<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/NCT03795142</url>
  </required_header>
  <id_info>
    <org_study_id>BGB149-101</org_study_id>
    <nct_id>NCT03795142</nct_id>
  </id_info>
  <brief_title>A First-time-in-human Study of BGB149</brief_title>
  <official_title>A Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BGB149 Following Single Dose Administration in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BerGenBio ASA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BerGenBio ASA</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial is a Phase I, first-in-human. The study is designed to evaluate the&#xD;
      safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of&#xD;
      BGB149 after single IV doses in healthy male and female subjects. Multiple dose levels will&#xD;
      be explored.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2018</start_date>
  <completion_date type="Actual">October 31, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The clinical study will be performed in a double-blinded manner for all cohorts.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of treatment-emergent clinical adverse events (AE) following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>Number of healthy volunteers experiencing adverse events (AE) AE categorized by grading for severity according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of treatment-emergent laboratory abnormalities following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>Number of healthy volunteers experiencing clinically significant abnormalities of clinical laboratory tests (hematology, coagulation, clinical chemistry and urinalysis); categorized by grading for severity according to the CTCAE version 5.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 Cmax following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>Cmax: measured maximum BGB149 concentration, determined directly from the concentration-time profile.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 Tmax following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>Tmax: Time of maximum BGB149 concentration determined directly from the concentration-time profile.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 AUC(0-last), following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>up to 85 days</time_frame>
    <description>Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration calculated using the linear-log trapezoidal rule.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 AUC(0-infinity) following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUClast + Clast/Lambda[z]) calculated using the linear-log trapezoidal rule.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 terminal elimination rate constant λz, following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>λz: The terminal elimination rate constant determined by selection of at least three data points on the terminal phase of the concentration-time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 t½: Terminal elimination half-life, following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>t½: Terminal elimination half-life calculated as: ln2/λz</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameters: BGB149 total body clearance (CL) following single intravenous (IV) administration of BGB149 or matched placebo</measure>
    <time_frame>85 days</time_frame>
    <description>CL: Total body clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity indicators: anti-drug antibodies [ADA]</measure>
    <time_frame>85 days</time_frame>
    <description>Immunogenicity - Detection and titre of anti-drug antibodies [ADA], determined using a validated assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity indicators: neutralizing antibodies [NAb]</measure>
    <time_frame>85 days</time_frame>
    <description>Immunogenicity - Detection and titre of neutralizing antibodies [NAb], determined using a validated assay (titres and NAb analyses performed when ADA screening is positive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics: detection of soluble Axl protein in circulation</measure>
    <time_frame>85 days</time_frame>
    <description>PD - Concentration of soluble Axl measured in serum after dosing, determined using a validated assay.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>single intravenous dose; BGB149</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single intravenous dose of BGB 149 or matched placebo will be administered on day 1 ascending doses will be administered in cohorts of 6 (randomised 4:2, active: placebo) at a planned four dose levels (maximum of six dose levels to be investigated under initial approved protocol) A sentinel cohort of 2 volunteers will randomly receive (1:1) either experimental or matched placebo infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>single intravenous dose; placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A single intravenous dose of BGB 149 or matched placebo will be administered on day 1 ascending doses will be administered in cohorts of 6 (randomised 4:2, active: placebo) at a planned four dose levels (maximum of six dose levels to be investigated under initial approved protocol) A sentinel cohort of 2 volunteers will randomly receive (1:1) either experimental or matched placebo infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BGB149</intervention_name>
    <description>Single Ascending Dose</description>
    <arm_group_label>single intravenous dose; BGB149</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo</description>
    <arm_group_label>single intravenous dose; placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The subject voluntarily agrees to participate in this study and signs an Independent&#xD;
             Ethics Committee approved informed consent form prior to performing any of the&#xD;
             screening procedures.&#xD;
&#xD;
          -  Healthy male and female subjects, between 18 to 55 years of age, inclusive, at the&#xD;
             screening visit.&#xD;
&#xD;
          -  If male, Must agree to use appropriate double-barrier contraception and to refrain&#xD;
             from donating sperm from the time of dosing until 3 months after dosing.&#xD;
&#xD;
          -  If female, Must be of non-childbearing potential (surgically sterile [hysterectomy or&#xD;
             bilateral tubal ligation] or postmenopausal ≥ 1 year with follicle stimulating hormone&#xD;
             &gt; 40 IU/L).&#xD;
&#xD;
          -  Body mass index between 18.0 and 30.0 kg/m2, inclusive, at the screening visit with a&#xD;
             weight of at least 50kg.&#xD;
&#xD;
          -  Non-smoker, defined as a subject who has not smoked previously and/or who has&#xD;
             discontinued smoking or the use of nicotine/nicotine-containing products (including&#xD;
             snuff and similar products) at least 3 months before the screening visit.&#xD;
&#xD;
          -  Subjects are in good health, as determined by medical history, physical examination,&#xD;
             vital signs assessment, resting 12-lead ECG and clinical laboratory evaluations within&#xD;
             normal reference ranges or outside of normal reference ranges considered not&#xD;
             clinically relevant by the Principal Investigator or designee.&#xD;
&#xD;
          -  Subject must have suitable veins for cannulation and/or repeated venipuncture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects of childbearing potential, or breastfeeding, or have a positive serum&#xD;
             pregnancy test at the screening visit or a positive urine pregnancy test on admission.&#xD;
&#xD;
          -  A positive urine cotinine result (&gt;500ng/mL) at the screening visit or on admission.&#xD;
&#xD;
          -  Subjects who have ongoing or significant history of alcoholism or drug/chemical abuse&#xD;
             in the past 5years, as determined by the Principal Investigator or designee.&#xD;
&#xD;
          -  Subjects who have positive urine drugs of abuse screen at the screening visit or on&#xD;
             admission, or a positive urine alcohol test at the screening visit or on admission.&#xD;
&#xD;
          -  Subjects who are unwilling to avoid the use of alcohol within 48 hours before any&#xD;
             study visit and while confined to the study center.&#xD;
&#xD;
          -  Subjects who are unwilling to abstain from heavy physical training from 7 days before&#xD;
             first dosing until the final follow-up visit.&#xD;
&#xD;
          -  Subjects who have used the following: Any prescribed medication within 14 days prior&#xD;
             to planned time of dosing. Non-prescription or over-the-counter medication, herbal and&#xD;
             dietary supplements such as St John's Wort, vitamins and minerals that could affect&#xD;
             the outcome of the study within 1 week prior to planned time of dosing. Live&#xD;
             attenuated vaccines and systemic corticosteroids within 3 months prior to planned time&#xD;
             of dosing.&#xD;
&#xD;
          -  Subjects who have donated blood in the 3 months prior to the screening visit, plasma&#xD;
             in the 7 days prior to the screening visit or platelets in the 6 weeks prior to the&#xD;
             screening visit.&#xD;
&#xD;
          -  Subjects who have a history of significant drug allergy (e.g., anaphylaxis) or any&#xD;
             clinically significant allergic condition (excluding non-active hay fever), as&#xD;
             determined by the Principal Investigator or designee.&#xD;
&#xD;
          -  Subjects who have had a clinically significant illness, medical/surgical procedure, or&#xD;
             trauma within 4 weeks of dosing, as determined by the Principal Investigator or&#xD;
             designee.&#xD;
&#xD;
          -  Subjects with history of gastrointestinal bleeding or ulceration or perforation;&#xD;
             history of Crohn's disease or any other inflammatory disorder of the gastrointestinal&#xD;
             tract.&#xD;
&#xD;
          -  Subjects with history of bone marrow transplant, with or without graft versus host&#xD;
             disease.&#xD;
&#xD;
          -  Subjects who have pulse, blood pressure, respiratory rate or oral body temperature&#xD;
             values outside the normal ranges at the screening visit or on admission that is, in&#xD;
             the opinion of the Principal Investigator or designee, clinically relevant and&#xD;
             increases the risk of participating in the study.&#xD;
&#xD;
          -  Results of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline&#xD;
             phosphatase (ALP) and/or total bilirubin (TBL) above the upper limit of normal (ULN),&#xD;
             as confirmed by subsequent repeat assessment, at the screening visit and on admission.&#xD;
&#xD;
          -  A positive serology test for hepatitis A virus IgM antibodies (anti-HAV IgM),&#xD;
             hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or antibodies&#xD;
             to human immunodeficiency virus (HIV) Type 1 and/or Type 2 at the screening visit.&#xD;
&#xD;
          -  Subjects who are still participating in another clinical study or received last study&#xD;
             drug dose in a clinical study within 3 months or 5 half-lives, prior to dosing in this&#xD;
             study, whichever is longer.&#xD;
&#xD;
          -  Employees of the Sponsor or the contract research organization (CRO), with direct&#xD;
             involvement in the proposed study or other studies under the direction of the&#xD;
             Principal Investigator or the CRO, as well as close relatives of the employees.&#xD;
&#xD;
          -  Subjects who are unlikely to comply with the protocol requirements, instructions and&#xD;
             study related restrictions; e.g., uncooperative attitude, inability to return for&#xD;
             follow-up visits and improbability of completing the clinical study.&#xD;
&#xD;
          -  Vulnerable subjects defined as individuals whose willingness to volunteer in a&#xD;
             clinical study may be unduly influenced by the expectation, whether justified or not,&#xD;
             of benefits associated with participation, or of a retaliatory response from senior&#xD;
             members of a hierarchy in case of refusal to participate (e.g., persons in detention,&#xD;
             minors and those incapable of giving consent).&#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>Muna Albayaty, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parexel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parexel Northwick Park</name>
      <address>
        <city>London</city>
        <state>Harrow, Middlesex</state>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>November 23, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>March 1, 2022</last_update_submitted>
  <last_update_submitted_qc>March 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</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>


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/NCT03795142
org study id: BGB149-101
nct id: NCT03795142
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This clinical trial is a Phase I, first-in-human. The study is designed to evaluate the
      safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of
      BGB149 after single IV doses in healthy male and female subjects. Multiple dose levels will
      be explored.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Screening
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The clinical study will be performed in a double-blinded manner for all cohorts.
measure: Incidence of treatment-emergent clinical adverse events (AE) following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: Number of healthy volunteers experiencing adverse events (AE) AE categorized by grading for severity according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).
measure: Frequency of treatment-emergent laboratory abnormalities following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: Number of healthy volunteers experiencing clinically significant abnormalities of clinical laboratory tests (hematology, coagulation, clinical chemistry and urinalysis); categorized by grading for severity according to the CTCAE version 5.0.
measure: Pharmacokinetic Parameters: BGB149 Cmax following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: Cmax: measured maximum BGB149 concentration, determined directly from the concentration-time profile.
measure: Pharmacokinetic Parameters: BGB149 Tmax following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: Tmax: Time of maximum BGB149 concentration determined directly from the concentration-time profile.
measure: Pharmacokinetic Parameters: BGB149 AUC(0-last), following single intravenous (IV) administration of BGB149 or matched placebo
time frame: up to 85 days
description: Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration calculated using the linear-log trapezoidal rule.
measure: Pharmacokinetic Parameters: BGB149 AUC(0-infinity) following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUClast + Clast/Lambda[z]) calculated using the linear-log trapezoidal rule.
measure: Pharmacokinetic Parameters: BGB149 terminal elimination rate constant λz, following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: λz: The terminal elimination rate constant determined by selection of at least three data points on the terminal phase of the concentration-time curve.
measure: Pharmacokinetic Parameters: BGB149 t½: Terminal elimination half-life, following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: t½: Terminal elimination half-life calculated as: ln2/λz
measure: Pharmacokinetic Parameters: BGB149 total body clearance (CL) following single intravenous (IV) administration of BGB149 or matched placebo
time frame: 85 days
description: CL: Total body clearance
measure: Immunogenicity indicators: anti-drug antibodies [ADA]
time frame: 85 days
description: Immunogenicity - Detection and titre of anti-drug antibodies [ADA], determined using a validated assay.
measure: Immunogenicity indicators: neutralizing antibodies [NAb]
time frame: 85 days
description: Immunogenicity - Detection and titre of neutralizing antibodies [NAb], determined using a validated assay (titres and NAb analyses performed when ADA screening is positive
measure: Pharmacodynamics: detection of soluble Axl protein in circulation
time frame: 85 days
description: PD - Concentration of soluble Axl measured in serum after dosing, determined using a validated assay.
arm group label: single intravenous dose; BGB149
arm group type: Experimental
description: A single intravenous dose of BGB 149 or matched placebo will be administered on day 1 ascending doses will be administered in cohorts of 6 (randomised 4:2, active: placebo) at a planned four dose levels (maximum of six dose levels to be investigated under initial approved protocol) A sentinel cohort of 2 volunteers will randomly receive (1:1) either experimental or matched placebo infusion
arm group label: single intravenous dose; placebo
arm group type: Placebo Comparator
description: A single intravenous dose of BGB 149 or matched placebo will be administered on day 1 ascending doses will be administered in cohorts of 6 (randomised 4:2, active: placebo) at a planned four dose levels (maximum of six dose levels to be investigated under initial approved protocol) A sentinel cohort of 2 volunteers will randomly receive (1:1) either experimental or matched placebo infusion
intervention type: Biological
intervention name: BGB149
description: Single Ascending Dose
arm group label: single intravenous dose; BGB149
intervention type: Biological
intervention name: Placebo
description: Matching placebo
arm group label: single intravenous dose; placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Muna Albayaty, MD
role: Principal Investigator
affiliation: Parexel
facility: 
country: United Kingdom
responsible party type: Sponsor
sharing ipd: No