<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/NCT03783130</url>
  </required_header>
  <id_info>
    <org_study_id>190031</org_study_id>
    <secondary_id>19-I-0031</secondary_id>
    <nct_id>NCT03783130</nct_id>
  </id_info>
  <brief_title>Dose, Safety, Tolerability, and Immunogenicity of an HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults</brief_title>
  <official_title>VRC 018: A Phase I Dose Escalation, Randomized, Open-Label Clinical Trial to Evaluate Dose, Safety, Tolerability and Immunogenicity of a HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults</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>
    <has_dmc>No</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>
      Background:&#xD;
&#xD;
      HIV stands for human immunodeficiency virus, which is the virus that causes AIDS. There is&#xD;
      currently no licensed vaccine to prevent HIV infection. Researchers want to test a vaccine&#xD;
      called Trimer 4571 for the first time. It was made at the National Institutes of Health (NIH)&#xD;
      and contains no HIV. The vaccine is mixed with a substance called alum and injected in the&#xD;
      arm. Alum is included to boost the body's immune response to the vaccine. It has been used in&#xD;
      licensed vaccines for over 60 years and has been found to be safe.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To see if the vaccine Trimer 4571 is safe, well-tolerated, and to study immune responses to&#xD;
      it.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Healthy adults ages 18-50 years&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants were screened with a physical exam and blood tests. They agreed to not become&#xD;
      pregnant and to avoid behavior that would put them at high-risk for HIV infection during the&#xD;
      study.&#xD;
&#xD;
      Participants had about 15 study visits over about 9 months.&#xD;
&#xD;
      The first 6 participants received a low dose of the vaccine mixed with alum.&#xD;
&#xD;
      Once the low dose was deemed safe, 10 new participants were allocated to receive a higher&#xD;
      dose.&#xD;
&#xD;
      All participants were randomly assigned to get the vaccine by injection in a muscle or under&#xD;
      the skin.&#xD;
&#xD;
      All participants received a total of 3 vaccine injections over 20 weeks. Each visit where&#xD;
      participants received the vaccine lasted about 5 hours. Participants were watched after each&#xD;
      injection. Participants who were able to get pregnant would have a pregnancy test before each&#xD;
      injection.&#xD;
&#xD;
      Participants received a thermometer and recorded their temperature and symptoms every day for&#xD;
      1 week after each injection. The injection site was checked for redness, swelling, or&#xD;
      bruising.&#xD;
&#xD;
      At follow-up visits, participants had blood drawn and checked for health changes or problems.&#xD;
      Follow up visits lasted about 1-2 hours.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design:&#xD;
&#xD;
      This is a Phase I, open-label, dose escalation study to evaluate the dose, safety,&#xD;
      tolerability, and immunogenicity of VRC-HIVRGP096-00-VP (Trimer 4571) with aluminum hydroxide&#xD;
      suspension (alum) as adjuvant in a three-injection regimen. The hypotheses were that the&#xD;
      vaccine will be safe and tolerable and will induce detectable immune responses. The primary&#xD;
      objective was to evaluate the safety and tolerability of the investigational vaccine at three&#xD;
      doses administered with alum. Secondary objectives were to evaluate humoral and cellular&#xD;
      immunogenicity of the investigational vaccine regimens.&#xD;
&#xD;
      Study Product:&#xD;
&#xD;
      VRC-HIVRGP096-00-VP (Trimer 4571) was developed by the Vaccine Research Center (VRC),&#xD;
      National Institute of Allergy and Infectious Diseases (NIAID). The soluble HIV-1 envelope&#xD;
      product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain&#xD;
      BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by&#xD;
      broadly neutralizing antibodies and resists gp120 conformational change caused by CD4&#xD;
      binding. Injections were administered intramuscularly (IM) and subcutaneously (SC) in a 1 mL&#xD;
      volume by needle and syringe. The product was provided at a 500 mcg/mL concentration in 3 mL&#xD;
      glass vials filled to 1.2 +/- 0.10 mL. Adjuvant is an aluminum hydroxide suspension (alum)&#xD;
      provided in a sterile, pyrogen-free suspension at a concentration of 5 mg/mL in 3 mL glass&#xD;
      vials filled to 0.7 +/- 0.10 mL.&#xD;
&#xD;
      Participants:&#xD;
&#xD;
      Healthy adults ages 18 to 50.&#xD;
&#xD;
      Study Plan:&#xD;
&#xD;
      Participants received VRC-HIVRGP096-00-VP at doses of 100 mcg or 500 mcg, both with 500 mcg&#xD;
      alum field mixed, administered via IM or SC injections. A dose escalation evaluation occurred&#xD;
      to ensure the safety data supported proceeding to the higher dose. Participants were&#xD;
      evaluated for safety and immune responses through blood collection at specified timepoints&#xD;
      throughout the study.&#xD;
&#xD;
      The study schema is below:&#xD;
&#xD;
      --------------------&#xD;
&#xD;
      Group 1: Participants = 3; Route = IM; Dose (mcg) = 100; Day** 0, Week** 8, Week** 20&#xD;
&#xD;
      Group 2: Participants = 3; Route = SC; Dose (mcg) = 100; Day** 0, Week** 8, Week** 20&#xD;
&#xD;
      Group 3: Participants = 5; Route = IM; Dose (mcg) = 500; Day** 0, Week** 8, Week** 20&#xD;
&#xD;
      Group 4: Participants = 5; Route = SC; Dose (mcg) = 500; Day** 0, Week** 8, Week** 20&#xD;
&#xD;
      Total = 16 Participants&#xD;
&#xD;
      **500 mcg of alum was mixed with Trimer 4571 for all groups&#xD;
&#xD;
      Duration:&#xD;
&#xD;
      Participants were followed for 40 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 7, 2019</start_date>
  <completion_date type="Actual">June 24, 2020</completion_date>
  <primary_completion_date type="Actual">June 24, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration</measure>
    <time_frame>7 days after study product administration, at approximately Week 1, Week 9 and Week 21</time_frame>
    <description>Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for &quot;Any Local Symptom&quot; is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration</measure>
    <time_frame>7 days after study product administration, at approximately Week 1, Week 9 and Week 21</time_frame>
    <description>Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for &quot;Any Systemic Symptom&quot; is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Measures of Safety</measure>
    <time_frame>Through 40 weeks after the first study product administration</time_frame>
    <description>Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Labs included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) with differential, creatine and ALT results were collected at screening, Day 0 prior to the first study product administration (baseline), and Weeks 1-2 after the 1st administration, Week 8 (2nd product administration), and Weeks 9-10 after the 2nd administration, Week 20 (3rd product administration), and Weeks 21-22 after the 3rd administration. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)</measure>
    <time_frame>Through 28 days after each study product administration, up to Week 24</time_frame>
    <description>Unsolicited AEs and attribution assessments were recorded in the study database from receipt of each study product administration through the visit scheduled at 28 days (or 4 weeks) after each study product administration. At other time periods greater than the 28-day (or 4-week) post product administration visit, only serious AEs (SAEs reported as a separate outcome and in the AE module), and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.&#xD;
If a participant had several AEs and some were evaluated as related and some as unrelated to study product, the participant is counted once as having the related event.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Serious Adverse Events (SAEs)</measure>
    <time_frame>Through 40 weeks after the first study product administration</time_frame>
    <description>SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 40. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antibody Response to Adjuvanted Trimer 4571 at 2 Weeks After the Final Study Product Administration</measure>
    <time_frame>Baseline through Study Week 22, at 14 days after the final study product administration.</time_frame>
    <description>Trimer 4571-specific antibody titers were measured by Electrochemiluminescence (ECLIA) using a Meso Scale Discovery (MSD) platform. Serum samples collected at baseline and at 2 weeks after the third product administration were tested in the assay. Since there is no standard/calibration curve available for interpolation of this raw response, area under the curve (AUC) was calculated for each serum sample tested in the 8-fold serial dilutions. The AUC measurement is calculated for each single timepoint sample (baseline or week 22, 2 weeks after the final vaccination). The AUC is calculated with Graphpad Prism™ using the trapezoid rule from the raw sample response (ECL response) over an 8-fold dilution series (Dilution Factor) for each sample. Group geometric mean AUCs and 95% Confidence Intervals are reported.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Human Immunodeficiency Virus Prevention</condition>
  <condition>Human Immunodeficiency Virus (HIV)</condition>
  <arm_group>
    <arm_group_label>Group 1: Trimer 4571 (100 mcg) IM with alum</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Trimer 4571 (100 mcg) SC with alum</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: Trimer 4571 (500 mcg) IM with alum</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: Trimer 4571 (500 mcg) SC with alum</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>VRC-HIVRGP096-00-VP</intervention_name>
    <description>Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.</description>
    <arm_group_label>Group 1: Trimer 4571 (100 mcg) IM with alum</arm_group_label>
    <arm_group_label>Group 2: Trimer 4571 (100 mcg) SC with alum</arm_group_label>
    <arm_group_label>Group 3: Trimer 4571 (500 mcg) IM with alum</arm_group_label>
    <arm_group_label>Group 4: Trimer 4571 (500 mcg) SC with alum</arm_group_label>
    <other_name>Trimer 4571</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Alum Adjuvant</intervention_name>
    <description>Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
    <arm_group_label>Group 1: Trimer 4571 (100 mcg) IM with alum</arm_group_label>
    <arm_group_label>Group 2: Trimer 4571 (100 mcg) SC with alum</arm_group_label>
    <arm_group_label>Group 3: Trimer 4571 (500 mcg) IM with alum</arm_group_label>
    <arm_group_label>Group 4: Trimer 4571 (500 mcg) SC with alum</arm_group_label>
    <other_name>Aluminum Hydroxide Suspension</other_name>
    <other_name>Alum</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        A participant must have met all of the following criteria:&#xD;
&#xD;
          1. Able and willing to complete the informed consent process.&#xD;
&#xD;
          2. 18-50 years old, inclusive, on day of enrollment.&#xD;
&#xD;
          3. Available for clinic follow-up through the last study visit.&#xD;
&#xD;
          4. Able to provide proof of identity to the satisfaction of the study clinician&#xD;
             completing the enrollment process.&#xD;
&#xD;
          5. Willing to donate blood for sample storage to be used for future research.&#xD;
&#xD;
          6. In good general health without clinically significant medical history.&#xD;
&#xD;
          7. Physical examination and laboratory results without clinically significant findings.&#xD;
&#xD;
          8. Body Mass Index (BMI) less than or equal to 40.&#xD;
&#xD;
          9. Assessed as low risk for human immunodeficiency virus (HIV) acquisition by agreeing to&#xD;
             discuss HIV infection risks, agreeing to risk reduction counseling, and agreeing to&#xD;
             avoid behavior associated with high risk of HIV exposure through the end of study.&#xD;
&#xD;
         10. Screening laboratory values within 56 days prior to enrollment that met the following&#xD;
             criteria:&#xD;
&#xD;
               -  Hemoglobin within the institutional normal limits&#xD;
&#xD;
               -  White blood cell (WBC) count between 2,500-12,000/mm^3&#xD;
&#xD;
               -  WBC differential absolute cell counts either within institutional normal range or&#xD;
                  accompanied by site Principal Investigator (PI) or Associate Investigator (AI)&#xD;
                  approval, except neutrophils and lymphocytes must specifically be within the&#xD;
                  range of greater than or equal to 0.75 x the lower limit of normal (LLN) and lees&#xD;
                  than or equal to 1.25 x the upper limit of normal (ULN) for neutrophil and&#xD;
                  lymphocyte absolute counts&#xD;
&#xD;
               -  Platelets = 125,000-500,000/m^3&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN based on the&#xD;
                  institutional normal range&#xD;
&#xD;
               -  Serum creatinine less than or equal to 1.1 x ULN based on the institutional&#xD;
                  normal range&#xD;
&#xD;
               -  Negative for HIV infection by an FDA approved method of detection&#xD;
&#xD;
             Woman-specific (if presumed to be of childbearing potential):&#xD;
&#xD;
         11. Agrees to use effective means of birth control from at least 21 days prior to&#xD;
             enrollment through the end of the study.&#xD;
&#xD;
         12. Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on&#xD;
             day of enrollment.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        A participant was excluded if one or more of the following conditions apply:&#xD;
&#xD;
        Woman-specific:&#xD;
&#xD;
          1. Breast-feeding or planning to become pregnant through the end of study.&#xD;
&#xD;
             Participant has received any of the following:&#xD;
&#xD;
          2. An investigational HIV vaccine.&#xD;
&#xD;
          3. Systemic glucocorticoid use equal or greater than prednisone 20mg/day within 4 weeks&#xD;
             prior to enrollment, or other medication use likely to impair vaccine response.&#xD;
&#xD;
          4. Blood products within 16 weeks prior to enrollment.&#xD;
&#xD;
          5. Live attenuated vaccines within 4 weeks prior to enrollment.&#xD;
&#xD;
          6. Inactivated vaccines within 2 weeks prior to enrollment.&#xD;
&#xD;
          7. Investigational research agents within 4 weeks prior to enrollment.&#xD;
&#xD;
          8. Current allergen immunotherapy with antigen injections, unless on maintenance&#xD;
             schedule.&#xD;
&#xD;
          9. Current anti-tuberculosis (TB) prophylaxis or therapy.&#xD;
&#xD;
             Participant had any of the following:&#xD;
&#xD;
         10. Serious reactions to vaccines that preclude receipt of study injections as determined&#xD;
             by the principal investigator or designee.&#xD;
&#xD;
         11. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.&#xD;
&#xD;
         12. Hypertension that is not well controlled.&#xD;
&#xD;
         13. Evidence of significant autoimmune disease or immunodeficiency.&#xD;
&#xD;
         14. Idiopathic urticaria within the past year.&#xD;
&#xD;
         15. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or&#xD;
             platelet disorder requiring special precautions) or significant bruising or bleeding&#xD;
             difficulties with IM injections or blood draws.&#xD;
&#xD;
         16. Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol&#xD;
             withdrawal more than 3 years ago, or 3) seizures that have not required treatment&#xD;
             within the last 3 years.&#xD;
&#xD;
         17. Asplenia or functional asplenia.&#xD;
&#xD;
         18. Any other chronic or clinically significant condition that in the opinion of the&#xD;
             investigator would jeopardize the safety or rights of the study subject including but&#xD;
             not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant&#xD;
             forms of: drug or alcohol abuse, asthma, psychiatric disorders, heart disease, or&#xD;
             cancer.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martin R Gaudinski, 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-0031.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, Kim HJ, Blattner C, de la Pena AT, Korzun J, Golabek M, de Los Reyes K, Ketas TJ, van Gils MJ, King CR, Wilson IA, Ward AB, Klasse PJ, Moore JP. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013 Sep;9(9):e1003618. doi: 10.1371/journal.ppat.1003618. Epub 2013 Sep 19.</citation>
    <PMID>24068931</PMID>
  </reference>
  <reference>
    <citation>Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Gorman J, Joyce MG, Guttman M, Ma X, Narpala S, Soto C, Terry DS, Yang Y, Zhou T, Ahlsen G, Bailer RT, Chambers M, Chuang GY, Doria-Rose NA, Druz A, Hallen MA, Harned A, Kirys T, Louder MK, O'Dell S, Ofek G, Osawa K, Prabhakaran M, Sastry M, Stewart-Jones GB, Stuckey J, Thomas PV, Tittley T, Williams C, Zhang B, Zhao H, Zhou Z, Donald BR, Lee LK, Zolla-Pazner S, Baxa U, Schon A, Freire E, Shapiro L, Lee KK, Arthos J, Munro JB, Blanchard SC, Mothes W, Binley JM, McDermott AB, Mascola JR, Kwong PD. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015 Jul;22(7):522-31. doi: 10.1038/nsmb.3051. Epub 2015 Jun 22.</citation>
    <PMID>26098315</PMID>
  </reference>
  <reference>
    <citation>Chuang GY, Geng H, Pancera M, Xu K, Cheng C, Acharya P, Chambers M, Druz A, Tsybovsky Y, Wanninger TG, Yang Y, Doria-Rose NA, Georgiev IS, Gorman J, Joyce MG, O'Dell S, Zhou T, McDermott AB, Mascola JR, Kwong PD. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J Virol. 2017 Apr 28;91(10):e02268-16. doi: 10.1128/JVI.02268-16. Print 2017 May 15.</citation>
    <PMID>28275193</PMID>
  </reference>
  <reference>
    <citation>U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. [July 2017]. Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf</citation>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <results_first_submitted>June 24, 2021</results_first_submitted>
  <results_first_submitted_qc>August 6, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 12, 2021</results_first_posted>
  <last_update_submitted>August 6, 2021</last_update_submitted>
  <last_update_submitted_qc>August 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Human Immunodeficiency Virus</keyword>
  <keyword>Immune Response</keyword>
  <keyword>Neutralizing Antibodies</keyword>
  <keyword>HIV Prevention</keyword>
  <keyword>Cellular Immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aluminum Hydroxide</mesh_term>
    <mesh_term>Aluminum sulfate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT03783130/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Healthy adults were recruited at the NIH Clinical Center in Bethesda, Maryland.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
          <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="P2">
          <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
          <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="P3">
          <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
          <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="P4">
          <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
          <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received All Product Administrations</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Population includes all enrolled participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
          <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="B2">
          <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
          <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="B3">
          <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
          <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="B4">
          <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
          <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="B5">
          <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="3"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.3" spread="12.7"/>
                    <measurement group_id="B2" value="35.7" spread="12.5"/>
                    <measurement group_id="B3" value="32.4" spread="8.1"/>
                    <measurement group_id="B4" value="32.4" spread="10.9"/>
                    <measurement group_id="B5" value="33.0" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>21-30 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>31-40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>41-50 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="6"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="15"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</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 group_id="B4" value="2"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiracial</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Under 18.5 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18.5-24.9 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25.0-29.9 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30.0 kg/m^2 or over</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration</title>
        <description>Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for &quot;Any Local Symptom&quot; is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.</description>
        <time_frame>7 days after study product administration, at approximately Week 1, Week 9 and Week 21</time_frame>
        <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O5">
            <title>Overall Incidence Trimer 4571 (100 mcg and 500 mcg)</title>
            <description>Trimer 4571 dose groups included adults who received either three doses of 100 mcg or three doses of 500 mcg of Trimer 4571 with 500 mcg of alum field mixed administered intramuscularly (IM), or administered subcutaneously (SC) on Day 0, Week 8, and Week 20</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration</title>
          <description>Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for &quot;Any Local Symptom&quot; is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.</description>
          <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</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="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pain/Tenderness</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Redness</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bruising</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Local Symptom</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration</title>
        <description>Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for &quot;Any Systemic Symptom&quot; is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.</description>
        <time_frame>7 days after study product administration, at approximately Week 1, Week 9 and Week 21</time_frame>
        <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O5">
            <title>Overall Incidence Trimer 4571 (100 mcg and 500 mcg)</title>
            <description>Trimer 4571 dose groups included adults who received either three doses of 100 mcg or three doses of 500 mcg of Trimer 4571 with 500 mcg of alum field mixed administered intramuscularly (IM), or administered subcutaneously (SC) on Day 0, Week 8, and Week 20</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration</title>
          <description>Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for &quot;Any Systemic Symptom&quot; is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.</description>
          <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</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="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Malaise</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Myalgia</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chills</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Systemic Symptom</title>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Abnormal Laboratory Measures of Safety</title>
        <description>Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Labs included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) with differential, creatine and ALT results were collected at screening, Day 0 prior to the first study product administration (baseline), and Weeks 1-2 after the 1st administration, Week 8 (2nd product administration), and Weeks 9-10 after the 2nd administration, Week 20 (3rd product administration), and Weeks 21-22 after the 3rd administration. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.</description>
        <time_frame>Through 40 weeks after the first study product administration</time_frame>
        <population>Population included all enrolled participants who had laboratory results available at any study visit post baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O5">
            <title>Overall Incidence Trimer 4571 (100 mcg and 500 mcg)</title>
            <description>Trimer 4571 dose groups included adults who received either three doses of 100 mcg or three doses of 500 mcg of Trimer 4571 with 500 mcg of alum field mixed administered intramuscularly (IM), or administered subcutaneously (SC) on Day 0, Week 8, and Week 20</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Laboratory Measures of Safety</title>
          <description>Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Labs included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) with differential, creatine and ALT results were collected at screening, Day 0 prior to the first study product administration (baseline), and Weeks 1-2 after the 1st administration, Week 8 (2nd product administration), and Weeks 9-10 after the 2nd administration, Week 20 (3rd product administration), and Weeks 21-22 after the 3rd administration. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.</description>
          <population>Population included all enrolled participants who had laboratory results available at any study visit post baseline.</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="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ALT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)</title>
        <description>Unsolicited AEs and attribution assessments were recorded in the study database from receipt of each study product administration through the visit scheduled at 28 days (or 4 weeks) after each study product administration. At other time periods greater than the 28-day (or 4-week) post product administration visit, only serious AEs (SAEs reported as a separate outcome and in the AE module), and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.&#xD;
If a participant had several AEs and some were evaluated as related and some as unrelated to study product, the participant is counted once as having the related event.</description>
        <time_frame>Through 28 days after each study product administration, up to Week 24</time_frame>
        <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O5">
            <title>Overall Incidence Trimer 4571 (100 mcg and 500 mcg)</title>
            <description>Trimer 4571 dose groups included adults who received either three doses of 100 mcg or three doses of 500 mcg of Trimer 4571 with 500 mcg of alum field mixed administered intramuscularly (IM), or administered subcutaneously (SC) on Day 0, Week 8, and Week 20</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)</title>
          <description>Unsolicited AEs and attribution assessments were recorded in the study database from receipt of each study product administration through the visit scheduled at 28 days (or 4 weeks) after each study product administration. At other time periods greater than the 28-day (or 4-week) post product administration visit, only serious AEs (SAEs reported as a separate outcome and in the AE module), and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.&#xD;
If a participant had several AEs and some were evaluated as related and some as unrelated to study product, the participant is counted once as having the related event.</description>
          <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</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="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Related to Study Product</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unrelated to Study Product</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Serious Adverse Events (SAEs)</title>
        <description>SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 40. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.</description>
        <time_frame>Through 40 weeks after the first study product administration</time_frame>
        <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O5">
            <title>Overall Incidence Trimer 4571 (100 mcg and 500 mcg)</title>
            <description>Trimer 4571 dose groups included adults who received either three doses of 100 mcg or three doses of 500 mcg of Trimer 4571 with 500 mcg of alum field mixed administered intramuscularly (IM), or administered subcutaneously (SC) on Day 0, Week 8, and Week 20</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious Adverse Events (SAEs)</title>
          <description>SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 40. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.</description>
          <population>Population included all enrolled participants who received at least one study product administration and provided safety data (via diary card and/or laboratory results) following study product administration. All participants completed the study product administration schedule per protocol.</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="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="16"/>
              </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 group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Antibody Response to Adjuvanted Trimer 4571 at 2 Weeks After the Final Study Product Administration</title>
        <description>Trimer 4571-specific antibody titers were measured by Electrochemiluminescence (ECLIA) using a Meso Scale Discovery (MSD) platform. Serum samples collected at baseline and at 2 weeks after the third product administration were tested in the assay. Since there is no standard/calibration curve available for interpolation of this raw response, area under the curve (AUC) was calculated for each serum sample tested in the 8-fold serial dilutions. The AUC measurement is calculated for each single timepoint sample (baseline or week 22, 2 weeks after the final vaccination). The AUC is calculated with Graphpad Prism™ using the trapezoid rule from the raw sample response (ECL response) over an 8-fold dilution series (Dilution Factor) for each sample. Group geometric mean AUCs and 95% Confidence Intervals are reported.</description>
        <time_frame>Baseline through Study Week 22, at 14 days after the final study product administration.</time_frame>
        <population>Population included all enrolled participants who received three study product administrations per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
            <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
          </group>
        </group_list>
        <measure>
          <title>Antibody Response to Adjuvanted Trimer 4571 at 2 Weeks After the Final Study Product Administration</title>
          <description>Trimer 4571-specific antibody titers were measured by Electrochemiluminescence (ECLIA) using a Meso Scale Discovery (MSD) platform. Serum samples collected at baseline and at 2 weeks after the third product administration were tested in the assay. Since there is no standard/calibration curve available for interpolation of this raw response, area under the curve (AUC) was calculated for each serum sample tested in the 8-fold serial dilutions. The AUC measurement is calculated for each single timepoint sample (baseline or week 22, 2 weeks after the final vaccination). The AUC is calculated with Graphpad Prism™ using the trapezoid rule from the raw sample response (ECL response) over an 8-fold dilution series (Dilution Factor) for each sample. Group geometric mean AUCs and 95% Confidence Intervals are reported.</description>
          <population>Population included all enrolled participants who received three study product administrations per protocol.</population>
          <units>AUC (ECL response units/Dilution Factor)</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Antibody Response at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81" lower_limit="40" upper_limit="163"/>
                    <measurement group_id="O2" value="53" lower_limit="17" upper_limit="169"/>
                    <measurement group_id="O3" value="62" lower_limit="25" upper_limit="151"/>
                    <measurement group_id="O4" value="50" lower_limit="26" upper_limit="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Antibody Response to Adjuvanted Trimer 4571 at 2 Weeks after the Final Study Product Administration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="674" lower_limit="50" upper_limit="9011"/>
                    <measurement group_id="O2" value="924" lower_limit="175" upper_limit="4880"/>
                    <measurement group_id="O3" value="2529" lower_limit="387" upper_limit="16515"/>
                    <measurement group_id="O4" value="1368" lower_limit="551" upper_limit="3397"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Solicited adverse events (AEs) were reported for 7 days after each study product administration. Unsolicited AEs were recorded from receipt of each study product administration through the visit scheduled at 28 days (or 4 weeks) after each study product administration. At other time periods greater than the 28-day (or 4-week) post product administration visit, only serious AEs and new chronic medical conditions that required ongoing medical management were recorded through the last study visit.</time_frame>
      <desc>All AEs recorded on the study were reported. Solicited AEs collected through systematic assessment and unsolicited AEs collected through non-systematic assessment are reported for participants who received study product and had safety data collected following the product administration. Data represent the number and percentage of participants experiencing the event. A participant with multiple experiences of the same event is counted once using the event of worst severity.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group 1: Trimer 4571 (100 mcg) IM With Alum</title>
          <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="E2">
          <title>Group 2: Trimer 4571 (100 mcg) SC With Alum</title>
          <description>Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="E3">
          <title>Group 3: Trimer 4571 (500 mcg) IM With Alum</title>
          <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
        <group group_id="E4">
          <title>Group 4: Trimer 4571 (500 mcg) SC With Alum</title>
          <description>Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20&#xD;
VRC-HIVRGP096-00-VP: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.&#xD;
Alum Adjuvant: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.</description>
        </group>
      </group_list>
      <serious_events>
        <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="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Non-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="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection Site Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Administration site pain</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Administration site swelling</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Administration site erythema</sub_title>
                <assessment>Systematic Assessment</assessment>
                <description>Redness</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
              </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="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ligament Rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </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>Martin Gaudinski, MD</name_or_title>
      <organization>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health</organization>
      <phone>301-451-8715</phone>
      <email>martin.gaudinski@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/NCT03783130
org study id: 190031
secondary id: 19-I-0031
nct id: NCT03783130
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

      HIV stands for human immunodeficiency virus, which is the virus that causes AIDS. There is
      currently no licensed vaccine to prevent HIV infection. Researchers want to test a vaccine
      called Trimer 4571 for the first time. It was made at the National Institutes of Health (NIH)
      and contains no HIV. The vaccine is mixed with a substance called alum and injected in the
      arm. Alum is included to boost the body's immune response to the vaccine. It has been used in
      licensed vaccines for over 60 years and has been found to be safe.

      Objectives:

      To see if the vaccine Trimer 4571 is safe, well-tolerated, and to study immune responses to
      it.

      Eligibility:

      Healthy adults ages 18-50 years

      Design:

      Participants were screened with a physical exam and blood tests. They agreed to not become
      pregnant and to avoid behavior that would put them at high-risk for HIV infection during the
      study.

      Participants had about 15 study visits over about 9 months.

      The first 6 participants received a low dose of the vaccine mixed with alum.

      Once the low dose was deemed safe, 10 new participants were allocated to receive a higher
      dose.

      All participants were randomly assigned to get the vaccine by injection in a muscle or under
      the skin.

      All participants received a total of 3 vaccine injections over 20 weeks. Each visit where
      participants received the vaccine lasted about 5 hours. Participants were watched after each
      injection. Participants who were able to get pregnant would have a pregnancy test before each
      injection.

      Participants received a thermometer and recorded their temperature and symptoms every day for
      1 week after each injection. The injection site was checked for redness, swelling, or
      bruising.

      At follow-up visits, participants had blood drawn and checked for health changes or problems.
      Follow up visits lasted about 1-2 hours.
Design:

      This is a Phase I, open-label, dose escalation study to evaluate the dose, safety,
      tolerability, and immunogenicity of VRC-HIVRGP096-00-VP (Trimer 4571) with aluminum hydroxide
      suspension (alum) as adjuvant in a three-injection regimen. The hypotheses were that the
      vaccine will be safe and tolerable and will induce detectable immune responses. The primary
      objective was to evaluate the safety and tolerability of the investigational vaccine at three
      doses administered with alum. Secondary objectives were to evaluate humoral and cellular
      immunogenicity of the investigational vaccine regimens.

      Study Product:

      VRC-HIVRGP096-00-VP (Trimer 4571) was developed by the Vaccine Research Center (VRC),
      National Institute of Allergy and Infectious Diseases (NIAID). The soluble HIV-1 envelope
      product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain
      BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by
      broadly neutralizing antibodies and resists gp120 conformational change caused by CD4
      binding. Injections were administered intramuscularly (IM) and subcutaneously (SC) in a 1 mL
      volume by needle and syringe. The product was provided at a 500 mcg/mL concentration in 3 mL
      glass vials filled to 1.2 +/- 0.10 mL. Adjuvant is an aluminum hydroxide suspension (alum)
      provided in a sterile, pyrogen-free suspension at a concentration of 5 mg/mL in 3 mL glass
      vials filled to 0.7 +/- 0.10 mL.

      Participants:

      Healthy adults ages 18 to 50.

      Study Plan:

      Participants received VRC-HIVRGP096-00-VP at doses of 100 mcg or 500 mcg, both with 500 mcg
      alum field mixed, administered via IM or SC injections. A dose escalation evaluation occurred
      to ensure the safety data supported proceeding to the higher dose. Participants were
      evaluated for safety and immune responses through blood collection at specified timepoints
      throughout the study.

      The study schema is below:

      --------------------

      Group 1: Participants = 3; Route = IM; Dose (mcg) = 100; Day** 0, Week** 8, Week** 20

      Group 2: Participants = 3; Route = SC; Dose (mcg) = 100; Day** 0, Week** 8, Week** 20

      Group 3: Participants = 5; Route = IM; Dose (mcg) = 500; Day** 0, Week** 8, Week** 20

      Group 4: Participants = 5; Route = SC; Dose (mcg) = 500; Day** 0, Week** 8, Week** 20

      Total = 16 Participants

      **500 mcg of alum was mixed with Trimer 4571 for all groups

      Duration:

      Participants were followed for 40 weeks.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
time frame: 7 days after study product administration, at approximately Week 1, Week 9 and Week 21
description: Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration
time frame: 7 days after study product administration, at approximately Week 1, Week 9 and Week 21
description: Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
measure: Number of Participants With Abnormal Laboratory Measures of Safety
time frame: Through 40 weeks after the first study product administration
description: Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Labs included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) with differential, creatine and ALT results were collected at screening, Day 0 prior to the first study product administration (baseline), and Weeks 1-2 after the 1st administration, Week 8 (2nd product administration), and Weeks 9-10 after the 2nd administration, Week 20 (3rd product administration), and Weeks 21-22 after the 3rd administration. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.
measure: Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)
time frame: Through 28 days after each study product administration, up to Week 24
description: Unsolicited AEs and attribution assessments were recorded in the study database from receipt of each study product administration through the visit scheduled at 28 days (or 4 weeks) after each study product administration. At other time periods greater than the 28-day (or 4-week) post product administration visit, only serious AEs (SAEs reported as a separate outcome and in the AE module), and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
If a participant had several AEs and some were evaluated as related and some as unrelated to study product, the participant is counted once as having the related event.
measure: Number of Participants With Serious Adverse Events (SAEs)
time frame: Through 40 weeks after the first study product administration
description: SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 40. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
measure: Antibody Response to Adjuvanted Trimer 4571 at 2 Weeks After the Final Study Product Administration
time frame: Baseline through Study Week 22, at 14 days after the final study product administration.
description: Trimer 4571-specific antibody titers were measured by Electrochemiluminescence (ECLIA) using a Meso Scale Discovery (MSD) platform. Serum samples collected at baseline and at 2 weeks after the third product administration were tested in the assay. Since there is no standard/calibration curve available for interpolation of this raw response, area under the curve (AUC) was calculated for each serum sample tested in the 8-fold serial dilutions. The AUC measurement is calculated for each single timepoint sample (baseline or week 22, 2 weeks after the final vaccination). The AUC is calculated with Graphpad Prism™ using the trapezoid rule from the raw sample response (ECL response) over an 8-fold dilution series (Dilution Factor) for each sample. Group geometric mean AUCs and 95% Confidence Intervals are reported.
arm group label: Group 1: Trimer 4571 (100 mcg) IM with alum
arm group type: Experimental
description: Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20
arm group label: Group 2: Trimer 4571 (100 mcg) SC with alum
arm group type: Experimental
description: Trimer 4571 injections (100 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20
arm group label: Group 3: Trimer 4571 (500 mcg) IM with alum
arm group type: Experimental
description: Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered intramuscularly (IM) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20
arm group label: Group 4: Trimer 4571 (500 mcg) SC with alum
arm group type: Experimental
description: Trimer 4571 injections (500 mcg), with 500 mcg of alum field mixed, administered subcutaneously (SC) in a 1 mL volume by Needle/Syringe on Day 0, Week 8, and Week 20
intervention type: Biological
intervention name: VRC-HIVRGP096-00-VP
description: Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.
arm group label: Group 1: Trimer 4571 (100 mcg) IM with alum
arm group label: Group 2: Trimer 4571 (100 mcg) SC with alum
arm group label: Group 3: Trimer 4571 (500 mcg) IM with alum
arm group label: Group 4: Trimer 4571 (500 mcg) SC with alum
other name: Trimer 4571
intervention type: Other
intervention name: Alum Adjuvant
description: Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.
arm group label: Group 1: Trimer 4571 (100 mcg) IM with alum
arm group label: Group 2: Trimer 4571 (100 mcg) SC with alum
arm group label: Group 3: Trimer 4571 (500 mcg) IM with alum
arm group label: Group 4: Trimer 4571 (500 mcg) SC with alum
other name: Aluminum Hydroxide Suspension
other name: Alum
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Martin R Gaudinski, 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-0031.html
description: NIH Clinical Center Detailed Web Page
citation: Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, Kim HJ, Blattner C, de la Pena AT, Korzun J, Golabek M, de Los Reyes K, Ketas TJ, van Gils MJ, King CR, Wilson IA, Ward AB, Klasse PJ, Moore JP. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013 Sep;9(9):e1003618. doi: 10.1371/journal.ppat.1003618. Epub 2013 Sep 19.
PMID: 24068931
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responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Immunologic Deficiency Syndromes
mesh term: Aluminum Hydroxide
mesh term: Aluminum sulfate
sharing ipd: No
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