xml: <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/NCT06033209</url>
    </required_header>
    <id_info>
      <org_study_id>HVTN 144</org_study_id>
      <secondary_id>39021</secondary_id>
      <nct_id>NCT06033209</nct_id>
    </id_info>
    <brief_title>A Trial to Evaluate an HIV Envelope Trimer, N332-GT5 gp140, Adjuvanted With SMNP in Adult Participants Without HIV</brief_title>
    <official_title>A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of an HIV Envelope Trimer, N332-GT5 gp140, Adjuvanted With SMNP in Adult Participants Without HIV</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institutes of Health (NIH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
      <collaborator>
        <agency>Department of Health and Human Services</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
    </sponsors>
    <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        HVTN 144 is a phase 1 clinical trial to being conducted to evaluate the safety and&#xD;
        immunogenicity of an HIV envelope trimer, N332-GT5 gp140, adjuvanted with saponin/MPLA&#xD;
        nanoparticles (SMNP) in adult participants without HIV. The study aims to evaluate the safety&#xD;
        and tolerability of N332-GT5 gp140 adjuvanted with SMNP in adult volunteers without HIV and&#xD;
        in overall good health, including identifying a safe and tolerable dose, route, and schedule&#xD;
        of administration of the novel adjuvant SMNP. The study also aims to evaluate the induction&#xD;
        of BG18-class immunoglobulin G (IgG) B-cell responses in memory B cells by the study regimens&#xD;
        and compare the responses between the different groups.&#xD;
  &#xD;
        HVTN 144 will be conducted in 2 parts with 84 volunteers without HIV and in overall good&#xD;
        health, aged 18 to 55 years. The study duration is 22 months which includes 8 months for&#xD;
        enrollment, planned safety holds, follow-up, and Adverse Event of Special Interest (AESI)&#xD;
        health contact 1 year after last vaccination.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will evaluate the safety and immunogenicity of combining 2 FIH products: N332-GT5&#xD;
        gp140 HIV trimer protein adjuvanted with SMNP, co-administered as 2 bolus immunizations (week&#xD;
        0 and 8) or fractionated escalating dose prime (6 immunizations over 3 weeks) followed by&#xD;
        bolus immunization boost (week 10), via either subcutaneous (SC) route in the upper arm or&#xD;
        intramuscular (IM) route to the deltoid. N332-GT5 gp140 is based on the BG505 MD39&#xD;
        native-like trimer (NLT). The dose escalation study (Part A) will determine the maximum safe&#xD;
        dose, within our schema, of N332-GT5 gp140 and SMNP for 4 vaccination modalities: IM/bolus,&#xD;
        IM/fractionated escalating dose prime, SC/bolus, and SC/fractionated escalating dose prime. A&#xD;
        primary endpoint will be safety and tolerability. The trial will evaluate: (1) the concept of&#xD;
        generalized germline targeting for HCDR3-dominant bnAb precursors; (2) germline targeting for&#xD;
        V3-glycan (V3G)-specific BG18-class bnAbs; (3) establishing a safe and effective dose of SMNP&#xD;
        in humans; (4) immunogenicity of an HIV Env trimer adjuvanted with SMNP; and (5) ranking of&#xD;
        HIV trimer immune response magnitude and quality for bolus/IM, bolus/SC, and fractionated&#xD;
        escalating dose with one of either IM or SC.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 16, 2023</start_date>
    <completion_date type="Anticipated">June 28, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 28, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>The overall design of this trial involves 2 parts. In Part A, the goal is to establish the tolerability of both N332-GT5 and the SMNP adjuvant. This is a partially randomized design - Part A is nonrandomized, and Part B is randomized.</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Local reactogenicity signs and symptoms (solicited adverse events) will be collected</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Systemic reactogenicity signs and symptoms (solicited adverse events) will be collected</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Serious Adverse Events (SAEs) leading to early participant withdrawal or permanent discontinuation</measure>
      <time_frame>35 weeks and for 12 months following any receipt of study product</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Medically attended adverse events (MAAEs) leading to early participant withdrawal or permanent discontinuation</measure>
      <time_frame>35 weeks and for 12 months following any receipt of study product</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of AESIs leading to early participant withdrawal or permanent discontinuation</measure>
      <time_frame>35 weeks and for 12 months following any receipt of study product</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Adverse Events (AEs) leading to early participant withdrawal or permanent discontinuation</measure>
      <time_frame>35 weeks and for 12 months following any receipt of study product</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Comparison of number of reported/assessed local and systemic reactogenicity, SAE's and AESI's and medically attended adverse events at increasing doses of adjuvant at constant dose of N332-GT5 gp140</measure>
      <time_frame>35 weeks</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Frequency of BG18 epitope-specific B cells as determined by flow cytometry</measure>
      <time_frame>35 weeks</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Proportion of participants with BG18-class IgG memory B cells in peripheral blood mononuclear cell (PBMCs), measured by antigen-specific B-cell sorting, B-cell receptor (BCR) sequencing, and bioinformatic analysis</measure>
      <time_frame>35 weeks</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Frequency of BG18-class B cells among IgG memory B cells in PBMCs, measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis</measure>
      <time_frame>35 weeks</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with BG18-class IgG B cells, measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of BG18-class B cells among IgG B cells in germinal centers (GCs), measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Response rate of serum binding Ab responses to N332-GT5 gp140 and BG18 epitope on the trimer measured by binding antibody multiplex assay (BAMA)</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Magnitude of serum binding Ab responses to N332-GT5 gp140 and BG18 epitope on the trimer measured by binding antibody multiplex assay (BAMA)</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Response rate of serum neutralizing antibodies (nAbs) that neutralize pseudoviruses engineered to be sensitive to BG18-precursors</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of serum nAbs that neutralize pseudoviruses engineered to be sensitive to BG18-precursors</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of N332-GT5 gp140 trimer-specific B cells</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of BG18 sequences isolated postvaccination</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Magnitude of binding Abs measured by BAMA</measure>
      <time_frame>35 weeks</time_frame>
    </secondary_outcome>
    <number_of_arms>15</number_of_arms>
    <enrollment type="Anticipated">84</enrollment>
    <condition>HIV</condition>
    <arm_group>
      <arm_group_label>Part A Intramuscular (IM) safety with dose finding - Group 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A IM safety with dose finding - Group 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A IM safety with dose finding - Group 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A IM safety with dose finding - Group 4</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A IM safety with dose finding - Group 5</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A IM safety with dose finding - Group 6</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A Subcutaneous (SC) safety with dose finding - Group 7</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A SC safety with dose finding - Group 8</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A SC safety with dose finding - Group 9</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A SC safety with dose finding - Group 10</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A SC safety with dose finding - Group 11</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A SC safety with dose finding - Group 12</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B IM Immunogenicity - Group 13</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B SC Immunogenicity - Group 14</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B Immunogenicity - Group 15</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group 15 N332-GT5 gp140 with SMNP dose and route (SC or IM) is To Be Determined (TBD) based on groups 6 and 12 (Part A).</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>N332-GT5 gp140 (IM, Bolus)</intervention_name>
      <description>IM in the deltoid</description>
      <arm_group_label>Part A IM safety with dose finding - Group 2</arm_group_label>
      <arm_group_label>Part A IM safety with dose finding - Group 3</arm_group_label>
      <arm_group_label>Part A IM safety with dose finding - Group 4</arm_group_label>
      <arm_group_label>Part A IM safety with dose finding - Group 5</arm_group_label>
      <arm_group_label>Part A Intramuscular (IM) safety with dose finding - Group 1</arm_group_label>
      <arm_group_label>Part B IM Immunogenicity - Group 13</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>N332-GT5 gp140 (IM, Fractioned)</intervention_name>
      <description>IM in the deltoid, Fractionated escalating dose for prime</description>
      <arm_group_label>Part A IM safety with dose finding - Group 6</arm_group_label>
      <arm_group_label>Part B Immunogenicity - Group 15</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>N332-GT5 gp140 (SC, Bolus)</intervention_name>
      <description>SC in the upper arm</description>
      <arm_group_label>Part A SC safety with dose finding - Group 10</arm_group_label>
      <arm_group_label>Part A SC safety with dose finding - Group 11</arm_group_label>
      <arm_group_label>Part A SC safety with dose finding - Group 8</arm_group_label>
      <arm_group_label>Part A SC safety with dose finding - Group 9</arm_group_label>
      <arm_group_label>Part A Subcutaneous (SC) safety with dose finding - Group 7</arm_group_label>
      <arm_group_label>Part B SC Immunogenicity - Group 14</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>N332-GT5 gp140 (SC, Fractioned)</intervention_name>
      <description>SC in the upper arm, Fractionated escalating dose for prime</description>
      <arm_group_label>Part A SC safety with dose finding - Group 12</arm_group_label>
      <arm_group_label>Part B Immunogenicity - Group 15</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>SMNP (IM, Bolus)</intervention_name>
      <description>IM in the deltoid</description>
      <arm_group_label>Part A IM safety with dose finding - Group 2</arm_group_label>
      <arm_group_label>Part A IM safety with dose finding - Group 3</arm_group_label>
      <arm_group_label>Part A IM safety with dose finding - Group 4</arm_group_label>
      <arm_group_label>Part A IM safety with dose finding - Group 5</arm_group_label>
      <arm_group_label>Part A Intramuscular (IM) safety with dose finding - Group 1</arm_group_label>
      <arm_group_label>Part B IM Immunogenicity - Group 13</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>SMNP (IM, Fractioned)</intervention_name>
      <description>IM in the deltoid, Fractionated escalating dose for prime</description>
      <arm_group_label>Part A IM safety with dose finding - Group 6</arm_group_label>
      <arm_group_label>Part B Immunogenicity - Group 15</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>SMNP (SC, Bolus)</intervention_name>
      <description>SC in the upper arm</description>
      <arm_group_label>Part A SC safety with dose finding - Group 10</arm_group_label>
      <arm_group_label>Part A SC safety with dose finding - Group 11</arm_group_label>
      <arm_group_label>Part A SC safety with dose finding - Group 8</arm_group_label>
      <arm_group_label>Part A SC safety with dose finding - Group 9</arm_group_label>
      <arm_group_label>Part A Subcutaneous (SC) safety with dose finding - Group 7</arm_group_label>
      <arm_group_label>Part B SC Immunogenicity - Group 14</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>SMNP (SC, Fractioned)</intervention_name>
      <description>SC in the upper arm, Fractionated escalating dose for prime</description>
      <arm_group_label>Part A SC safety with dose finding - Group 12</arm_group_label>
      <arm_group_label>Part B Immunogenicity - Group 15</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          General and demographic criteria:&#xD;
  &#xD;
            1. Age of 18 through 55 years&#xD;
  &#xD;
            2. Access to a participating HVTN Clinical Research Site (CRS) and willingness to be&#xD;
               followed for the planned duration of the study&#xD;
  &#xD;
            3. Ability and willingness to provide informed consent&#xD;
  &#xD;
            4. Assessment of Understanding (AoU): Volunteer demonstrates understanding of this study&#xD;
               by completing a questionnaire prior to the first vaccination with verbal demonstration&#xD;
               of understanding of all questionnaire items answered incorrectly&#xD;
  &#xD;
            5. Agrees not to enroll in another study of an investigational research agent until&#xD;
               completion of the study&#xD;
  &#xD;
            6. Good general health as shown by medical history, physical exam, and screening&#xD;
               laboratory tests&#xD;
  &#xD;
               HIV-related criteria:&#xD;
  &#xD;
            7. Willingness to receive HIV test results&#xD;
  &#xD;
            8. Willingness to discuss HIV risks and amenable to HIV risk-reduction counseling&#xD;
  &#xD;
            9. Assessed by the clinic staff as having a low likelihood of acquiring HIV and is&#xD;
               committed to avoiding behaviors associated with a higher likelihood of acquiring HIV&#xD;
               through the last required protocol clinic visit&#xD;
  &#xD;
               Laboratory inclusion values Criteria:&#xD;
  &#xD;
           10. Hemoglobin (Hgb)&#xD;
  &#xD;
                 -  ≥ 11.0 g/dL for volunteers who were assigned female sex at birth (AFAB)&#xD;
  &#xD;
                 -  ≥ 13.0 g/dL for volunteers who were assigned male sex at birth (AMAB) and&#xD;
                    transgender men who have been on hormone therapy for more than 6 consecutive&#xD;
                    months&#xD;
  &#xD;
                 -  ≥ 12.0 g/dL for transgender women who have been on hormone therapy for more than&#xD;
                    6 consecutive months&#xD;
  &#xD;
                 -  For transgender volunteers who have been on hormone therapy for less than 6&#xD;
                    consecutive months, determine Hgb eligibility based on their sex assigned at&#xD;
                    birth&#xD;
  &#xD;
           11. White blood cell (WBC) count = 2500 to 12000 cells/mm3 with normal differential, or&#xD;
               differential approved by Investigator of Record (IoR) as not clinically significant&#xD;
  &#xD;
           12. Total lymphocyte count ≥ 650 cells/mm3 with normal differential, or differential&#xD;
               approved by IoR as not clinically significant&#xD;
  &#xD;
           13. Remaining differential either within local lab reference range or with site physician&#xD;
               approval&#xD;
  &#xD;
           14. Platelets = 125000 to 550000 cells/mm3&#xD;
  &#xD;
           15. Chemistry panel: Alanine aminotransferase (ALT) &lt; 1.25 times the institutional upper&#xD;
               limit of normal (ULN); serum creatinine ≤ 1.1 x ULN based on the local lab reference&#xD;
               range.&#xD;
  &#xD;
           16. Corrected total serum calcium level of ≥ 8.5 mg/dL&#xD;
  &#xD;
           17. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-approved&#xD;
               enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA)&#xD;
  &#xD;
           18. Negative Hepatitis B surface antigen (HBsAg)&#xD;
  &#xD;
           19. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV nucleic acid&#xD;
               test (NAT) if the anti-HCV is positive.&#xD;
  &#xD;
               Reproductive status criteria:&#xD;
  &#xD;
           20. For volunteers AFAB or intersex at birth and are capable of becoming pregnant&#xD;
               (hereafter referred to as &quot;persons of pregnancy potential&quot;):&#xD;
  &#xD;
                 -  Must agree to use effective means of contraception for sexual activity that could&#xD;
                    lead to pregnancy from at least 21 days prior to enrollment and 4 weeks after&#xD;
                    their last scheduled vaccination timepoint.&#xD;
  &#xD;
                 -  Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test&#xD;
                    (urine or serum) at screening (ie, prior to randomization, if applicable) and&#xD;
                    prior to study-product administration on the day of study-product administration.&#xD;
                    (Persons of pregnancy potential require a pregnancy test prior to injection 1 of&#xD;
                    the fractionated escalating dose series)&#xD;
  &#xD;
                 -  Persons who are NOT of pregnancy potential due to having undergone hysterectomy&#xD;
                    or bilateral oophorectomy (verified by medical records) or having reached&#xD;
                    menopause (no menses for 1 year) are not required to undergo pregnancy testing.&#xD;
  &#xD;
           21. AFAB volunteers or volunteers who were intersex at birth must also agree not to seek&#xD;
               pregnancy through alternative methods, such as oocyte retrieval, artificial&#xD;
               insemination or in vitro fertilization until after the last required protocol clinic&#xD;
               visit.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          General criteria:&#xD;
  &#xD;
            1. Blood products received within 120 days before first vaccination&#xD;
  &#xD;
            2. Investigational research agents received within 30 days before first vaccination&#xD;
  &#xD;
            3. Body mass index (BMI) ≥ 40, or BMI ≥ 35 with 2 or more of the following: Age &gt; 45,&#xD;
               systolic blood pressure &gt; 140 mm Hg, diastolic blood pressure &gt; 90 mm Hg, current&#xD;
               smoker, known hyperlipidemia&#xD;
  &#xD;
            4. Intent to participate in any other study that requires non-HVTN HIV Ab testing during&#xD;
               the planned duration of the HVTN 144 study&#xD;
  &#xD;
            5. Pregnant or breastfeeding&#xD;
  &#xD;
            6. Active duty and reserve US military personnel&#xD;
  &#xD;
               Vaccines and other injections criteria:&#xD;
  &#xD;
            7. 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 144 Protocol Safety Review Team&#xD;
               (PSRT) will determine eligibility on a case-by-case basis.&#xD;
  &#xD;
            8. Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational.&#xD;
               Exceptions may be made by the HVTN 144 PSRT on a case-by-case basis.&#xD;
  &#xD;
            9. Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine&#xD;
               trial. Exceptions may be made by the HVTN 144 PSRT for vaccines that have subsequently&#xD;
               undergone licensure by the FDA. For volunteers who have received control/placebo in an&#xD;
               experimental vaccine trial, the HVTN 144 PSRT will determine eligibility on a&#xD;
               case-by-case basis. For volunteers who have received an experimental vaccine(s) more&#xD;
               than 1 year ago, eligibility for enrollment will be determined by the HVTN 144 PSRT on&#xD;
               a case-by-case basis.&#xD;
  &#xD;
           10. Live attenuated vaccines received within 30 days before the first vaccination or&#xD;
               scheduled within 28 days after injection (eg, measles, mumps, and rubella (MMR); oral&#xD;
               polio vaccine (OPV); varicella; yellow fever; live attenuated influenza vaccine).&#xD;
               ACAM2000 vaccine &gt;28 days prior with a vaccination scab still present.&#xD;
  &#xD;
           11. Any vaccines that are not live attenuated vaccines and were received within 14 days&#xD;
               prior to the first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B). Please&#xD;
               note this includes incompetent vaccine such as the Jynneos vaccine for the prevention&#xD;
               of mpox disease.&#xD;
  &#xD;
           12. Allergy treatment with antigen injections within 30 days before the first vaccination&#xD;
               or that are scheduled within 14 days after the first vaccination&#xD;
  &#xD;
               Immune system criteria:&#xD;
  &#xD;
           13. Immunosuppressive medications received within 168 days before first vaccination (not&#xD;
               exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical&#xD;
               corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course&#xD;
               of oral/parenteral prednisone or equivalent at doses &lt; 60 mg/day and length of therapy&#xD;
               &lt; 11 days with completion at least 30 days prior to enrollment)&#xD;
  &#xD;
           14. Serious adverse reactions to vaccines or to vaccine components such as AS01B&#xD;
               (&quot;Shingrix&quot;) or Matrix M (Novovax CoV2373), including history of anaphylaxis and&#xD;
               related symptoms, such as hives, respiratory difficulty, angioedema, and/or abdominal&#xD;
               pain (not exclusionary: a volunteer who had a nonanaphylactic adverse reaction to&#xD;
               pertussis vaccine as a child).&#xD;
  &#xD;
           15. IgG received within 60 days before first vaccination (for mAbs, see criterion #8&#xD;
               above)&#xD;
  &#xD;
           16. Autoimmune disease, current or history (not exclusionary: mild, well-controlled&#xD;
               psoriasis)&#xD;
  &#xD;
           17. AESIs: Volunteers who currently have, or have a history of, any condition that could&#xD;
               be considered an AESI for the product(s) administered in this protocol.&#xD;
  &#xD;
           18. Immunodeficiency&#xD;
  &#xD;
               Clinically significant medical conditions criteria:&#xD;
  &#xD;
           19. 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;
           20. Any medical, occupational, or other condition that, in the judgment of the&#xD;
               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;
           21. 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;
           22. Current anti-tuberculosis (TB) prophylaxis or therapy&#xD;
  &#xD;
           23. Asthma exclusion criteria:&#xD;
  &#xD;
               Asthma is excluded if the participant has ANY of the following:&#xD;
  &#xD;
                 -  Required either oral or parenteral corticosteroids for an exacerbation 2 or more&#xD;
                    times within the past year; OR&#xD;
  &#xD;
                 -  Needed emergency care, urgent care, hospitalization, or intubation for an acute&#xD;
                    asthma exacerbation within the past year (eg, would NOT exclude individuals with&#xD;
                    asthma who meet all other criteria but sought urgent/emergent care solely for&#xD;
                    asthma medication refills or coexisting conditions unrelated to asthma); OR&#xD;
  &#xD;
                 -  Uses a short-acting rescue inhaler more than 2 days/week for acute asthma&#xD;
                    symptoms (ie, not for preventive treatment prior to athletic activity); OR&#xD;
  &#xD;
                 -  Uses medium- to high-dose inhaled corticosteroids (greater than 250 mcg&#xD;
                    fluticasone or therapeutic equivalent) or more than 1 medication for maintenance&#xD;
                    therapy daily. For example, potential participants taking long-acting&#xD;
                    bronchodilator/inhaled corticosteroid combinations for daily maintenance are&#xD;
                    excluded (note: maintenance monotherapy with cromolyn, leukotriene receptor&#xD;
                    antagonist, or theophylline is not exclusionary).&#xD;
  &#xD;
           24. Diabetes mellitus type 1 or type 2 (not exclusionary: type 2 cases controlled with&#xD;
               diet alone or a history of isolated gestational diabetes)&#xD;
  &#xD;
           25. Thyroidectomy, or thyroid disease requiring medication during the last 12 months (not&#xD;
               exclusionary: well-controlled non-autoimmune thyroid disease)&#xD;
  &#xD;
           26. Hypertension: The average systolic blood pressure between the screening visit and the&#xD;
               enrollment visit must be below 140 mmHg. The average diastolic blood pressure between&#xD;
               the screening visit and the enrollment visit must be below 90 mmHg. A single&#xD;
               measurement greater than or equal to 160 mmHg systolic or 100 mmHg diastolic during&#xD;
               the current study evaluation is exclusionary.&#xD;
  &#xD;
           27. Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring&#xD;
               special precautions)&#xD;
  &#xD;
           28. Malignancy (not exclusionary: volunteer who has had malignancy excised surgically and&#xD;
               who, in the investigator's estimation, has a reasonable assurance of sustained cure,&#xD;
               or who is unlikely to experience recurrence of malignancy during the period of the&#xD;
               study)&#xD;
  &#xD;
           29. Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer&#xD;
               has used medications in order to prevent or treat seizure(s) at any time within the&#xD;
               past 3 years.&#xD;
  &#xD;
           30. Asplenia: Any condition resulting in the absence of a functional spleen&#xD;
  &#xD;
           31. History of angioedema or anaphylaxis (not exclusionary: angioedema or anaphylaxis with&#xD;
               known trigger and no episodes within 5 years)&#xD;
  &#xD;
           32. History of generalized urticaria within past 5 years&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lindsey Baden</last_name>
      <role>Study Chair</role>
      <affiliation>Brigham and Women's Hospital</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>UCSF School of Medicine</name>
        <address>
          <city>San Francisco</city>
          <state>California</state>
          <zip>94102</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Hyman Scott, MD, MPH</last_name>
        <phone>628-217-7483</phone>
        <email>hyman.scott@sfdph.org</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Atlanta - Hope Clinic</name>
        <address>
          <city>Decatur</city>
          <state>Georgia</state>
          <zip>30030</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Srilatha Edupuganti, MD</last_name>
        <phone>404-712-1434</phone>
        <email>sedupug@emory.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Brigham &amp; Women's Hospital</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02115</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Stephen Walsh, MD</last_name>
        <phone>617-732-8881</phone>
        <email>swalsh@partners.org</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Columbia University Medical Center</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>100032</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Magdalena Sobieszczyk, BA, MD, MPH</last_name>
        <phone>212-305-7185</phone>
        <email>mes52@cumc.columbia.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>New York Blood Center</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Hong V. Tieu</last_name>
        <phone>212-570-3032</phone>
        <email>mbianco@nybc.org</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University of Rochester Medical Center</name>
        <address>
          <city>Rochester</city>
          <state>New York</state>
          <zip>14642</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Michael Keefer, MD</last_name>
        <phone>585-275-5871</phone>
        <email>michael_keefer@urmc.rochester.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University of Pennsylvania</name>
        <address>
          <city>Philadelphia</city>
          <state>Pennsylvania</state>
          <zip>19104</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Ian Frank, MD</last_name>
        <phone>215-746-7346</phone>
        <email>IFrank@pennmedicine.upenn.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Vanderbilt Institute for Infection, Immunology and Inflammation</name>
        <address>
          <city>Nashville</city>
          <state>Tennessee</state>
          <zip>37232-2582</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Spyros A. Kalamas, MD</last_name>
        <phone>615-322-8688</phone>
        <email>s.kalams@vumc.org</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06033209
  org study id: HVTN 144
  secondary id: 39021
  nct id: NCT06033209
  lead sponsor: 
  collaborator: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  HVTN 144 is a phase 1 clinical trial to being conducted to evaluate the safety and
        immunogenicity of an HIV envelope trimer, N332-GT5 gp140, adjuvanted with saponin/MPLA
        nanoparticles (SMNP) in adult participants without HIV. The study aims to evaluate the safety
        and tolerability of N332-GT5 gp140 adjuvanted with SMNP in adult volunteers without HIV and
        in overall good health, including identifying a safe and tolerable dose, route, and schedule
        of administration of the novel adjuvant SMNP. The study also aims to evaluate the induction
        of BG18-class immunoglobulin G (IgG) B-cell responses in memory B cells by the study regimens
        and compare the responses between the different groups.
  
        HVTN 144 will be conducted in 2 parts with 84 volunteers without HIV and in overall good
        health, aged 18 to 55 years. The study duration is 22 months which includes 8 months for
        enrollment, planned safety holds, follow-up, and Adverse Event of Special Interest (AESI)
        health contact 1 year after last vaccination.
  This study will evaluate the safety and immunogenicity of combining 2 FIH products: N332-GT5
        gp140 HIV trimer protein adjuvanted with SMNP, co-administered as 2 bolus immunizations (week
        0 and 8) or fractionated escalating dose prime (6 immunizations over 3 weeks) followed by
        bolus immunization boost (week 10), via either subcutaneous (SC) route in the upper arm or
        intramuscular (IM) route to the deltoid. N332-GT5 gp140 is based on the BG505 MD39
        native-like trimer (NLT). The dose escalation study (Part A) will determine the maximum safe
        dose, within our schema, of N332-GT5 gp140 and SMNP for 4 vaccination modalities: IM/bolus,
        IM/fractionated escalating dose prime, SC/bolus, and SC/fractionated escalating dose prime. A
        primary endpoint will be safety and tolerability. The trial will evaluate: (1) the concept of
        generalized germline targeting for HCDR3-dominant bnAb precursors; (2) germline targeting for
        V3-glycan (V3G)-specific BG18-class bnAbs; (3) establishing a safe and effective dose of SMNP
        in humans; (4) immunogenicity of an HIV Env trimer adjuvanted with SMNP; and (5) ranking of
        HIV trimer immune response magnitude and quality for bolus/IM, bolus/SC, and fractionated
        escalating dose with one of either IM or SC.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: The overall design of this trial involves 2 parts. In Part A, the goal is to establish the tolerability of both N332-GT5 and the SMNP adjuvant. This is a partially randomized design - Part A is nonrandomized, and Part B is randomized.
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Local reactogenicity signs and symptoms (solicited adverse events) will be collected
  time frame: Through study completion, an average of 1 year
  measure: Systemic reactogenicity signs and symptoms (solicited adverse events) will be collected
  time frame: Through study completion, an average of 1 year
  measure: Number of Serious Adverse Events (SAEs) leading to early participant withdrawal or permanent discontinuation
  time frame: 35 weeks and for 12 months following any receipt of study product
  measure: Number of Medically attended adverse events (MAAEs) leading to early participant withdrawal or permanent discontinuation
  time frame: 35 weeks and for 12 months following any receipt of study product
  measure: Number of AESIs leading to early participant withdrawal or permanent discontinuation
  time frame: 35 weeks and for 12 months following any receipt of study product
  measure: Number of Adverse Events (AEs) leading to early participant withdrawal or permanent discontinuation
  time frame: 35 weeks and for 12 months following any receipt of study product
  measure: Comparison of number of reported/assessed local and systemic reactogenicity, SAE's and AESI's and medically attended adverse events at increasing doses of adjuvant at constant dose of N332-GT5 gp140
  time frame: 35 weeks
  measure: Frequency of BG18 epitope-specific B cells as determined by flow cytometry
  time frame: 35 weeks
  measure: Proportion of participants with BG18-class IgG memory B cells in peripheral blood mononuclear cell (PBMCs), measured by antigen-specific B-cell sorting, B-cell receptor (BCR) sequencing, and bioinformatic analysis
  time frame: 35 weeks
  measure: Frequency of BG18-class B cells among IgG memory B cells in PBMCs, measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis
  time frame: 35 weeks
  measure: Proportion of participants with BG18-class IgG B cells, measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis
  time frame: 35 weeks
  measure: Frequency of BG18-class B cells among IgG B cells in germinal centers (GCs), measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis
  time frame: 35 weeks
  measure: Response rate of serum binding Ab responses to N332-GT5 gp140 and BG18 epitope on the trimer measured by binding antibody multiplex assay (BAMA)
  time frame: 35 weeks
  measure: Magnitude of serum binding Ab responses to N332-GT5 gp140 and BG18 epitope on the trimer measured by binding antibody multiplex assay (BAMA)
  time frame: 35 weeks
  measure: Response rate of serum neutralizing antibodies (nAbs) that neutralize pseudoviruses engineered to be sensitive to BG18-precursors
  time frame: 35 weeks
  measure: Concentration of serum nAbs that neutralize pseudoviruses engineered to be sensitive to BG18-precursors
  time frame: 35 weeks
  measure: Frequency of N332-GT5 gp140 trimer-specific B cells
  time frame: 35 weeks
  measure: Frequency of BG18 sequences isolated postvaccination
  time frame: 35 weeks
  measure: Magnitude of binding Abs measured by BAMA
  time frame: 35 weeks
  arm group label: Part A Intramuscular (IM) safety with dose finding - Group 1
  arm group type: Experimental
  arm group label: Part A IM safety with dose finding - Group 2
  arm group type: Experimental
  arm group label: Part A IM safety with dose finding - Group 3
  arm group type: Experimental
  arm group label: Part A IM safety with dose finding - Group 4
  arm group type: Experimental
  arm group label: Part A IM safety with dose finding - Group 5
  arm group type: Experimental
  arm group label: Part A IM safety with dose finding - Group 6
  arm group type: Experimental
  arm group label: Part A Subcutaneous (SC) safety with dose finding - Group 7
  arm group type: Experimental
  arm group label: Part A SC safety with dose finding - Group 8
  arm group type: Experimental
  arm group label: Part A SC safety with dose finding - Group 9
  arm group type: Experimental
  arm group label: Part A SC safety with dose finding - Group 10
  arm group type: Experimental
  arm group label: Part A SC safety with dose finding - Group 11
  arm group type: Experimental
  arm group label: Part A SC safety with dose finding - Group 12
  arm group type: Experimental
  arm group label: Part B IM Immunogenicity - Group 13
  arm group type: Experimental
  arm group label: Part B SC Immunogenicity - Group 14
  arm group type: Experimental
  arm group label: Part B Immunogenicity - Group 15
  arm group type: Experimental
  description: Group 15 N332-GT5 gp140 with SMNP dose and route (SC or IM) is To Be Determined (TBD) based on groups 6 and 12 (Part A).
  intervention type: Biological
  intervention name: N332-GT5 gp140 (IM, Bolus)
  description: IM in the deltoid
  arm group label: Part A IM safety with dose finding - Group 2
  arm group label: Part A IM safety with dose finding - Group 3
  arm group label: Part A IM safety with dose finding - Group 4
  arm group label: Part A IM safety with dose finding - Group 5
  arm group label: Part A Intramuscular (IM) safety with dose finding - Group 1
  arm group label: Part B IM Immunogenicity - Group 13
  intervention type: Biological
  intervention name: N332-GT5 gp140 (IM, Fractioned)
  description: IM in the deltoid, Fractionated escalating dose for prime
  arm group label: Part A IM safety with dose finding - Group 6
  arm group label: Part B Immunogenicity - Group 15
  intervention type: Biological
  intervention name: N332-GT5 gp140 (SC, Bolus)
  description: SC in the upper arm
  arm group label: Part A SC safety with dose finding - Group 10
  arm group label: Part A SC safety with dose finding - Group 11
  arm group label: Part A SC safety with dose finding - Group 8
  arm group label: Part A SC safety with dose finding - Group 9
  arm group label: Part A Subcutaneous (SC) safety with dose finding - Group 7
  arm group label: Part B SC Immunogenicity - Group 14
  intervention type: Biological
  intervention name: N332-GT5 gp140 (SC, Fractioned)
  description: SC in the upper arm, Fractionated escalating dose for prime
  arm group label: Part A SC safety with dose finding - Group 12
  arm group label: Part B Immunogenicity - Group 15
  intervention type: Biological
  intervention name: SMNP (IM, Bolus)
  description: IM in the deltoid
  arm group label: Part A IM safety with dose finding - Group 2
  arm group label: Part A IM safety with dose finding - Group 3
  arm group label: Part A IM safety with dose finding - Group 4
  arm group label: Part A IM safety with dose finding - Group 5
  arm group label: Part A Intramuscular (IM) safety with dose finding - Group 1
  arm group label: Part B IM Immunogenicity - Group 13
  intervention type: Biological
  intervention name: SMNP (IM, Fractioned)
  description: IM in the deltoid, Fractionated escalating dose for prime
  arm group label: Part A IM safety with dose finding - Group 6
  arm group label: Part B Immunogenicity - Group 15
  intervention type: Biological
  intervention name: SMNP (SC, Bolus)
  description: SC in the upper arm
  arm group label: Part A SC safety with dose finding - Group 10
  arm group label: Part A SC safety with dose finding - Group 11
  arm group label: Part A SC safety with dose finding - Group 8
  arm group label: Part A SC safety with dose finding - Group 9
  arm group label: Part A Subcutaneous (SC) safety with dose finding - Group 7
  arm group label: Part B SC Immunogenicity - Group 14
  intervention type: Biological
  intervention name: SMNP (SC, Fractioned)
  description: SC in the upper arm, Fractionated escalating dose for prime
  arm group label: Part A SC safety with dose finding - Group 12
  arm group label: Part B Immunogenicity - Group 15
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Lindsey Baden
  role: Study Chair
  affiliation: Brigham and Women's Hospital
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  sharing ipd: No