<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/NCT03308357</url>
  </required_header>
  <id_info>
    <org_study_id>MSD IIS-57047- GIBSON</org_study_id>
    <nct_id>NCT03308357</nct_id>
  </id_info>
  <brief_title>Comparison of the Performance of SB2-Infliximab With Originator Infliximab in the Measure of Serum Concentrations in Serum</brief_title>
  <official_title>Comparison of the Performance of SB2-Infliximab With Originator Infliximab in the Measure of Serum Concentrations in Serum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Alfred</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Alfred</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The measurement of serum concentrations of infliximab (IFX)has now become a routine part of&#xD;
      optimal use of that drug. Trough values are used in two situations: (a) reactively where&#xD;
      there is loss of response to infliximab - therapeutic concentrations are indicate likely&#xD;
      non-response to the drug, whereas low levels are associated with the chance of regaining&#xD;
      response by increasing dosage; or (b) proactively, where dose optimisation in the maintenance&#xD;
      phase is performed to ensure ongoing efficacy and/or cost-effective use (where high levels&#xD;
      lead to reduction in dosage without loss of efficacy).&#xD;
&#xD;
      With the introduction of biosimilar infliximab into clinical practice, it is important to&#xD;
      demonstrate that the biosimilar behaves similarly in the assay used as does originator&#xD;
      infliximab to which the assays were developed. While unlikely to be different due to&#xD;
      identical protein core, such confirmation is needed before such assays can be used in&#xD;
      clinical practice with confidence.&#xD;
&#xD;
      AIMS&#xD;
&#xD;
        1. To compare the concentrations of biosimilar IFX (MSD-IFX) with that of originator IFX&#xD;
           (orig-IFX) when added to serum form healthy subjects and those with IBD when measured by&#xD;
           commonly-used commercial assays.&#xD;
&#xD;
        2. To compare the effect of freeze-thawing and storage at 4 oC on concentrations of&#xD;
           MSD-IFX.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      EXPERIMENTAL PLAN Serum This will separated from peripheral blood taken from 2 healthy&#xD;
      subjects, 2 patients with ulcerative colitis (one with quiescent and the other with active&#xD;
      disease), and 2 patients with Crohn's disease (one with quiescent and the other with active&#xD;
      disease). It will be used wither fresh or freshly thawed from serum stored at -20 oC.&#xD;
&#xD;
      Infliximab&#xD;
&#xD;
      Two sources of infliximab will be used:&#xD;
&#xD;
        -  Orig-IFX from Janssen&#xD;
&#xD;
        -  MSD-IFX from Merck Sharp &amp; Dome.&#xD;
&#xD;
      Preparation of simulated serum samples Fresh or thawed serum will be spiked with IFX to&#xD;
      obtained serum at concentrations of 0, 1, 2, 4, 6, 8, 10, 12, 15 and 20 ug/ml. This range&#xD;
      covers that seen in routine practice. These preparations will be used fresh or stored in&#xD;
      aliquots at 4 oC or -20 oC.&#xD;
&#xD;
      Assays to be evaluated These commercially-available assay kits have been chosen on the basis&#xD;
      that they are commonly used. They will all be used according to manufacturer's&#xD;
      recommendations.&#xD;
&#xD;
        -  SHIKARI Q-INFLIXI from Matriks Biotech;&#xD;
&#xD;
        -  LISA TRACKER Premium from Theradiag;&#xD;
&#xD;
        -  Promonitor ELISA kit from Grifols;&#xD;
&#xD;
        -  Quantum Blue Infliximab trough level rapid test from Buhlmann. Testing protocol The two&#xD;
           IFX molecules will be tested on the same plates in duplicate at the concentrations&#xD;
           prepared (as above). One assay plate will be sufficient for sera from 2 individuals. One&#xD;
           assay only will be performed on any one day.&#xD;
&#xD;
      For the direct comparisons, 3 ELISA assay kits will be required to assess 6 pairs of&#xD;
      IFX-spiked sera. The rapid test will be performed in duplicate in a similar way.&#xD;
&#xD;
      In order to assess the effect of storing at -20 oC followed by freeze-thawing, and storage at&#xD;
      4 oC, sera from two subjects will be prepared at one concentration (7 ug/ml), will tested&#xD;
      fresh and then again 7 days later after storage at the two temperatures. This will l be&#xD;
      performed with one assay kit only (the one performing the best in the comparative studies if&#xD;
      differences in kits emerge).&#xD;
&#xD;
      Analysis The result of MSD-IFX will be compared to those of Orig-IFX by plotting the&#xD;
      respective curves of concentrations and visually comparing them for each assay. The percent&#xD;
      deviation for each concentration will be calculated. The results will also be compared across&#xD;
      assays for each IFX source and then the findings compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 2017</start_date>
  <completion_date type="Anticipated">March 2018</completion_date>
  <primary_completion_date type="Anticipated">March 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Drug levels of infliximab originator and biosimilar infliximab</measure>
    <time_frame>Over the study duration (6 months)</time_frame>
    <description>Infliximab drug levels will be measured on a range of commercially available drug assays</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">6</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <arm_group>
    <arm_group_label>All six subjects</arm_group_label>
    <description>2 patients with ulcerative colitis; one with active disease and one in remission. 2 patients with Crohn's disease; one with active disease and one in remission. 2 healthly controls. Single blood sample from each participant, serum collected, that serum will be spiked with known concentrations of the originator infliximab and the biosimilar infliximab and then run on a range of assays to measure infliximab drug concentrations</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Drug assays to measure infliximab</intervention_name>
    <description>See protocol</description>
    <arm_group_label>All six subjects</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients attending the inflammatory bowel disease outpatient clinics at Alfred Health.&#xD;
        Healthy controls will be doctors attending the clinic&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Crohn's disease and ulcerative colitis, deemed to be in remission or with active&#xD;
             disease according to validated clinical scoring indices&#xD;
&#xD;
          -  healthy controls&#xD;
&#xD;
          -  Adult patients able to give informed consent to participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  not meeting inclusion criteria&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Mark G Ward, MBBS FRACP MD</last_name>
    <phone>+61390762223</phone>
    <email>m.ward@alfred.org.au</email>
  </overall_contact>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 9, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>October 12, 2017</last_update_submitted>
  <last_update_submitted_qc>October 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Alfred</investigator_affiliation>
    <investigator_full_name>Mark Ward</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>drug monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infliximab</mesh_term>
  </intervention_browse>
  <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/NCT03308357
org study id: MSD IIS-57047- GIBSON
nct id: NCT03308357
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The measurement of serum concentrations of infliximab (IFX)has now become a routine part of
      optimal use of that drug. Trough values are used in two situations: (a) reactively where
      there is loss of response to infliximab - therapeutic concentrations are indicate likely
      non-response to the drug, whereas low levels are associated with the chance of regaining
      response by increasing dosage; or (b) proactively, where dose optimisation in the maintenance
      phase is performed to ensure ongoing efficacy and/or cost-effective use (where high levels
      lead to reduction in dosage without loss of efficacy).

      With the introduction of biosimilar infliximab into clinical practice, it is important to
      demonstrate that the biosimilar behaves similarly in the assay used as does originator
      infliximab to which the assays were developed. While unlikely to be different due to
      identical protein core, such confirmation is needed before such assays can be used in
      clinical practice with confidence.

      AIMS

        1. To compare the concentrations of biosimilar IFX (MSD-IFX) with that of originator IFX
           (orig-IFX) when added to serum form healthy subjects and those with IBD when measured by
           commonly-used commercial assays.

        2. To compare the effect of freeze-thawing and storage at 4 oC on concentrations of
           MSD-IFX.
EXPERIMENTAL PLAN Serum This will separated from peripheral blood taken from 2 healthy
      subjects, 2 patients with ulcerative colitis (one with quiescent and the other with active
      disease), and 2 patients with Crohn's disease (one with quiescent and the other with active
      disease). It will be used wither fresh or freshly thawed from serum stored at -20 oC.

      Infliximab

      Two sources of infliximab will be used:

        -  Orig-IFX from Janssen

        -  MSD-IFX from Merck Sharp & Dome.

      Preparation of simulated serum samples Fresh or thawed serum will be spiked with IFX to
      obtained serum at concentrations of 0, 1, 2, 4, 6, 8, 10, 12, 15 and 20 ug/ml. This range
      covers that seen in routine practice. These preparations will be used fresh or stored in
      aliquots at 4 oC or -20 oC.

      Assays to be evaluated These commercially-available assay kits have been chosen on the basis
      that they are commonly used. They will all be used according to manufacturer's
      recommendations.

        -  SHIKARI Q-INFLIXI from Matriks Biotech;

        -  LISA TRACKER Premium from Theradiag;

        -  Promonitor ELISA kit from Grifols;

        -  Quantum Blue Infliximab trough level rapid test from Buhlmann. Testing protocol The two
           IFX molecules will be tested on the same plates in duplicate at the concentrations
           prepared (as above). One assay plate will be sufficient for sera from 2 individuals. One
           assay only will be performed on any one day.

      For the direct comparisons, 3 ELISA assay kits will be required to assess 6 pairs of
      IFX-spiked sera. The rapid test will be performed in duplicate in a similar way.

      In order to assess the effect of storing at -20 oC followed by freeze-thawing, and storage at
      4 oC, sera from two subjects will be prepared at one concentration (7 ug/ml), will tested
      fresh and then again 7 days later after storage at the two temperatures. This will l be
      performed with one assay kit only (the one performing the best in the comparative studies if
      differences in kits emerge).

      Analysis The result of MSD-IFX will be compared to those of Orig-IFX by plotting the
      respective curves of concentrations and visually comparing them for each assay. The percent
      deviation for each concentration will be calculated. The results will also be compared across
      assays for each IFX source and then the findings compared.
observational model: Cohort
time perspective: Prospective
measure: Drug levels of infliximab originator and biosimilar infliximab
time frame: Over the study duration (6 months)
description: Infliximab drug levels will be measured on a range of commercially available drug assays
arm group label: All six subjects
description: 2 patients with ulcerative colitis; one with active disease and one in remission. 2 patients with Crohn's disease; one with active disease and one in remission. 2 healthly controls. Single blood sample from each participant, serum collected, that serum will be spiked with known concentrations of the originator infliximab and the biosimilar infliximab and then run on a range of assays to measure infliximab drug concentrations
intervention type: Diagnostic Test
intervention name: Drug assays to measure infliximab
description: See protocol
arm group label: All six subjects
Serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Mark G Ward, MBBS FRACP MD
phone: +61390762223
email: m.ward@alfred.org.au
responsible party type: Principal Investigator
investigator affiliation: The Alfred
investigator full name: Mark Ward
investigator title: Dr
mesh term: Inflammatory Bowel Diseases
mesh term: Infliximab
sharing ipd: No