<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/NCT02996019</url>
  </required_header>
  <id_info>
    <org_study_id>GX29504</org_study_id>
    <nct_id>NCT02996019</nct_id>
  </id_info>
  <brief_title>A Study to Compare Pharmacokinetics (PK) of Etrolizumab Administered Subcutaneously by a Prefilled Syringe With Needle Safety Device (PFS-NSD) or an Auto-injector (AI)</brief_title>
  <official_title>A Randomized, Open-Label, 2-Part, 2-Arm, Parallel-Group, Single-Dose, Multi-Center Study in Healthy Subjects to Investigate the Comparability of Pharmacokinetics of Etrolizumab Administered Subcutaneously by a Prefilled Syringe With Needle Safety Device or an Auto-Injector</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <brief_summary>
    <textblock>
      This is a randomized, 2-part, 2-arm, open-label, parallel-group, multi-center study to&#xD;
      compare the PK of etrolizumab administered subcutaneously by an AI (test device) or a PFS-NSD&#xD;
      (reference device) in healthy participants. The study will comprise a pilot cohort (Part 1)&#xD;
      to estimate the geometric mean ratio (GMR) and variability of the maximum observed&#xD;
      concentration (Cmax) and area under the concentration-time curve (AUC) to confirm or&#xD;
      determine the sample size for the pivotal cohort (Part 2). The pivotal cohort will&#xD;
      demonstrate exposure comparability of Cmax, AUC from Hour 0 to the last measurable&#xD;
      concentration (AUClast), and AUC from Hour 0 to extrapolated infinite time (AUC0-inf), values&#xD;
      for a single dose of etrolizumab administered subcutaneously either by the AI or the PFS-NSD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2016</start_date>
  <completion_date type="Actual">April 9, 2018</completion_date>
  <primary_completion_date type="Actual">April 9, 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>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Cmax of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: AUClast of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: AUC0-inf of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Ratio of AUClast to AUC0-inf (AUCR) of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Cmax of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: AUClast of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: AUC0-inf of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1: Time to Maximum Observed Concentration (tmax) of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: tmax of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: t1/2 of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: AUCR of Etrolizumab</measure>
    <time_frame>Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events</measure>
    <time_frame>Part 1 and 2: Baseline up to Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Etrolizumab</measure>
    <time_frame>Part 1 and 2: Baseline up to Day 71</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Part 1: Etrolizumab AI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of etrolizumab via subcutaneous (SC) injection using the AI on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Etrolizumab PFS-NSD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Etrolizumab AI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of etrolizumab via SC injection using the AI on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Etrolizumab PFS-NSD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etrolizumab</intervention_name>
    <description>Etrolizumab will be administered at a dose of 105 milligrams (mg).</description>
    <arm_group_label>Part 1: Etrolizumab AI</arm_group_label>
    <arm_group_label>Part 1: Etrolizumab PFS-NSD</arm_group_label>
    <arm_group_label>Part 2: Etrolizumab AI</arm_group_label>
    <arm_group_label>Part 2: Etrolizumab PFS-NSD</arm_group_label>
    <other_name>RO5490261</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Auto-Injector (AI)</intervention_name>
    <description>The pre-filled AI will be used to administer etrolizumab.</description>
    <arm_group_label>Part 1: Etrolizumab AI</arm_group_label>
    <arm_group_label>Part 2: Etrolizumab AI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Prefilled Syringe With Needle Safety Device (PFS-NSD)</intervention_name>
    <description>The PFS-NSD will be used to administer etrolizumab.</description>
    <arm_group_label>Part 1: Etrolizumab PFS-NSD</arm_group_label>
    <arm_group_label>Part 2: Etrolizumab PFS-NSD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Within the body weight range of 60 to 100 kilograms, inclusive (for the pivotal cohort&#xD;
             [Part 2] only)&#xD;
&#xD;
          -  Within body mass index (BMI) range 18.0 to 30.0 kilograms per square meter (kg/m^2),&#xD;
             inclusive&#xD;
&#xD;
          -  In good health, determined by no clinically significant findings from medical history,&#xD;
             physical examination, 12-lead electrocardiogram (ECG), and vital signs&#xD;
&#xD;
          -  Females will be non-pregnant, non-lactating, and either postmenopausal (at least 12&#xD;
             months of non-therapy-induced amenorrhea)/surgically sterile (e.g., tubal ligation,&#xD;
             hysterectomy) for at least 90 days prior to enrolment, or agree to remain&#xD;
             abstinent/use a highly effective method of contraception for at least 24 weeks after&#xD;
             study drug administration&#xD;
&#xD;
          -  Males will either be sterile or agree to remain abstinent/use a highly effective&#xD;
             method of contraception for at least 24 weeks after study drug administration. Male&#xD;
             participants will refrain from sperm donation from Check-in (Day -1) until 24 weeks&#xD;
             following study drug administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior treatment with etrolizumab or other anti-integrin agents (including&#xD;
             natalizumab, vedolizumab, and efalizumab)&#xD;
&#xD;
          -  Any prior treatment with anti-mucosal addressin cell adhesion molecule 1&#xD;
             (anti-MAdCAM-1) agents&#xD;
&#xD;
          -  Any prior treatment with rituximab&#xD;
&#xD;
          -  Received intravenous corticosteroids within 30 days prior to Screening&#xD;
&#xD;
          -  Use of agents that deplete B or T cells (e.g., alemtuzumab, rituximab, or visilizumab)&#xD;
             within 12 months prior to randomization&#xD;
&#xD;
          -  Any prior immunosuppressive agents (including cyclosporine, tacrolimus, sirolimus,&#xD;
             mycophenolate mofetil)&#xD;
&#xD;
          -  Chronic nonsteroidal anti-inflammatory drug (NSAID) use&#xD;
&#xD;
          -  Use of any prescription medications/products within 14 days prior to Check in (Day -1)&#xD;
&#xD;
          -  History of demyelinating disease&#xD;
&#xD;
          -  Neurological conditions or diseases&#xD;
&#xD;
          -  History of cancer&#xD;
&#xD;
          -  History of alcoholism or drug addiction within less than (&lt;) 1 year prior to Screening&#xD;
&#xD;
          -  History of active or latent tuberculosis (TB), regardless of treatment history&#xD;
&#xD;
          -  History of recurrent opportunistic infections and/or history of severe disseminated&#xD;
             viral infections&#xD;
&#xD;
          -  Positive for human immunodeficiency virus (HIV) antibody&#xD;
&#xD;
          -  Any current or recent signs or symptoms of infection&#xD;
&#xD;
          -  Pregnant or lactating&#xD;
&#xD;
          -  Hospitalized within 4 weeks prior to and during Screening&#xD;
&#xD;
          -  History of organ transplant&#xD;
&#xD;
          -  Presence of skin rash at Screening or history of other skin disorders&#xD;
&#xD;
          -  Tattoos, scars, chronic rashes, or sunburn in the area of the designated injection&#xD;
             site&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Research Unit - Daytona</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Covance Clinical Research Unit Inc.; Covance Gfi Research</name>
      <address>
        <city>Evansville</city>
        <state>Indiana</state>
        <zip>47710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Covance Research Unit - Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75247</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Covance Clinical Research Unit, Inc</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>November 30, 2018</last_update_submitted>
  <last_update_submitted_qc>November 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etrolizumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02996019
org study id: GX29504
nct id: NCT02996019
lead sponsor: 
This is a randomized, 2-part, 2-arm, open-label, parallel-group, multi-center study to
      compare the PK of etrolizumab administered subcutaneously by an AI (test device) or a PFS-NSD
      (reference device) in healthy participants. The study will comprise a pilot cohort (Part 1)
      to estimate the geometric mean ratio (GMR) and variability of the maximum observed
      concentration (Cmax) and area under the concentration-time curve (AUC) to confirm or
      determine the sample size for the pivotal cohort (Part 2). The pivotal cohort will
      demonstrate exposure comparability of Cmax, AUC from Hour 0 to the last measurable
      concentration (AUClast), and AUC from Hour 0 to extrapolated infinite time (AUC0-inf), values
      for a single dose of etrolizumab administered subcutaneously either by the AI or the PFS-NSD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Part 1: Cmax of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 1: AUClast of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 1: AUC0-inf of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 1: Ratio of AUClast to AUC0-inf (AUCR) of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 2: Cmax of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 2: AUClast of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 2: AUC0-inf of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 1: Time to Maximum Observed Concentration (tmax) of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 2: tmax of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 2: t1/2 of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Part 2: AUCR of Etrolizumab
time frame: Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
measure: Percentage of Participants With Adverse Events
time frame: Part 1 and 2: Baseline up to Day 71
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Etrolizumab
time frame: Part 1 and 2: Baseline up to Day 71
arm group label: Part 1: Etrolizumab AI
arm group type: Experimental
description: Participants will receive a single dose of etrolizumab via subcutaneous (SC) injection using the AI on Day 1.
arm group label: Part 1: Etrolizumab PFS-NSD
arm group type: Active Comparator
description: Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.
arm group label: Part 2: Etrolizumab AI
arm group type: Experimental
description: Participants will receive a single dose of etrolizumab via SC injection using the AI on Day 1.
arm group label: Part 2: Etrolizumab PFS-NSD
arm group type: Active Comparator
description: Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.
intervention type: Drug
intervention name: Etrolizumab
description: Etrolizumab will be administered at a dose of 105 milligrams (mg).
arm group label: Part 1: Etrolizumab AI
arm group label: Part 1: Etrolizumab PFS-NSD
arm group label: Part 2: Etrolizumab AI
arm group label: Part 2: Etrolizumab PFS-NSD
other name: RO5490261
intervention type: Device
intervention name: Auto-Injector (AI)
description: The pre-filled AI will be used to administer etrolizumab.
arm group label: Part 1: Etrolizumab AI
arm group label: Part 2: Etrolizumab AI
intervention type: Device
intervention name: Prefilled Syringe With Needle Safety Device (PFS-NSD)
description: The PFS-NSD will be used to administer etrolizumab.
arm group label: Part 1: Etrolizumab PFS-NSD
arm group label: Part 2: Etrolizumab PFS-NSD
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Etrolizumab