<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/NCT03014947</url>
  </required_header>
  <id_info>
    <org_study_id>EMR200588-001</org_study_id>
    <secondary_id>2014-000662-21</secondary_id>
    <nct_id>NCT03014947</nct_id>
  </id_info>
  <brief_title>MSB11022 in Healthy Subjects</brief_title>
  <official_title>A Phase I, Randomized, Double-Blind, Parallel-Group, Single-Dose Trial to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of MSB11022, US-Reference Product, and EU-Reference Medicinal Product (Humira®) in Healthy 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>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I, randomized, double-blind, parallel-group trial to compare Investigation&#xD;
      Medicinal Product (IMP) MSB11022, US- Reference Product (RP), and EU- Reference Medicinal&#xD;
      Product (RMP) (Humira®) in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary: Area Under the Concentration-Time Curve From time Zero Extrapolated to Infinity (AUC [0-inf])</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Serum Concentration (Cmax)</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-last])</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Serum Concentration (Tmax)</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution During the Terminal Phase (Vz/F)</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (t1/2)</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Total Clearance (CL/F)</measure>
    <time_frame>Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Injection Site Reactions</measure>
    <time_frame>Baseline up to Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs) and AEs Leading to Death</measure>
    <time_frame>Baseline up to Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Anti-drug Antibodies (ADA) for MSB11022</measure>
    <time_frame>Day 1 up to Day 71</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">237</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>MSB11022</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>US-licensed Humira</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>EU-approved Humira</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MSB11022</intervention_name>
    <description>Subjects will receive single dose of 40 milligram (mg) MSB11022 as a subcutaneous injection in the lower abdomen on Day 1.</description>
    <arm_group_label>MSB11022</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>US-licensed Humira</intervention_name>
    <description>Subject will receive single dose of 40 mg US-licensed Humira as a subcutaneous injection in the lower abdomen on Day 1.</description>
    <arm_group_label>US-licensed Humira</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EU-approved Humira</intervention_name>
    <description>Subject will receive single dose of 40 mg EU-approved Humira as a subcutaneous injection in the lower abdomen on Day 1.</description>
    <arm_group_label>EU-approved Humira</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects and healthy female subjects of non-childbearing potential aged&#xD;
             18 to 55 years, inclusive.&#xD;
&#xD;
          -  Other protocol defined inclusion criteria could apply.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent or history infections such as opportunistic infections, including sepsis,&#xD;
             pneumonia, and fungal infection.&#xD;
&#xD;
          -  Individuals with history of tuberculosis or diagnosed with tuberculosis by interview,&#xD;
             chest X-ray examination, or interferon-gamma release assay.&#xD;
&#xD;
          -  Concurrent or history of demyelinating disease (multiple sclerosis, etc.).&#xD;
&#xD;
          -  Concurrent or history of congestive cardiac failure.&#xD;
&#xD;
          -  Concurrent or history of allergic symptoms such as asthma bronchial, drug-induced&#xD;
             rash, and urticaria, which, in the judgment of the investigator, may affect&#xD;
             participation in this clinical study.&#xD;
&#xD;
          -  Concurrent or history of cardiac, hepatic, renal, gastrointestinal, respiratory,&#xD;
             and/or hematological function disorders, which, in the judgment of the investigator or&#xD;
             any of the sub investigators, may affect participation in this clinical study.&#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>
  </overall_official>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <results_reference>
    <citation>Hyland E, Mant T, Vlachos P, Attkins N, Ullmann M, Roy S, Wagner V. Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira((R)) in healthy subjects. Br J Clin Pharmacol. 2016 Oct;82(4):983-93. doi: 10.1111/bcp.13039. Epub 2016 Jul 28.</citation>
    <PMID>27285856</PMID>
  </results_reference>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>June 28, 2019</last_update_submitted>
  <last_update_submitted_qc>June 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MSB11022</keyword>
  <keyword>Humira®</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</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/NCT03014947
org study id: EMR200588-001
secondary id: 2014-000662-21
nct id: NCT03014947
lead sponsor: 
has dmc: No
This is a phase I, randomized, double-blind, parallel-group trial to compare Investigation
      Medicinal Product (IMP) MSB11022, US- Reference Product (RP), and EU- Reference Medicinal
      Product (RMP) (Humira®) in healthy subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Primary: Area Under the Concentration-Time Curve From time Zero Extrapolated to Infinity (AUC [0-inf])
time frame: Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Maximum Observed Serum Concentration (Cmax)
time frame: Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-last])
time frame: Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Time to Reach Maximum Observed Serum Concentration (Tmax)
time frame: Pre-dose 0 hour, post-dose 4, 8 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
time frame: Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Terminal Half-Life (t1/2)
time frame: Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Apparent Total Clearance (CL/F)
time frame: Pre-dose 0 hour, post-dose 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, 672, 840, 1008, 1344, 1680 hours
measure: Number of Subjects With Injection Site Reactions
time frame: Baseline up to Day 71
measure: Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs) and AEs Leading to Death
time frame: Baseline up to Day 71
measure: Number of Subjects With Anti-drug Antibodies (ADA) for MSB11022
time frame: Day 1 up to Day 71
arm group label: MSB11022
arm group type: Experimental
arm group label: US-licensed Humira
arm group type: Active Comparator
arm group label: EU-approved Humira
arm group type: Active Comparator
intervention type: Drug
intervention name: MSB11022
description: Subjects will receive single dose of 40 milligram (mg) MSB11022 as a subcutaneous injection in the lower abdomen on Day 1.
arm group label: MSB11022
intervention type: Drug
intervention name: US-licensed Humira
description: Subject will receive single dose of 40 mg US-licensed Humira as a subcutaneous injection in the lower abdomen on Day 1.
arm group label: US-licensed Humira
intervention type: Drug
intervention name: EU-approved Humira
description: Subject will receive single dose of 40 mg EU-approved Humira as a subcutaneous injection in the lower abdomen on Day 1.
arm group label: EU-approved Humira
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Responsible
role: Study Director
country: Germany
citation: Hyland E, Mant T, Vlachos P, Attkins N, Ullmann M, Roy S, Wagner V. Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira((R)) in healthy subjects. Br J Clin Pharmacol. 2016 Oct;82(4):983-93. doi: 10.1111/bcp.13039. Epub 2016 Jul 28.
PMID: 27285856
responsible party type: Sponsor
mesh term: Adalimumab