<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/NCT03036865</url>
  </required_header>
  <id_info>
    <org_study_id>BOS161721-01</org_study_id>
    <secondary_id>PXL232187</secondary_id>
    <nct_id>NCT03036865</nct_id>
  </id_info>
  <brief_title>Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of BOS161721 in Healthy Subjects</brief_title>
  <official_title>A Double-blind, Phase 1, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of BOS161721 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boston Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study BOS161721-01 is a randomized, single center, double-blind, placebo-controlled trial&#xD;
      conducted to study the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single&#xD;
      ascending intravenous (IV) and subcutaneous (SC) doses of BOS161721 or placebo in healthy&#xD;
      adult male and female participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study BOS161721-01 will consist of 7 single ascending dose (SAD) cohorts, each with 8&#xD;
      participants (6 active:2 placebo), and an eighth SAD cohort with 5 participants (all active).&#xD;
      Participants will be randomized in a 3:1 ratio (BOS161721:placebo) and will either receive a&#xD;
      single dose of BOS161721 (1, 3, 10, 22, 30, 60, 120, or 240 milligrams [mg]) or placebo.&#xD;
      Participants in Cohort 1 will receive the lowest dose, administered IV (1 mg), followed by&#xD;
      Cohort 2, in which participants will receive the second lowest dose, administered SC (3 mg).&#xD;
      BOS161721 or placebo will also be administered SC in Cohorts 3, 4, 5, 7, and 8. Participants&#xD;
      in Cohort 6 will be administered an IV dose of 22 mg (5 active) in parallel to the 60 mg&#xD;
      SC-dosed fifth cohort. This dose has been selected to generate a similar exposure to that&#xD;
      following the 30 mg SC dose. The actual Cohort 6 IV dose may be adjusted upon available PK&#xD;
      data.&#xD;
&#xD;
      Participants will be in this study for up to 56 weeks, which includes a Screening Period of&#xD;
      up to 28 days, a single-dose treatment day (during the in-subject treatment period), and a&#xD;
      52-week post-treatment Follow-up Period, which is required due to the potential half-life of&#xD;
      BOS161721.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">April 27, 2018</completion_date>
  <primary_completion_date type="Actual">April 27, 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>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with any treatment-emergent serious adverse event (TESAE)</measure>
    <time_frame>up to 52 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with any treatment-emergent non-serious adverse event (TEAE)</measure>
    <time_frame>up to 52 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with TESAEs of the indicated severity</measure>
    <time_frame>up to 52 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with TEAEs of the indicated severity</measure>
    <time_frame>up to 52 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal, clinically significant electrocardiogram findings</measure>
    <time_frame>Days -1 and 4 (Residential Period); Days 15, 30, and 90 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal, clinically significant vital sign (blood pressure, heart rate, temperature) values</measure>
    <time_frame>Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal, clinically significant hematology parameter values</measure>
    <time_frame>Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal, clinically significant clinical chemistry parameter values</measure>
    <time_frame>Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean total immunoglobulin G (IgG) levels</measure>
    <time_frame>Screening; Days -1 and 4 (Residential Period); Days 15, 30, 60, 210 and 270 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean total immunoglobulin M (IgM) levels</measure>
    <time_frame>Screening; Days -1 and 4 (Residential Period); Days 15, 30, 60, 210 and 270 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean cluster of differentiation 4 (CD4+) cell count</measure>
    <time_frame>Screening; Days -1, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal, clinically significant physical examination findings</measure>
    <time_frame>Screening; Day -1 (Residential Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal, clinically significant targeted physical examination findings</measure>
    <time_frame>Day 7 (Residential Period); Days 15, 44, 90, 180, 270, and 360 (Follow-up Period)</time_frame>
    <description>Single-day dosing will occur on Day 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean maximum observed concentration (Cmax) of intravenous (IV) BOS161721</measure>
    <time_frame>Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Cmax of subcutaneous (SC) BOS161721</measure>
    <time_frame>Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean first time to maximum concentration (Tmax) of IV BOS161721</measure>
    <time_frame>Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Tmax of SC BOS161721</measure>
    <time_frame>Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean area under the concentration-time curve (AUC) of IV BOS161721</measure>
    <time_frame>Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean AUC of SC BOS161721</measure>
    <time_frame>Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean terminal elimination half-life (t½) of IV BOS161721</measure>
    <time_frame>Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean t½ of SC BOS161721</measure>
    <time_frame>Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean systematic clearance (CL) of IV BOS161721</measure>
    <time_frame>Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean CL of SC BOS161721</measure>
    <time_frame>Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean volume of distribution (Vd) of IV BOS161721</measure>
    <time_frame>Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Vd of SC BOS161721</measure>
    <time_frame>Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with anti-drug antibodies (ADA) to BOS161721</measure>
    <time_frame>up to Day 60</time_frame>
  </secondary_outcome>
  <number_of_arms>15</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Healthy Participants</condition>
  <arm_group>
    <arm_group_label>Cohort 1: 1 mg, IV BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single intravenous (IV) dose of BOS161721 1 milligram (mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching IV placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: 3 mg, SC BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single subcutaneous (SC) dose of BOS161721 3 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching SC placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: 10 mg, SC BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single SC dose of BOS161721 10 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching SC placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4: 30 mg, SC BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single SC dose of BOS161721 30 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching SC placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5: 60 mg, SC BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single SC dose of BOS161721 60 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching SC placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6: 22 mg, IV BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single IV dose of BOS161721 22 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 7: 120 mg, SC BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single SC dose of BOS161721 120 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 7: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching SC placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 8: 240 mg, SC BOS161721</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will receive a single SC dose of BOS161721 240 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 8: matching placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each participant will receive matching SC placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BOS161721</intervention_name>
    <description>Single dose administered IV or SC</description>
    <arm_group_label>Cohort 1: 1 mg, IV BOS161721</arm_group_label>
    <arm_group_label>Cohort 2: 3 mg, SC BOS161721</arm_group_label>
    <arm_group_label>Cohort 3: 10 mg, SC BOS161721</arm_group_label>
    <arm_group_label>Cohort 4: 30 mg, SC BOS161721</arm_group_label>
    <arm_group_label>Cohort 5: 60 mg, SC BOS161721</arm_group_label>
    <arm_group_label>Cohort 6: 22 mg, IV BOS161721</arm_group_label>
    <arm_group_label>Cohort 7: 120 mg, SC BOS161721</arm_group_label>
    <arm_group_label>Cohort 8: 240 mg, SC BOS161721</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single dose administered IV or SC</description>
    <arm_group_label>Cohort 1: matching placebo</arm_group_label>
    <arm_group_label>Cohort 2: matching placebo</arm_group_label>
    <arm_group_label>Cohort 3: matching placebo</arm_group_label>
    <arm_group_label>Cohort 4: matching placebo</arm_group_label>
    <arm_group_label>Cohort 5: matching placebo</arm_group_label>
    <arm_group_label>Cohort 7: matching placebo</arm_group_label>
    <arm_group_label>Cohort 8: matching placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant voluntarily agrees to participate in this study and signs an Institutional&#xD;
             Review Board (IRB)-approved informed consent prior to performing any of the Screening&#xD;
             procedures&#xD;
&#xD;
          -  Participants should be between 18 and 55 years (both inclusive) of age at the time of&#xD;
             Screening, with a body mass index (BMI) between 17.5 and 32 kilograms per meters&#xD;
             squared (kg/m^2) (both inclusive) at the time of Screening, have a weight &gt; 50 kg and&#xD;
             &lt; 120 kg at the time of Screening, and be in general good health at least 8 weeks&#xD;
             prior to the Screening visit. Good health is defined as individuals without known&#xD;
             disease(s) as determined by a responsible physician, based on medical evaluation,&#xD;
             including medical history, physical examination, laboratory tests, imaging, and&#xD;
             cardiac monitoring.&#xD;
&#xD;
          -  Women of non-childbearing potential status:&#xD;
&#xD;
               -  Hysterectomy;&#xD;
&#xD;
               -  Bilateral tubal ligation/tubal occlusion;&#xD;
&#xD;
               -  Bilateral salpingectomy;&#xD;
&#xD;
               -  Bilateral oophorectomy;&#xD;
&#xD;
               -  Postmenopausal - defined as 12 months of spontaneous amenorrhea (In questionable&#xD;
                  cases, a blood sample will be taken with simultaneous testing of&#xD;
                  follicle-stimulating hormone (FSH) and estradiol levels, which should be&#xD;
                  consistent with menopausal range.)&#xD;
&#xD;
          -  Women of childbearing potential will be allowed to participate and have to agree to&#xD;
             use at least 1 of the following contraception methods at all times throughout study&#xD;
             participation in addition to either a condom with spermicide or a diaphragm/cervical&#xD;
             cap with spermicide:&#xD;
&#xD;
               -  Non-hormonal intrauterine device (IUD; Paragard®/copper)&#xD;
&#xD;
               -  Hormonal IUD (Mirena®)&#xD;
&#xD;
               -  Nexplanon® or implantation - progesterone inserts under the skin&#xD;
&#xD;
          -  Males will either be sterile, agree to be abstinent from Day -1 through the last study&#xD;
             visit, or agree to use 2 highly effective methods of contraception such as:&#xD;
&#xD;
               -  A male condom with spermicide;&#xD;
&#xD;
               -  A sterile sexual partner;&#xD;
&#xD;
               -  Use by female sexual partner of an IUD with spermicide; a female condom with&#xD;
                  spermicide; contraceptive sponge with spermicide; an intravaginal system; a&#xD;
                  diaphragm with spermicide; a cervical cap with spermicide; or oral, implantable,&#xD;
                  transdermal, or injectable contraceptive(s).&#xD;
&#xD;
          -  Non-smokers or people who smoke up to 5 cigarettes per day but less than 10 packs per&#xD;
             year&#xD;
&#xD;
          -  Participants should be willing and able to comply with all study procedures. The&#xD;
             criterion for inclusion will be reviewed and verified at Screening and admission.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior clinical trial experience with monoclonal antibodies if there were clinically&#xD;
             relevant tolerability issues with previous administration or if a washout period of 60&#xD;
             days or 5 half-lives (whichever is longer) has not occurred prior to the planned first&#xD;
             day of dosing&#xD;
&#xD;
          -  History of any autoimmune disease (e.g., rheumatoid arthritis, Lupus)&#xD;
&#xD;
          -  History or current diagnosis of cancer, with the exception of non-melanoma skin cancer&#xD;
             or cervical cancer in situ treated with apparent success with curative therapy&#xD;
             (response duration &gt; 5 years)&#xD;
&#xD;
          -  Asthma, currently treated with or in the opinion of the Principal Investigator likely&#xD;
             to require additional systemic glucocorticosteroid therapy during the study, is&#xD;
             exclusionary.&#xD;
&#xD;
          -  History of any clinically important drug or vaccine allergy or anaphylaxis&#xD;
&#xD;
          -  A cluster of differentiation 4 (CD4+) lymphocyte count &lt; 500 cell/millimeters cubed&#xD;
             (mm^3) at Screening&#xD;
&#xD;
          -  Positive anti-keyhole limpet hemocyanin (KLH) antibodies at Screening&#xD;
&#xD;
          -  Previous immunization with KLH&#xD;
&#xD;
          -  Known allergy to shellfish, KLH vaccine, or hypersensitivity to proteins foreign to&#xD;
             the body&#xD;
&#xD;
          -  Levels of Immunoglobulin G (IgG) and Immunoglobulin M (IgM) outside of reference value&#xD;
             deemed clinically significant by the Principal Investigator at Screening&#xD;
&#xD;
          -  History or sensitivity to heparin or heparin-induced thrombocytopenia&#xD;
&#xD;
          -  Participants with cryptosporidium in the stool sample at Screening&#xD;
&#xD;
          -  Abnormal bilirubin or alanine aminotransferase (ALT) at Screening as judged by the&#xD;
             Principal Investigator to be clinically significant&#xD;
&#xD;
          -  Positive urine drug screen at Screening or Day -1&#xD;
&#xD;
          -  History of alcohol dependence as determined by a positive alcohol serum test at&#xD;
             Screening or Day -1 or participants who consume more than 14 (female participants) or&#xD;
             21 (male participants) units of alcohol a week (unit = 1 glass of wine [125&#xD;
             milliliters (mL)/4 ounces] = 1 measure [25 mL/1 ounce] of spirits = 284 mL [10 ounces]&#xD;
             of beer)&#xD;
&#xD;
          -  Participants who have a positive test, or have been treated, for Hepatitis A,&#xD;
             Hepatitis B, Hepatitis C virus, human immunodeficiency virus (HIV), cytomegalovirus&#xD;
             (CMV) or Epstein-Barr virus (EBV). Regarding Hepatitis B, any of the following would&#xD;
             exclude the participant from the study:&#xD;
&#xD;
               -  Participants with positive Hepatitis B Surface antigen (HBsAg);&#xD;
&#xD;
               -  Participants with Hepatitis B DNA levels &gt; 200 copies/mL (quantified by real-time&#xD;
                  polymerase chain reaction) in case the participant is positive for Hepatitis B&#xD;
                  surface antibody (HBsAb) but negative for HBsAg;&#xD;
&#xD;
               -  Positive for Hepatitis B core antibody (HBcAb)&#xD;
&#xD;
          -  Current clinical, radiographic, or laboratory evidence of active tuberculosis (TB)&#xD;
&#xD;
          -  A history of active TB within the last 3 years before Screening, even if treated&#xD;
&#xD;
          -  Therapy for latent TB that has not been completed as per local country guidelines&#xD;
&#xD;
          -  Positive interferon gamma release assay (IGRA) for TB unless proper treatment is&#xD;
             documented, as described above&#xD;
&#xD;
          -  Donation of blood (&gt; 500 mL) or blood products within 2 months (56 days) prior to Day&#xD;
             -1&#xD;
&#xD;
          -  Any medically relevant pre-existing condition that could jeopardize the safety of the&#xD;
             participant during the trial&#xD;
&#xD;
          -  Any participant, on the judgment of the Principal Investigator, who would be&#xD;
             considered unsuitable for the clinical trial&#xD;
&#xD;
          -  A shingles infection in the last 6 months prior to Screening&#xD;
&#xD;
          -  Live vaccination or use of steroids in the last 2 months prior to Screening&#xD;
&#xD;
          -  Use of prescription medications (except for oral contraceptive) and over-the-counter&#xD;
             treatments, including herbal supplements such as St. John's Wart (except&#xD;
             multivitamins), in the 2 weeks prior to Screening&#xD;
&#xD;
          -  Participants with poor dental health and/or severe foot fungal infections, as judged&#xD;
             by the Principal Investigator&#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>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>November 17, 2020</last_update_submitted>
  <last_update_submitted_qc>November 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy participants</keyword>
  <keyword>BOS161721</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Pharmacodynamics</keyword>
  <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/NCT03036865
org study id: BOS161721-01
secondary id: PXL232187
nct id: NCT03036865
lead sponsor: 
has dmc: Yes
Study BOS161721-01 is a randomized, single center, double-blind, placebo-controlled trial
      conducted to study the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single
      ascending intravenous (IV) and subcutaneous (SC) doses of BOS161721 or placebo in healthy
      adult male and female participants.
Study BOS161721-01 will consist of 7 single ascending dose (SAD) cohorts, each with 8
      participants (6 active:2 placebo), and an eighth SAD cohort with 5 participants (all active).
      Participants will be randomized in a 3:1 ratio (BOS161721:placebo) and will either receive a
      single dose of BOS161721 (1, 3, 10, 22, 30, 60, 120, or 240 milligrams [mg]) or placebo.
      Participants in Cohort 1 will receive the lowest dose, administered IV (1 mg), followed by
      Cohort 2, in which participants will receive the second lowest dose, administered SC (3 mg).
      BOS161721 or placebo will also be administered SC in Cohorts 3, 4, 5, 7, and 8. Participants
      in Cohort 6 will be administered an IV dose of 22 mg (5 active) in parallel to the 60 mg
      SC-dosed fifth cohort. This dose has been selected to generate a similar exposure to that
      following the 30 mg SC dose. The actual Cohort 6 IV dose may be adjusted upon available PK
      data.

      Participants will be in this study for up to 56 weeks, which includes a Screening Period of
      up to 28 days, a single-dose treatment day (during the in-subject treatment period), and a
      52-week post-treatment Follow-up Period, which is required due to the potential half-life of
      BOS161721.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Number of participants with any treatment-emergent serious adverse event (TESAE)
time frame: up to 52 weeks
measure: Number of participants with any treatment-emergent non-serious adverse event (TEAE)
time frame: up to 52 weeks
measure: Number of participants with TESAEs of the indicated severity
time frame: up to 52 weeks
measure: Number of participants with TEAEs of the indicated severity
time frame: up to 52 weeks
measure: Number of participants with abnormal, clinically significant electrocardiogram findings
time frame: Days -1 and 4 (Residential Period); Days 15, 30, and 90 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Number of participants with abnormal, clinically significant vital sign (blood pressure, heart rate, temperature) values
time frame: Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Number of participants with abnormal, clinically significant hematology parameter values
time frame: Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Number of participants with abnormal, clinically significant clinical chemistry parameter values
time frame: Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Mean total immunoglobulin G (IgG) levels
time frame: Screening; Days -1 and 4 (Residential Period); Days 15, 30, 60, 210 and 270 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Mean total immunoglobulin M (IgM) levels
time frame: Screening; Days -1 and 4 (Residential Period); Days 15, 30, 60, 210 and 270 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Mean cluster of differentiation 4 (CD4+) cell count
time frame: Screening; Days -1, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Number of participants with abnormal, clinically significant physical examination findings
time frame: Screening; Day -1 (Residential Period)
description: Single-day dosing will occur on Day 1.
measure: Number of participants with abnormal, clinically significant targeted physical examination findings
time frame: Day 7 (Residential Period); Days 15, 44, 90, 180, 270, and 360 (Follow-up Period)
description: Single-day dosing will occur on Day 1.
measure: Mean maximum observed concentration (Cmax) of intravenous (IV) BOS161721
time frame: Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.
measure: Mean Cmax of subcutaneous (SC) BOS161721
time frame: Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.
measure: Mean first time to maximum concentration (Tmax) of IV BOS161721
time frame: Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.
measure: Mean Tmax of SC BOS161721
time frame: Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.
measure: Mean area under the concentration-time curve (AUC) of IV BOS161721
time frame: Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.
measure: Mean AUC of SC BOS161721
time frame: Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.
measure: Mean terminal elimination half-life (t½) of IV BOS161721
time frame: Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.
measure: Mean t½ of SC BOS161721
time frame: Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.
measure: Mean systematic clearance (CL) of IV BOS161721
time frame: Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.
measure: Mean CL of SC BOS161721
time frame: Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.
measure: Mean volume of distribution (Vd) of IV BOS161721
time frame: Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.
measure: Mean Vd of SC BOS161721
time frame: Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.
measure: Number of participants with anti-drug antibodies (ADA) to BOS161721
time frame: up to Day 60
arm group label: Cohort 1: 1 mg, IV BOS161721
arm group type: Experimental
description: Each participant will receive a single intravenous (IV) dose of BOS161721 1 milligram (mg).
arm group label: Cohort 1: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching IV placebo.
arm group label: Cohort 2: 3 mg, SC BOS161721
arm group type: Experimental
description: Each participant will receive a single subcutaneous (SC) dose of BOS161721 3 mg.
arm group label: Cohort 2: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching SC placebo.
arm group label: Cohort 3: 10 mg, SC BOS161721
arm group type: Experimental
description: Each participant will receive a single SC dose of BOS161721 10 mg.
arm group label: Cohort 3: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching SC placebo.
arm group label: Cohort 4: 30 mg, SC BOS161721
arm group type: Experimental
description: Each participant will receive a single SC dose of BOS161721 30 mg.
arm group label: Cohort 4: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching SC placebo.
arm group label: Cohort 5: 60 mg, SC BOS161721
arm group type: Experimental
description: Each participant will receive a single SC dose of BOS161721 60 mg.
arm group label: Cohort 5: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching SC placebo.
arm group label: Cohort 6: 22 mg, IV BOS161721
arm group type: Experimental
description: Each participant will receive a single IV dose of BOS161721 22 mg.
arm group label: Cohort 7: 120 mg, SC BOS161721
arm group type: Experimental
description: Each participant will receive a single SC dose of BOS161721 120 mg.
arm group label: Cohort 7: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching SC placebo.
arm group label: Cohort 8: 240 mg, SC BOS161721
arm group type: Experimental
description: Each participant will receive a single SC dose of BOS161721 240 mg.
arm group label: Cohort 8: matching placebo
arm group type: Placebo Comparator
description: Each participant will receive matching SC placebo.
intervention type: Drug
intervention name: BOS161721
description: Single dose administered IV or SC
arm group label: Cohort 1: 1 mg, IV BOS161721
arm group label: Cohort 2: 3 mg, SC BOS161721
arm group label: Cohort 3: 10 mg, SC BOS161721
arm group label: Cohort 4: 30 mg, SC BOS161721
arm group label: Cohort 5: 60 mg, SC BOS161721
arm group label: Cohort 6: 22 mg, IV BOS161721
arm group label: Cohort 7: 120 mg, SC BOS161721
arm group label: Cohort 8: 240 mg, SC BOS161721
intervention type: Drug
intervention name: Placebo
description: Single dose administered IV or SC
arm group label: Cohort 1: matching placebo
arm group label: Cohort 2: matching placebo
arm group label: Cohort 3: matching placebo
arm group label: Cohort 4: matching placebo
arm group label: Cohort 5: matching placebo
arm group label: Cohort 7: matching placebo
arm group label: Cohort 8: matching placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No