or Expedited Adverse Event (EAE) reporting requirement, and all targeted events as specified in the protocol.&#xD;
The DAIDS AE Grading Table, V2.1 was used. Infusion reactions, adrenal insufficiency, and pneumonitis were graded by CTCAE guidelines, v5.0.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: Cemiplimab</title>
          <description>Participants received 0.3 mg/kg of cemiplimab, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Cemiplimab: Administered as an intravenous (IV) infusion</description>
        </group>
        <group group_id="E2">
          <title>Cohort 1: Placebo</title>
          <description>Participants received placebo, with planned administration at Day 0 and Week 6 for a total of two infusions.&#xD;
Participants continued their current non-study provided ART regimen.&#xD;
Placebo: Diluent for REGN2810 , administered as an IV infusion</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</default_vocab>
        <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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Thyroiditis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood thyroid stimulating hormone decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Thyroxine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <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="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Drug-induced liver injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bicarbonate decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood phosphorus decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Creatinine renal clearance decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </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="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated early due to adverse events and was not able to fully evaluate the efficacy outcomes due to the small number of accrued participants.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>ACTG Clinicaltrials.gov Coordinator</name_or_title>
      <organization>ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company</organization>
      <phone>(301) 628-3348</phone>
      <email>ACTGCT.gov@fstrf.org</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/NCT03787095
org study id: ACTG A5370
secondary id: 38399
nct id: NCT03787095
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study was to evaluate the safety and immunotherapeutic activity of an
      anti-PD-1 antibody (cemiplimab) in participants with HIV-1 on suppressive combination
      antiretroviral therapy (cART).
This study evaluated the safety and immunotherapeutic activity of an anti-PD-1 antibody
      (cemiplimab) in participants with HIV-1 on combination antiretroviral therapy (cART) who have
      plasma less than the quantification limit of an FDA-approved assay and CD4+ T cell counts
      ≥350/mm^3.

      Participants were planned to be enrolled into three sequential dose-rising cohorts.
      Participants in each cohort received infusions of either cemiplimab or placebo, with planned
      administration at study entry (Day 0) and Week 6, for a total of two infusions. All
      participants continued their non-study provided ART regimen. Enrollment in the second and
      third cohorts would only open after all participants in the previous cohort had reached week
      12 and an evaluation of safety outcomes established that it is safe to dose escalate.

      Participants had screening and pre-entry visits and attended study visits on Day 0 and Weeks
      1, 2, 4, 6, 7, 8, 10, 12, 16, 20, 24, 28, 36, and 48. Participants were followed for 48
      weeks.

      Due to observed adverse events which were deemed possibly related to study treatment in two
      of four treated participants, the study was terminated and did not enroll further
      participants. The two participants who had adverse events did not receive the second
      infusion. The treated participants were followed for the planned 48 weeks, while the placebo
      participant was not followed after a final study visit at week 7.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Count of Participants With a Grade >=3 Adverse Event (AE) or Grade >=1 Immune-related AE (irAE) Related to Study Treatment
time frame: Study Entry through Week 48 or premature discontinuation
description: Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines
measure: Count of Participants With a Grade >=1 irAE Related to Study Treatment
time frame: Study Entry through Week 48 or premature discontinuation
description: Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism.
Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines
measure: Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline
time frame: Baseline through Week 12
description: Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.
measure: Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline
time frame: Baseline through Week 12
description: Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.
measure: Change in Polyfunctional Response of HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg, CD107a, IL-2, and Tumor Necrosis Factor Alpha (TNFa) From Baseline to Post-baseline
time frame: Baseline through Week 12
description: Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Polyfunctional response was defined as being positive for two or more cytokines. Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.
measure: Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion
time frame: Baseline through Week 12
description: Change evaluated from baseline (average of pre-entry and entry measures) to after the first dose (average of Weeks 2-6), and from baseline to after the second dose (average of Weeks 8-12). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.
arm group label: Cohort 1: Cemiplimab
arm group type: Experimental
description: Participants received 0.3 mg/kg of cemiplimab, administered at Day 0 and Week 6 for a total of two infusions.
Participants continued their current non-study provided ART regimen.
arm group label: Cohort 1: Placebo
arm group type: Placebo Comparator
description: Participants received placebo, administered at Day 0 and Week 6 for a total of two infusions.
Participants continued their current non-study provided ART regimen.
intervention type: Biological
intervention name: Cemiplimab
description: Administered as an intravenous (IV) infusion
arm group label: Cohort 1: Cemiplimab
other name: REGN2810
intervention type: Biological
intervention name: Placebo
description: Diluent for REGN2810, administered as an IV infusion
arm group label: Cohort 1: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Cynthia Gay, MD
role: Study Chair
affiliation: Chapel Hill CRS
last name: W. David Hardy, MD
role: Study Chair
affiliation: Johns Hopkins University
facility: 
facility: 
facility: 
country: United States
country: Puerto Rico
url: https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables
description: Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
url: http://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids
description: Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
url: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf
description: National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0
citation: Gay CL, Bosch RJ, McKhann A, Moseley KF, Wimbish CL, Hendrickx SM, Messer M, Furlong M, Campbell DM, Jennings C, Benson C, Overton ET, Macatangay BJC, Kuritzkes DR, Miller E, Tressler R, Eron JJ, Hardy WD; A5370 Team. Suspected Immune-Related Adverse Events With an Anti-PD-1 Inhibitor in Otherwise Healthy People With HIV. J Acquir Immune Defic Syndr. 2021 Aug 15;87(5):e234-e236. doi: 10.1097/QAI.0000000000002716. No abstract available.
PMID: 33929394
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Cemiplimab
sharing ipd: Yes
ipd description: Individual participant data that underlie results in the publication, after deidentification.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
ipd access criteria: With whom?
Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
For what types of analyses?
To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
By what mechanism will data be made available?
Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at:https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.
ipd url: https://submit.mis.s-3.net/
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated early due to adverse events and was not able to fully evaluate the efficacy outcomes due to the small number of accrued participants.
point of contact: 