<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/NCT03282851</url>
  </required_header>
  <id_info>
    <org_study_id>MS200740-0001</org_study_id>
    <nct_id>NCT03282851</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics/Pharmacodynamics (PK/PD) Equivalence Study of MSB11456</brief_title>
  <official_title>Randomized, Double-Blind, Parallel-Group, Single-Dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability and Immunogenicity of MSB11456, US-licensed Actemra® and EU-approved RoActemra® in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fresenius Kabi SwissBioSim GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fresenius Kabi SwissBioSim GmbH</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to compare the PK/PD of a single injection of investigational Medicinal&#xD;
      Product (IMP) MSB11456, US licensed Actemra and EU approved RoActemra in healthy adult&#xD;
      subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 27, 2017</start_date>
  <completion_date type="Actual">October 1, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Serum Concentration (Cmax) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under Curve From Tme Zero to 72 Hours After Dosing (AUC 0-72) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Area Under Curve From Zero to Infinity (AUC0-∞) Obtained by Extrapolation (AUC extra%) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time To Reach Maximum Serum Concentration (tmax) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Last Observed Serum Concentration (tlast) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Rate Constant (λz) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t½) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Total Body Clearance of Drug from Serum Following Subcutaneous Administration (CL/F) of MSB11456, US-licensed Actemra, and EU-approved RoActemra</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Injection Site Reactions, Laboratory Variables, Vital Signs and Electrocardiogram (ECG) Measurements</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity as Assessed by Incidence of Antidrug Antibodies (ADAs), Neutralizing Antibodies (NABs)</measure>
    <time_frame>Up to Day 48</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">696</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>MSB11456</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>US-licensed Actemra</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>EU-approved RoActemra</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MSB11456</intervention_name>
    <description>Subjects will receive a single injection of MSB11456 on Day 1.</description>
    <arm_group_label>MSB11456</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>US-licensed Actemra</intervention_name>
    <description>Subjects will receive a single injection of US-licensed actemra on Day 1.</description>
    <arm_group_label>US-licensed Actemra</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EU-approved RoActemra</intervention_name>
    <description>Subjects will receive a single injection of EU-approved RoActemra on Day 1.</description>
    <arm_group_label>EU-approved RoActemra</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female subjects, 18 to 55 years of age, with a body mass index (BMI)&#xD;
             between 18 and 29.9 kilogram per meter square (kg/m^2).&#xD;
&#xD;
          -  Subjects who are on adequate contraception as defined in the protocol and are willing&#xD;
             and able to comply with the scheduled study visits, Investigational medicinal product&#xD;
             (IMP) administration, safety laboratory tests, and all other study procedures.&#xD;
&#xD;
          -  Other protocol defined inclusion criteria could apply.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with history and/or current presence of clinically significant atopic allergy&#xD;
             (for example, asthma including childhood asthma, urticaria, angio-edema, eczematous&#xD;
             dermatitis).&#xD;
&#xD;
          -  Subjects with hypersensitivity or allergic reactions, including known or suspected&#xD;
             clinically relevant drug hypersensitivity to any components of the IMP formulations,&#xD;
             comparable drugs, or to latex.&#xD;
&#xD;
          -  Subjects who have active or latent tuberculosis as indicated by a positive&#xD;
             QuantiFERON®-Tuberculosis (TB) Gold test or a history of tuberculosis, lifetime&#xD;
             history of invasive systemic fungal infections (for example, histoplasmosis) or other&#xD;
             opportunistic infections, including recurrent or chronic local fungal infections,&#xD;
             frequent (more than 3 per year requiring treatment) chronic or recurrent infections,&#xD;
             having previously been treated with tocilizumab or taken a recombinant monoclonal&#xD;
             antibody.&#xD;
&#xD;
          -  Subjects who have received a live vaccine within 12 weeks before enrolling in this&#xD;
             study or planning for any such vaccination during the study or within 4 months after&#xD;
             IMP administration.&#xD;
&#xD;
          -  Other protocol defined exclusion criteria could apply.&#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>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Fresenius Kabi SwissBioSim GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research site</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research site</name>
      <address>
        <city>Christchurch</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MSB11456</keyword>
  <keyword>Actemra®</keyword>
  <keyword>RoActemra®</keyword>
  <!-- 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/NCT03282851
org study id: MS200740-0001
nct id: NCT03282851
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study aims to compare the PK/PD of a single injection of investigational Medicinal
      Product (IMP) MSB11456, US licensed Actemra and EU approved RoActemra in healthy adult
      subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Maximum Observed Serum Concentration (Cmax) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Area Under Curve From Tme Zero to 72 Hours After Dosing (AUC 0-72) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Percentage of Area Under Curve From Zero to Infinity (AUC0-∞) Obtained by Extrapolation (AUC extra%) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Time To Reach Maximum Serum Concentration (tmax) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Time to Last Observed Serum Concentration (tlast) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Apparent Terminal Rate Constant (λz) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Apparent Terminal Half-life (t½) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Apparent Total Body Clearance of Drug from Serum Following Subcutaneous Administration (CL/F) of MSB11456, US-licensed Actemra, and EU-approved RoActemra
time frame: Up to Day 48
measure: Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Injection Site Reactions, Laboratory Variables, Vital Signs and Electrocardiogram (ECG) Measurements
time frame: Up to Day 48
measure: Immunogenicity as Assessed by Incidence of Antidrug Antibodies (ADAs), Neutralizing Antibodies (NABs)
time frame: Up to Day 48
arm group label: MSB11456
arm group type: Experimental
arm group label: US-licensed Actemra
arm group type: Active Comparator
arm group label: EU-approved RoActemra
arm group type: Active Comparator
intervention type: Drug
intervention name: MSB11456
description: Subjects will receive a single injection of MSB11456 on Day 1.
arm group label: MSB11456
intervention type: Drug
intervention name: US-licensed Actemra
description: Subjects will receive a single injection of US-licensed actemra on Day 1.
arm group label: US-licensed Actemra
intervention type: Drug
intervention name: EU-approved RoActemra
description: Subjects will receive a single injection of EU-approved RoActemra on Day 1.
arm group label: EU-approved RoActemra
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Responsible
role: Study Director
affiliation: Fresenius Kabi SwissBioSim GmbH
facility: 
facility: 
country: New Zealand
country: Germany
responsible party type: Sponsor