<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/NCT02997969</url>
  </required_header>
  <id_info>
    <org_study_id>HVTN 111</org_study_id>
    <nct_id>NCT02997969</nct_id>
  </id_info>
  <brief_title>Safety and Immune Response to a Clade C DNA HIV Vaccine</brief_title>
  <acronym>HVTN111</acronym>
  <official_title>A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DNA and of MF59-adjuvanted Clade C Env Protein, in Healthy, HIV-uninfected Adult Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>HIV Vaccine Trials Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IPPOX Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Novartis Vaccines</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA&#xD;
      vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the safety, tolerability, and immunogenicity to DNA-HIV-PT123 (an&#xD;
      HIV clade C DNA vaccine) and to Bivalent Subtype C gp120/MF59 in healthy, HIV-uninfected&#xD;
      adults.&#xD;
&#xD;
      The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants&#xD;
      will be randomly assigned to one of 6 groups. Each group will receive experimental vaccine&#xD;
      and protein and/or placebo at 4 study visits. Participants in Groups 1-3 will receive all&#xD;
      injections via needle and syringe. Participants in Groups 4-6 will receive the DNA vaccine&#xD;
      via Biojector, and protein and/or placebo via needle and syringe.&#xD;
&#xD;
      Participants in Groups 1 and 4 will receive the DNA vaccine at months 0, 1, 3, and 6 and the&#xD;
      protein at months 3 and 6. Participants in Groups 2 and 5 will receive the DNA vaccine and&#xD;
      the protein at months 0, 1, and 6 and placebo at month 3. Participants in Groups 3 and 6 will&#xD;
      receive placebo at months 0, 1, 3, and 6.&#xD;
&#xD;
      Study visits will include a physical examination, an interview and/or questionnaire, HIV&#xD;
      testing and HIV risk-reduction counseling, and urine and blood collection. Participants may&#xD;
      optionally choose to provide rectal fluid, cervical fluid, or semen samples.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 21, 2016</start_date>
  <completion_date type="Actual">July 11, 2018</completion_date>
  <primary_completion_date type="Actual">July 11, 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)</measure>
    <time_frame>Measured through Month 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of adverse events (AEs)</measure>
    <time_frame>Measured through Month 12</time_frame>
    <description>By body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of serious adverse events (SAEs), adverse events of special interest (AESIs), and new chronic conditions (requiring medical intervention for 30 days or more)</measure>
    <time_frame>Measured through Month 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite of safety laboratory measures: white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), and creatinine</measure>
    <time_frame>Measured through Month 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration</measure>
    <time_frame>Measured through Month 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-specific total immunoglobulin G (IgG) binding antibody response breadth and magnitude as assessed by multiplex assay</measure>
    <time_frame>Measured through Month 6.5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Anti-V1/V2 scaffold IgG binding antibody responses as assessed by multiplex assay</measure>
    <time_frame>Measured through Month 6.5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of neutralizing antibody responses against HIV-1 isolates</measure>
    <time_frame>Measured through Month 6.5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-specific CD4+ T-cell responses as assessed by flow cytometry</measure>
    <time_frame>Measured through Month 6.5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-specific CD8+ T-cell responses as assessed by flow cytometry</measure>
    <time_frame>Measured through Month 6.5</time_frame>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">132</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Group 1: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6. All injections are via needle and syringe.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, and 6. They will receive placebo in both deltoids at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6. All injections are via needle and syringe.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo in both deltoids at months 0, 1, 3, and 6. All injections are via needle and syringe.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive the DNA-HIV-PT123 vaccine via Biojector in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6, via needle and syringe.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive the DNA-HIV-PT123 vaccine at months 0, 1, and 6, and placebo at month 3, in the left deltoid via Biojector. They will receive placebo at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6, in the right deltoid via needle and syringe.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo in the left deltoid via Biojector, and in the right deltoid via needle and syringe, at months 0, 1, 3, and 6.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DNA-HIV-PT123 vaccine</intervention_name>
    <description>Contains a mixture of 3 DNA plasmids in a 1:1:1 ratio, each at 1.33 mg: 1) clade C ZM96 gag, 2) clade C ZM96 gp140, and 3) clade C CN54 pol-nef, delivered at a total dose 4 mg administered as 1 mL intramuscularly (IM)</description>
    <arm_group_label>Group 1: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 2: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 4: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 5: DNA + Placebo + Protein/MF59</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Protein/MF59 vaccine</intervention_name>
    <description>clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered as 0.5 mL IM</description>
    <arm_group_label>Group 1: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 2: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 4: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 5: DNA + Placebo + Protein/MF59</arm_group_label>
    <other_name>Bivalent Subtype C gp120/MF59</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sodium Chloride, 0.9%, administered by IM injection at volumes to match the active products</description>
    <arm_group_label>Group 1: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 2: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 3: Placebo</arm_group_label>
    <arm_group_label>Group 4: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 5: DNA + Placebo + Protein/MF59</arm_group_label>
    <arm_group_label>Group 6: Placebo</arm_group_label>
    <other_name>Sodium Chloride, 0.9%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        General and Demographic Criteria&#xD;
&#xD;
          -  Age of 18 to 40 years&#xD;
&#xD;
          -  Access to a participating HVTN CRS and willingness to be followed for the planned&#xD;
             duration of the study&#xD;
&#xD;
          -  Ability and willingness to provide informed consent&#xD;
&#xD;
          -  Assessment of understanding: volunteer demonstrates understanding of this study;&#xD;
             provides answers to a questionnaire prior to first vaccination with verbal&#xD;
             demonstration of understanding of all questionnaire items answered incorrectly&#xD;
&#xD;
          -  Agrees not to enroll in another study of an investigational research agent&#xD;
&#xD;
          -  Good general health as shown by medical history, physical exam, and screening&#xD;
             laboratory tests&#xD;
&#xD;
        HIV-Related Criteria:&#xD;
&#xD;
          -  Willingness to receive HIV test results&#xD;
&#xD;
          -  Willingness to discuss HIV infection risks and amenable to HIV risk reduction&#xD;
             counseling.&#xD;
&#xD;
          -  Assessed by the clinic staff as being at &quot;low risk&quot; for HIV infection and committed to&#xD;
             maintaining behavior consistent with low risk of HIV exposure through the last&#xD;
             required protocol clinic visit.&#xD;
&#xD;
        Laboratory Inclusion Values:&#xD;
&#xD;
        Hemogram/Complete blood count (CBC)&#xD;
&#xD;
          -  Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers&#xD;
             who were born male&#xD;
&#xD;
          -  White blood cell count = 3,300 to 12,000 cells/mm^3&#xD;
&#xD;
          -  Total lymphocyte count ≥ 800 cells/mm^3&#xD;
&#xD;
          -  Remaining differential either within institutional normal range or with site physician&#xD;
             approval&#xD;
&#xD;
          -  Platelets = 125,000 to 550,000/mm^3 Chemistry&#xD;
&#xD;
          -  Chemistry panel: ALT, AST, and ALP &lt; 1.25 times the institutional upper limit of&#xD;
             normal; creatinine ≤ institutional upper limit of normal.&#xD;
&#xD;
        Virology&#xD;
&#xD;
          -  Negative HIV-1 and -2 blood test: Sites may use locally available assays that have&#xD;
             been approved by HVTN Laboratory Operations.&#xD;
&#xD;
          -  Negative Hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
          -  Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase&#xD;
             chain reaction (PCR) if the anti-HCV is positive Urine&#xD;
&#xD;
          -  Normal urine:&#xD;
&#xD;
               -  Negative urine glucose, and&#xD;
&#xD;
               -  Negative or trace urine protein, and&#xD;
&#xD;
               -  Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a&#xD;
                  microscopic urinalysis with red blood cells levels within institutional normal&#xD;
                  range).&#xD;
&#xD;
        Reproductive Status&#xD;
&#xD;
          -  Volunteers who were born female: negative serum or urine beta human chorionic&#xD;
             gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of&#xD;
             initial vaccination. Persons who are NOT of reproductive potential due to having&#xD;
             undergone total hysterectomy or bilateral oophorectomy (verified by medical records),&#xD;
             are not required to undergo pregnancy testing.&#xD;
&#xD;
        Reproductive status: A volunteer who was born female must:&#xD;
&#xD;
          -  Agree to consistently use effective contraception (Appendix B) for sexual activity&#xD;
             that could lead to pregnancy from at least 21 days prior to enrollment through the&#xD;
             last required protocol clinic visit.&#xD;
&#xD;
               -  Effective contraception is defined as using 1 of the following methods:&#xD;
&#xD;
               -  Condoms (male or female), or&#xD;
&#xD;
               -  Diaphragm or cervical cap,&#xD;
&#xD;
               -  PLUS 1 of the following methods:&#xD;
&#xD;
               -  Intrauterine device (IUD),&#xD;
&#xD;
               -  Hormonal contraception (in accordance with applicable national contraception&#xD;
                  guidelines),&#xD;
&#xD;
               -  Successful vasectomy in the male partner (considered successful if a volunteer&#xD;
                  reports that a male partner has [1] documentation of azoospermia by microscopy,&#xD;
                  or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite&#xD;
                  sexual activity after vasectomy); or&#xD;
&#xD;
               -  Any other contraceptive method approved by the HVTN 111 PSRT&#xD;
&#xD;
          -  Or not be of reproductive potential, such as having reached menopause (no menses for 1&#xD;
             year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;&#xD;
&#xD;
          -  Or be sexually abstinent. Volunteers who were born female must also agree not to seek&#xD;
             pregnancy through alternative methods, such as artificial insemination or in vitro&#xD;
             fertilization until after the last required protocol clinic visit Other Volunteers 21&#xD;
             years of age and older who were born female consenting to provide cervical samples:&#xD;
             pap smear within the 3 years prior to enrollment, with the latest result reported as&#xD;
             normal or ASCUS (atypical squamous cells of undetermined significance); for those 21&#xD;
             years and older that have not had a pap smear within the last 3 years prior to&#xD;
             enrollment, must be willing to undergo a pap smear with the result reported as normal&#xD;
             or ASCUS prior to sample collection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General&#xD;
&#xD;
          -  Blood products received within 120 days before first vaccination&#xD;
&#xD;
          -  Investigational research agents received within 30 days before first vaccination&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic&#xD;
             blood pressure &gt; 140 mm Hg, diastolic blood pressure &gt; 90 mm Hg, current smoker, known&#xD;
             hyperlipidemia&#xD;
&#xD;
          -  Intent to participate in another study of an investigational research agent during the&#xD;
             planned duration of the HVTN 111 study&#xD;
&#xD;
          -  Pregnant or breastfeeding Vaccines and other Injections&#xD;
&#xD;
          -  HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received&#xD;
             control/placebo in an HIV vaccine trial, the HVTN 111 PSRT will determine eligibility&#xD;
             on a case-by-case basis.&#xD;
&#xD;
          -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine&#xD;
             trial. Exceptions may be made for vaccines that have subsequently undergone licensure&#xD;
             by the FDA. For volunteers who have received control/placebo in an experimental&#xD;
             vaccine trial, the HVTN 111 PSRT will determine eligibility on a case-by-case basis.&#xD;
             For volunteers who have received an experimental vaccine(s) greater than 5 years ago,&#xD;
             eligibility for enrollment will be determined by the HVTN 111 PSRT on a case-by-case&#xD;
             basis.&#xD;
&#xD;
          -  Live attenuated vaccines other than influenza vaccine received within 30 days before&#xD;
             first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and&#xD;
             rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)&#xD;
&#xD;
          -  Influenza vaccine or any vaccines that are not live attenuated vaccines and were&#xD;
             received within 14 days prior to first vaccination (eg, tetanus, pneumococcal,&#xD;
             Hepatitis A or B)&#xD;
&#xD;
          -  Allergy treatment with antigen injections within 30 days before first vaccination or&#xD;
             that are scheduled within 14 days after first vaccination Immune System&#xD;
&#xD;
          -  Immunosuppressive medications received within 168 days before first vaccination. (Not&#xD;
             excluded from participation: [1] corticosteroid nasal spray; [2] inhaled&#xD;
             corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or&#xD;
             [4] a single course of oral/parenteral corticosteroids at doses &lt; 2 mg/kg/day and&#xD;
             length of therapy &lt; 11 days with completion at least 30 days prior to enrollment.&#xD;
&#xD;
          -  Serious adverse reactions to vaccines or to vaccine components such as eggs, egg&#xD;
             products, or neomycin, including history of anaphylaxis and related symptoms such as&#xD;
             hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a&#xD;
             volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)&#xD;
&#xD;
          -  Immunoglobulin received within 60 days before first vaccination&#xD;
&#xD;
          -  Autoimmune disease&#xD;
&#xD;
          -  Immunodeficiency Clinically significant medical conditions&#xD;
&#xD;
          -  Untreated or incompletely treated syphilis infection&#xD;
&#xD;
          -  Clinically significant medical condition, physical examination findings, clinically&#xD;
             significant abnormal laboratory results, or past medical history with clinically&#xD;
             significant implications for current health. A clinically significant condition or&#xD;
             process includes but is not limited to:&#xD;
&#xD;
               -  A process that would affect the immune response,&#xD;
&#xD;
               -  A process that would require medication that affects the immune response,&#xD;
&#xD;
               -  Any contraindication to repeated injections or blood draws,&#xD;
&#xD;
               -  A condition that requires active medical intervention or monitoring to avert&#xD;
                  grave danger to the volunteer's health or well-being during the study period,&#xD;
&#xD;
               -  A condition or process for which signs or symptoms could be confused with&#xD;
                  reactions to vaccine, or&#xD;
&#xD;
               -  Any condition specifically listed among the exclusion criteria below.&#xD;
&#xD;
          -  Any medical, psychiatric, occupational, or other condition that, in the judgment of&#xD;
             the investigator, would interfere with, or serve as a contraindication to, protocol&#xD;
             adherence, assessment of safety or reactogenicity, or a volunteer's ability to give&#xD;
             informed consent&#xD;
&#xD;
          -  Psychiatric condition that precludes compliance with the protocol. Specifically&#xD;
             excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,&#xD;
             or history of suicide attempt or gesture within the past 3 years.&#xD;
&#xD;
          -  Current anti-tuberculosis (TB) prophylaxis or therapy&#xD;
&#xD;
          -  Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as&#xD;
             defined in the most recent National Asthma Education and Prevention Program (NAEPP)&#xD;
             Expert Panel report). Exclude a volunteer who:&#xD;
&#xD;
               -  Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or&#xD;
&#xD;
               -  Uses moderate/high dose inhaled corticosteroids, or&#xD;
&#xD;
               -  In the past year has either of the following:&#xD;
&#xD;
                    -  Greater than 1 exacerbation of symptoms treated with oral/parenteral&#xD;
                       corticosteroids;&#xD;
&#xD;
                    -  Needed emergency care, urgent care, hospitalization, or intubation for&#xD;
                       asthma.&#xD;
&#xD;
          -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not&#xD;
             excluded: history of isolated gestational diabetes.)&#xD;
&#xD;
          -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months&#xD;
&#xD;
          -  Hypertension:&#xD;
&#xD;
               -  If a person has been found to have elevated blood pressure or hypertension during&#xD;
                  screening or previously, exclude for blood pressure that is not well controlled.&#xD;
                  Well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic&#xD;
                  and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief&#xD;
                  instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg&#xD;
                  diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and&#xD;
                  ≤ 90 mm Hg diastolic at enrollment.&#xD;
&#xD;
               -  If a person has NOT been found to have elevated blood pressure or hypertension&#xD;
                  during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg&#xD;
                  at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.&#xD;
&#xD;
          -  Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or&#xD;
             platelet disorder requiring special precautions)&#xD;
&#xD;
          -  Malignancy (Not excluded: Volunteer who has had malignancy excised surgically and who,&#xD;
             in the investigator's estimation, has a reasonable assurance of sustained cure. or who&#xD;
             is unlikely to experience recurrence of malignancy during the period of the study)&#xD;
&#xD;
          -  Seizure disorder: History of seizure(s) within past three years. Also exclude if&#xD;
             volunteer has used medications in order to prevent or treat seizure(s) at any time&#xD;
             within the past 3 years.&#xD;
&#xD;
          -  Asplenia: any condition resulting in the absence of a functional spleen&#xD;
&#xD;
          -  History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mina Hosseinipour</last_name>
    <role>Study Chair</role>
    <affiliation>UNC Project- Lilongwe</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aurum Tembisa CRS</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>1632</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isipingo CRS</name>
      <address>
        <city>Westville</city>
        <state>Kwa Zulu Natal</state>
        <zip>3630</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurum Institute Klerksdorp CRS</name>
      <address>
        <city>Klerksdorp</city>
        <state>North West Province</state>
        <zip>2571</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS</name>
      <address>
        <city>Mbeya</city>
        <country>Tanzania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Matero Reference Clinic CRS</name>
      <address>
        <city>Lusaka</city>
        <country>Zambia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
    <country>Tanzania</country>
    <country>Zambia</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>June 19, 2019</last_update_submitted>
  <last_update_submitted_qc>June 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
    <mesh_term>MF59 oil emulsion</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02997969
org study id: HVTN 111
nct id: NCT02997969
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA
      vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.
This study will evaluate the safety, tolerability, and immunogenicity to DNA-HIV-PT123 (an
      HIV clade C DNA vaccine) and to Bivalent Subtype C gp120/MF59 in healthy, HIV-uninfected
      adults.

      The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants
      will be randomly assigned to one of 6 groups. Each group will receive experimental vaccine
      and protein and/or placebo at 4 study visits. Participants in Groups 1-3 will receive all
      injections via needle and syringe. Participants in Groups 4-6 will receive the DNA vaccine
      via Biojector, and protein and/or placebo via needle and syringe.

      Participants in Groups 1 and 4 will receive the DNA vaccine at months 0, 1, 3, and 6 and the
      protein at months 3 and 6. Participants in Groups 2 and 5 will receive the DNA vaccine and
      the protein at months 0, 1, and 6 and placebo at month 3. Participants in Groups 3 and 6 will
      receive placebo at months 0, 1, 3, and 6.

      Study visits will include a physical examination, an interview and/or questionnaire, HIV
      testing and HIV risk-reduction counseling, and urine and blood collection. Participants may
      optionally choose to provide rectal fluid, cervical fluid, or semen samples.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)
time frame: Measured through Month 12
measure: Frequency of adverse events (AEs)
time frame: Measured through Month 12
description: By body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
measure: Frequency of serious adverse events (SAEs), adverse events of special interest (AESIs), and new chronic conditions (requiring medical intervention for 30 days or more)
time frame: Measured through Month 12
measure: Composite of safety laboratory measures: white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), and creatinine
time frame: Measured through Month 12
measure: Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration
time frame: Measured through Month 12
measure: HIV-specific total immunoglobulin G (IgG) binding antibody response breadth and magnitude as assessed by multiplex assay
time frame: Measured through Month 6.5
measure: Anti-V1/V2 scaffold IgG binding antibody responses as assessed by multiplex assay
time frame: Measured through Month 6.5
measure: Presence of neutralizing antibody responses against HIV-1 isolates
time frame: Measured through Month 6.5
measure: HIV-specific CD4+ T-cell responses as assessed by flow cytometry
time frame: Measured through Month 6.5
measure: HIV-specific CD8+ T-cell responses as assessed by flow cytometry
time frame: Measured through Month 6.5
arm group label: Group 1: DNA + Placebo + Protein/MF59
arm group type: Active Comparator
description: Participants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6. All injections are via needle and syringe.
arm group label: Group 2: DNA + Placebo + Protein/MF59
arm group type: Active Comparator
description: Participants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, and 6. They will receive placebo in both deltoids at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6. All injections are via needle and syringe.
arm group label: Group 3: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo in both deltoids at months 0, 1, 3, and 6. All injections are via needle and syringe.
arm group label: Group 4: DNA + Placebo + Protein/MF59
arm group type: Active Comparator
description: Participants will receive the DNA-HIV-PT123 vaccine via Biojector in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6, via needle and syringe.
arm group label: Group 5: DNA + Placebo + Protein/MF59
arm group type: Active Comparator
description: Participants will receive the DNA-HIV-PT123 vaccine at months 0, 1, and 6, and placebo at month 3, in the left deltoid via Biojector. They will receive placebo at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6, in the right deltoid via needle and syringe.
arm group label: Group 6: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo in the left deltoid via Biojector, and in the right deltoid via needle and syringe, at months 0, 1, 3, and 6.
intervention type: Biological
intervention name: DNA-HIV-PT123 vaccine
description: Contains a mixture of 3 DNA plasmids in a 1:1:1 ratio, each at 1.33 mg: 1) clade C ZM96 gag, 2) clade C ZM96 gp140, and 3) clade C CN54 pol-nef, delivered at a total dose 4 mg administered as 1 mL intramuscularly (IM)
arm group label: Group 1: DNA + Placebo + Protein/MF59
arm group label: Group 2: DNA + Placebo + Protein/MF59
arm group label: Group 4: DNA + Placebo + Protein/MF59
arm group label: Group 5: DNA + Placebo + Protein/MF59
intervention type: Biological
intervention name: Protein/MF59 vaccine
description: clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered as 0.5 mL IM
arm group label: Group 1: DNA + Placebo + Protein/MF59
arm group label: Group 2: DNA + Placebo + Protein/MF59
arm group label: Group 4: DNA + Placebo + Protein/MF59
arm group label: Group 5: DNA + Placebo + Protein/MF59
other name: Bivalent Subtype C gp120/MF59
intervention type: Biological
intervention name: Placebo
description: Sodium Chloride, 0.9%, administered by IM injection at volumes to match the active products
arm group label: Group 1: DNA + Placebo + Protein/MF59
arm group label: Group 2: DNA + Placebo + Protein/MF59
arm group label: Group 3: Placebo
arm group label: Group 4: DNA + Placebo + Protein/MF59
arm group label: Group 5: DNA + Placebo + Protein/MF59
arm group label: Group 6: Placebo
other name: Sodium Chloride, 0.9%
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mina Hosseinipour
role: Study Chair
affiliation: UNC Project- Lilongwe
facility: 
facility: 
facility: 
facility: 
facility: 
country: South Africa
country: Tanzania
country: Zambia
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Vaccines
mesh term: MF59 oil emulsion
sharing ipd: No