<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/NCT03254277</url>
  </required_header>
  <id_info>
    <org_study_id>YCO-0946</org_study_id>
    <nct_id>NCT03254277</nct_id>
  </id_info>
  <brief_title>3BNC117-LS First-in-Human Phase 1 Study</brief_title>
  <official_title>A Phase 1 First-in-human Study of the Safety and Pharmacokinetics of 3BNC117-LS in HIV-infected and HIV-uninfected Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rockefeller University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rockefeller University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed study is a phase 1 study of the mAb 3BNC117-LS administered intravenously in HIV&#xD;
      uninfected individuals and HIV-infected individuals, and subcutaneously in HIV-uninfected&#xD;
      individuals.The objectives of the study are to evaluate the safety, tolerability and&#xD;
      pharmacokinetics of a single administration of 3BNC117-LS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS&#xD;
      administered intravenously in HIV-uninfected and HIV-1 infected participants.&#xD;
&#xD;
      This study consists of two parts. In part A, study participants will be enrolled in an open&#xD;
      label manner to receive a single intravenous infusion of 3BNC117-LS at one of three&#xD;
      increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg). Participants in Part B will also&#xD;
      receive a single administration of 3BNC117-LS, however, the product administered in Part B of&#xD;
      the study derives from a new manufacturing lot. The manufacturing lot used in Part A had&#xD;
      incomplete glycosylation of the 3BNC117-LS light chain, which has been corrected in the new&#xD;
      lot. Participants in Part B will receive 3BNC117-LS intravenously at 30 mg/kg in an open&#xD;
      label manner (HIV-uninfected and HIV-infected) or will be randomized to receive a&#xD;
      subcutaneous injection of 3BNC117-LS or placebo in a double-blinded fashion (HIV-uninfected&#xD;
      only).&#xD;
&#xD;
      Part A has already been enrolled with 21 participants. Part B has a planned enrollment of 22&#xD;
      participants.&#xD;
&#xD;
      Part A&#xD;
&#xD;
        -  Group 1A (n=3-6) - HIV-uninfected individuals will be administered one infusion of&#xD;
           3BNC117-LS dosed at 3 mg/kg.&#xD;
&#xD;
        -  Group 1B (n=3-6) - HIV-uninfected individuals will be administered one infusion of&#xD;
           3BNC117-LS dosed at 10 mg/kg.&#xD;
&#xD;
        -  Group 1C (n=3-6) - HIV-uninfected individuals will be administered one infusion of&#xD;
           3BNC117-LS dosed at 30 mg/kg.&#xD;
&#xD;
        -  Group 2B (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels &lt; 20&#xD;
           copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels &lt; 100,000&#xD;
           copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.&#xD;
&#xD;
        -  Group 2C (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels &lt; 20&#xD;
           copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels &lt; 100,000&#xD;
           copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.&#xD;
&#xD;
      Part B&#xD;
&#xD;
        -  Group 1D (n=3) - HIV-uninfected individuals will be administered one infusion of&#xD;
           3BNC117-LS dosed at 30 mg/kg.&#xD;
&#xD;
        -  Group 2D (n=3) - HIV-infected individuals on ART with HIV-1 plasma RNA levels &lt; 20&#xD;
           copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.&#xD;
&#xD;
        -  Group 1E (n=8) - HIV-uninfected individuals will be administered a single 1 mL&#xD;
           (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.&#xD;
&#xD;
        -  Group 1F (n=8) - HIV-uninfected individuals will be administered a single 2 mL&#xD;
           (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.&#xD;
&#xD;
      Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks&#xD;
      1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up.&#xD;
&#xD;
      Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS&#xD;
      infusion, at the end of the infusion, and at multiple time points during study follow up.&#xD;
&#xD;
      Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS&#xD;
      infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C.&#xD;
&#xD;
      All participants will be followed for 48 weeks after 3BNC117-LS administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The number of participants who experience adverse events within 2 weeks after 3BNC117-LS infusion in all study groups</measure>
    <time_frame>2 weeks following the 3BNC117-LS infusion</time_frame>
    <description>Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination half-life (t1/2) of 3BNC117-LS in all study groups</measure>
    <time_frame>48 weeks</time_frame>
    <description>Elimination half-life (t1/2) of 3BNC117-LS in all study groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clearance (CL/F) of 3BNC117-LS in all study groups</measure>
    <time_frame>48 weeks</time_frame>
    <description>Clearance (CL/F) of 3BNC117-LS in all study groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of distribution (Vz/F) of 3BNC117-LS in all study groups</measure>
    <time_frame>48 weeks</time_frame>
    <description>Volume of distribution (Vz/F) of 3BNC117-LS in all study groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the curve of 3BNC117-LS in all study groups</measure>
    <time_frame>48 weeks</time_frame>
    <description>Area under the curve of 3BNC117-LS in all study groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decay curve of 3BNC117-LS in all study groups</measure>
    <time_frame>48 weeks</time_frame>
    <description>Decay curve of 3BNC117-LS in all study groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of induced anti-3BNC117-LS antibodies in all study groups.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Frequency of induced anti-3BNC117-LS antibodies in all study groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of induced anti-3BNC117-LS antibodies in all study groups.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Levels of induced anti-3BNC117-LS antibodies in all study groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of participants who experience adverse events during study follow-up</measure>
    <time_frame>48 weeks</time_frame>
    <description>Adverse events include signs, symptoms and laboratory abnormalities</description>
  </secondary_outcome>
  <other_outcome>
    <measure>3BNC117-LS levels in cervicovaginal and rectal fluids</measure>
    <time_frame>Day 0 and 2 weeks following 3BNC117-LS infusion</time_frame>
    <description>3BNC117-LS levels in cervicovaginal and rectal fluids</description>
  </other_outcome>
  <other_outcome>
    <measure>The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals</measure>
    <time_frame>48 weeks</time_frame>
    <description>The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals</description>
  </other_outcome>
  <other_outcome>
    <measure>Analysis of escape viruses in individuals not on ART</measure>
    <time_frame>48 weeks</time_frame>
    <description>Phenotypic and genotypic analysis of escape viruses in individuals not on ART.</description>
  </other_outcome>
  <other_outcome>
    <measure>Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.</description>
  </other_outcome>
  <other_outcome>
    <measure>HIV-specific T and B cell immune responses following 3BNC117-LS infusion</measure>
    <time_frame>48 weeks</time_frame>
    <description>HIV-specific T and B cell immune responses following 3BNC117-LS infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>T cell counts after 3BNC117-LS infusion</measure>
    <time_frame>48 weeks</time_frame>
    <description>Absolute and relative CD4 + and CD8+ T cell counts after 3BNC117-LS infusion.</description>
  </other_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Human Immunodeficiency Virus</condition>
  <arm_group>
    <arm_group_label>Group 1A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-infected individuals on ART with HIV-1 plasma RNA levels &lt; 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels &lt; 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-infected individuals on ART with HIV-1 plasma RNA levels &lt; 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels &lt; 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-infected individuals on ART with HIV-1 plasma RNA levels &lt; 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1F</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>3BNC117-LS</intervention_name>
    <description>Intravenous infusion of 3BNC117-LS</description>
    <arm_group_label>Group 1A</arm_group_label>
    <arm_group_label>Group 1B</arm_group_label>
    <arm_group_label>Group 1C</arm_group_label>
    <arm_group_label>Group 1D</arm_group_label>
    <arm_group_label>Group 1E</arm_group_label>
    <arm_group_label>Group 1F</arm_group_label>
    <arm_group_label>Group 2B</arm_group_label>
    <arm_group_label>Group 2C</arm_group_label>
    <arm_group_label>Group 2D</arm_group_label>
    <other_name>Monoclonal Antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Group 1E</arm_group_label>
    <arm_group_label>Group 1F</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Groups 1A-1F (HIV-uninfected):&#xD;
&#xD;
          1. Males and females, age 18 to 65&#xD;
&#xD;
          2. Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent&#xD;
             with low risk of HIV exposure.&#xD;
&#xD;
          3. If sexually active male or female, and participating in sexual activity that could&#xD;
             lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom&#xD;
             with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based&#xD;
             contraceptive with condom) from 10 days prior to and until seven months after&#xD;
             3BNC117-LS infusion, and agrees to safer sex counseling at each visit.&#xD;
&#xD;
               -  Female study participants of reproductive potential are defined as pre-menopausal&#xD;
                  women who have not had a sterilization procedure (e.g. hysterectomy, bilateral&#xD;
                  oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal&#xD;
                  if they have not had a menses for at least 12 months and have a FSH of greater&#xD;
                  than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24&#xD;
                  consecutive months.&#xD;
&#xD;
        Groups 2B-2D (HIV-infected):&#xD;
&#xD;
          1. Males and females, age 18 to 65.&#xD;
&#xD;
          2. HIV-1 infection confirmed by two laboratory assays.&#xD;
&#xD;
          3. HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels &lt;&#xD;
             100,000 copies/ml by standard assays (ART-naïve or off ART due to intolerance or by&#xD;
             choice), or on ART with HIV-1 plasma RNA levels &lt; 20 copies/ml. HIV-1 RNA levels&#xD;
             should be measured on 2 occasions, at least 1 week apart. At least one measurement&#xD;
             must be performed within 49 days prior to enrollment (day 0). Group 2D will only&#xD;
             enroll HIV-infected individuals on ART.&#xD;
&#xD;
          4. Current CD4+ T cell count &gt; 300 cells/μl.&#xD;
&#xD;
          5. If sexually active male or female, and participating in sexual activity that could&#xD;
             lead to pregnancy or transmission of HIV, agrees to use two effective methods of&#xD;
             contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting&#xD;
             IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven&#xD;
             months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Groups 1A-1F (HIV-uninfected):&#xD;
&#xD;
          1. Confirmed HIV-1 or HIV-2 infection.&#xD;
&#xD;
          2. History of immunodeficiency or autoimmune disease; use of systemic corticosteroids,&#xD;
             immunosuppressive anti-cancer, or other medications considered significant by the&#xD;
             trial physician within the last 6 months.&#xD;
&#xD;
          3. Any clinically significant acute or chronic medical condition (such as autoimmune&#xD;
             diseases) that in the opinion of the investigator would preclude participation.&#xD;
&#xD;
          4. Within the 12 months prior to enrollment, the participant has a history of sexually&#xD;
             transmitted infection.&#xD;
&#xD;
          5. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen&#xD;
             (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.&#xD;
&#xD;
          6. Laboratory abnormalities in the parameters listed:&#xD;
&#xD;
               -  Absolute neutrophil count ≤ 1,500 cells/µL;&#xD;
&#xD;
               -  Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;&#xD;
&#xD;
               -  Platelet count ≤ 125,000 cells/µL;&#xD;
&#xD;
               -  Alanine transaminase (ALT) ≥ 1.25 x ULN;&#xD;
&#xD;
               -  Aspartate transaminase (AST) ≥ 1.25 x ULN;&#xD;
&#xD;
               -  Alkaline phosphatase ≥ 1.5 x ULN;&#xD;
&#xD;
               -  Total bilirubin &gt; 1 x ULN;&#xD;
&#xD;
               -  Estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73m2.&#xD;
&#xD;
          7. Pregnancy or lactation.&#xD;
&#xD;
          8. Any vaccination within 14 days prior to 3BNC117-LS infusion.&#xD;
&#xD;
          9. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in&#xD;
             the past.&#xD;
&#xD;
         10. History of severe reaction to a vaccine or drug infusion or history of severe allergic&#xD;
             reactions.&#xD;
&#xD;
         11. Individuals with known hypersensitivity to any constituent of the investigational&#xD;
             product.&#xD;
&#xD;
         12. Receipt of another investigational product currently or within the past 12 weeks, or&#xD;
             expected concurrent participation in another study in which investigational products&#xD;
             will be administered.&#xD;
&#xD;
        Groups 2B-2D (HIV-infected):&#xD;
&#xD;
          1. Have a history of AIDS-defining illness within 3 years prior to enrollment.&#xD;
&#xD;
          2. History of systemic corticosteroids, immunosuppressive anti-cancer, or other&#xD;
             medications considered significant by the trial physician within the last 6 months.&#xD;
&#xD;
          3. Any clinically significant acute or chronic medical condition (such as autoimmune&#xD;
             diseases), other than HIV infection, that in the opinion of the investigator would&#xD;
             preclude participation.&#xD;
&#xD;
          4. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen&#xD;
             (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.&#xD;
&#xD;
          5. Laboratory abnormalities in the parameters listed below:&#xD;
&#xD;
               -  Absolute neutrophil count ≤ 1,000 cells/μl;&#xD;
&#xD;
               -  Hemoglobin ≤ 10 gm/dL;&#xD;
&#xD;
               -  Platelet count ≤ 100,000 cells/μl;&#xD;
&#xD;
               -  ALT ≥ 1.5 x ULN;&#xD;
&#xD;
               -  AST ≥ 1.5 x ULN;&#xD;
&#xD;
               -  Alkaline phosphatase ≥ 1.5 x ULN;&#xD;
&#xD;
               -  Total bilirubin &gt; 1 x ULN;&#xD;
&#xD;
               -  eGFR &lt; 60 mL/min/1.73m2.&#xD;
&#xD;
          6. Pregnancy or lactation.&#xD;
&#xD;
          7. Any vaccination within 14 days prior to 3BNC117-LS infusion.&#xD;
&#xD;
          8. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in&#xD;
             the past.&#xD;
&#xD;
          9. History of severe reaction to a vaccine or drug infusion or history of severe allergic&#xD;
             reactions.&#xD;
&#xD;
         10. Individuals with known hypersensitivity to any constituent of the investigational&#xD;
             product.&#xD;
&#xD;
         11. Receipt of another investigational product currently or within the past 12 weeks, or&#xD;
             expected concurrent participation in another study in which investigational products&#xD;
             will be administered.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marina Caskey, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Rockefeller University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Rockefeller University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Broadly Neutralizing Antibody</keyword>
  <keyword>3BNC117-LS</keyword>
  <keyword>First in Human</keyword>
  <keyword>Dose Escalation</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>
  </condition_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/NCT03254277
org study id: YCO-0946
nct id: NCT03254277
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The proposed study is a phase 1 study of the mAb 3BNC117-LS administered intravenously in HIV
      uninfected individuals and HIV-infected individuals, and subcutaneously in HIV-uninfected
      individuals.The objectives of the study are to evaluate the safety, tolerability and
      pharmacokinetics of a single administration of 3BNC117-LS.
The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS
      administered intravenously in HIV-uninfected and HIV-1 infected participants.

      This study consists of two parts. In part A, study participants will be enrolled in an open
      label manner to receive a single intravenous infusion of 3BNC117-LS at one of three
      increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg). Participants in Part B will also
      receive a single administration of 3BNC117-LS, however, the product administered in Part B of
      the study derives from a new manufacturing lot. The manufacturing lot used in Part A had
      incomplete glycosylation of the 3BNC117-LS light chain, which has been corrected in the new
      lot. Participants in Part B will receive 3BNC117-LS intravenously at 30 mg/kg in an open
      label manner (HIV-uninfected and HIV-infected) or will be randomized to receive a
      subcutaneous injection of 3BNC117-LS or placebo in a double-blinded fashion (HIV-uninfected
      only).

      Part A has already been enrolled with 21 participants. Part B has a planned enrollment of 22
      participants.

      Part A

        -  Group 1A (n=3-6) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 3 mg/kg.

        -  Group 1B (n=3-6) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 10 mg/kg.

        -  Group 1C (n=3-6) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 30 mg/kg.

        -  Group 2B (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20
           copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000
           copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.

        -  Group 2C (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20
           copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000
           copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

      Part B

        -  Group 1D (n=3) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 30 mg/kg.

        -  Group 2D (n=3) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20
           copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

        -  Group 1E (n=8) - HIV-uninfected individuals will be administered a single 1 mL
           (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

        -  Group 1F (n=8) - HIV-uninfected individuals will be administered a single 2 mL
           (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

      Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks
      1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up.

      Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS
      infusion, at the end of the infusion, and at multiple time points during study follow up.

      Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS
      infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C.

      All participants will be followed for 48 weeks after 3BNC117-LS administration.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The number of participants who experience adverse events within 2 weeks after 3BNC117-LS infusion in all study groups
time frame: 2 weeks following the 3BNC117-LS infusion
description: Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
measure: Elimination half-life (t1/2) of 3BNC117-LS in all study groups
time frame: 48 weeks
description: Elimination half-life (t1/2) of 3BNC117-LS in all study groups
measure: Clearance (CL/F) of 3BNC117-LS in all study groups
time frame: 48 weeks
description: Clearance (CL/F) of 3BNC117-LS in all study groups
measure: Volume of distribution (Vz/F) of 3BNC117-LS in all study groups
time frame: 48 weeks
description: Volume of distribution (Vz/F) of 3BNC117-LS in all study groups
measure: Area under the curve of 3BNC117-LS in all study groups
time frame: 48 weeks
description: Area under the curve of 3BNC117-LS in all study groups
measure: Decay curve of 3BNC117-LS in all study groups
time frame: 48 weeks
description: Decay curve of 3BNC117-LS in all study groups
measure: Frequency of induced anti-3BNC117-LS antibodies in all study groups.
time frame: 48 weeks
description: Frequency of induced anti-3BNC117-LS antibodies in all study groups.
measure: Levels of induced anti-3BNC117-LS antibodies in all study groups.
time frame: 48 weeks
description: Levels of induced anti-3BNC117-LS antibodies in all study groups.
measure: The number of participants who experience adverse events during study follow-up
time frame: 48 weeks
description: Adverse events include signs, symptoms and laboratory abnormalities
measure: 3BNC117-LS levels in cervicovaginal and rectal fluids
time frame: Day 0 and 2 weeks following 3BNC117-LS infusion
description: 3BNC117-LS levels in cervicovaginal and rectal fluids
measure: The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals
time frame: 48 weeks
description: The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals
measure: Analysis of escape viruses in individuals not on ART
time frame: 48 weeks
description: Phenotypic and genotypic analysis of escape viruses in individuals not on ART.
measure: Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.
time frame: 48 weeks
description: Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.
measure: Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.
time frame: 48 weeks
description: Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.
measure: HIV-specific T and B cell immune responses following 3BNC117-LS infusion
time frame: 48 weeks
description: HIV-specific T and B cell immune responses following 3BNC117-LS infusion
measure: T cell counts after 3BNC117-LS infusion
time frame: 48 weeks
description: Absolute and relative CD4 + and CD8+ T cell counts after 3BNC117-LS infusion.
arm group label: Group 1A
arm group type: Experimental
description: HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.
arm group label: Group 1B
arm group type: Experimental
description: HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
arm group label: Group 1C
arm group type: Experimental
description: HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
arm group label: Group 2B
arm group type: Experimental
description: HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
arm group label: Group 2C
arm group type: Experimental
description: HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
arm group label: Group 1D
arm group type: Experimental
description: HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
arm group label: Group 2D
arm group type: Experimental
description: HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
arm group label: Group 1E
arm group type: Experimental
description: HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
arm group label: Group 1F
arm group type: Experimental
description: HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
intervention type: Drug
intervention name: 3BNC117-LS
description: Intravenous infusion of 3BNC117-LS
arm group label: Group 1A
arm group label: Group 1B
arm group label: Group 1C
arm group label: Group 1D
arm group label: Group 1E
arm group label: Group 1F
arm group label: Group 2B
arm group label: Group 2C
arm group label: Group 2D
other name: Monoclonal Antibody
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Group 1E
arm group label: Group 1F
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marina Caskey, MD
role: Principal Investigator
affiliation: The Rockefeller University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
sharing ipd: No