<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/NCT03765450</url>
  </required_header>
  <id_info>
    <org_study_id>RP1713</org_study_id>
    <nct_id>NCT03765450</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of IFX and TNF Concentrations in Serum, Stool, and Colonic Mucosa in Acute Severe Ulcerative Colitis</brief_title>
  <acronym>PROTOS</acronym>
  <official_title>Pharmacokinetics of Infliximab and Tumor Necrosis Factor Concentrations in Serum, Stool, and Colonic Mucosa in Acute Severe Ulcerative Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alimentiv Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alimentiv Inc.</source>
  <oversight_info>
    <has_dmc>No</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 is an open-label, prospective, observational study with the primary objective to&#xD;
      characterize the pharmacokinetics of infliximab in patients with Acute Severe Ulcerative&#xD;
      Colitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Acute Severe Ulcerative Colitis (ASUC), drug exposure may be affected by intestinal&#xD;
      protein loss leading to hypoalbuminemia and rapid clearance of infliximab (IFX). Importantly,&#xD;
      2 studies have associated the loss of IFX in stool with poor outcomes. Multiple observational&#xD;
      studies have identified that patients with faster IFX clearance have worse clinical outcomes&#xD;
      and higher rates of antidrug antibody formation. To better understand optimal dosing of IFX&#xD;
      in ASUC, the pharmacokinetics of IFX in association with outcomes must be better defined in&#xD;
      this setting.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 21, 2018</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Actual">November 7, 2022</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>Inter-compartmental Difference in Infliximab Concentration</measure>
    <time_frame>22 weeks</time_frame>
    <description>Infliximab population pharmacokinetics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Proteome</measure>
    <time_frame>22 weeks</time_frame>
    <description>Change in Proteomics before and after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Transcriptome</measure>
    <time_frame>22 weeks</time_frame>
    <description>Change in Transcriptomics before and after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Robarts Histopathologic Index</measure>
    <time_frame>22 weeks</time_frame>
    <description>Change in Robarts Histopathologic Index before and after therapy The RHI consists of 4 histological items (extent of chronic inflammatory cell infiltration, neutrophils in the lamina propria, neutrophils in the epithelium, and erosions and ulceration) scored from 0 to 3 and multiplied by a weighting factor. The total RHI score is calculated by summing the weighted scores of the histological items, with total scores ranging from 0 (no disease activity) to 33 (severe disease activity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mayo Clinic Endoscopic Score</measure>
    <time_frame>22 weeks</time_frame>
    <description>Change in Mayo Clinic Endoscopic Score before and after therapy The Mayo Clinic score (MCS) scores 4 variables (stool frequency, rectal bleeding, a physician's global assessment and endoscopic findings with flexible sigmoidoscopy). The endoscopic component of the MCS assesses disease activity on a 4-point scale (0-3 points), with higher scores representing more severe disease activity. Mucosal healing is often defined as an endoscopy score of 0 or 1.&#xD;
Normal or inactive disease = 0 Mild disease (erythema, decreased vascular pattern, mild friability) = 1 Moderate disease (marked erythema, absent vascular pattern, friability, erosions) = 2 Severe (spontaneous bleeding, ulceration) = 3</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">18</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Single Group Study</arm_group_label>
    <description>Patients with Acute Severe Ulcerative Colitis who are either a) biologic-naïve or b) biologic-experienced without a known history of anti-infliximab antibodies requiring infliximab infusion therapy as a part of standard of care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <description>Patients will receive infliximab at the discretion of their physician as part of standard of care.</description>
    <arm_group_label>Single Group Study</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, stool, tissue, blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed with acute severe ulcerative colitis, who are biologic-naive or&#xD;
        biologic-experienced without a known history of anti-infliximab antibodies and will be&#xD;
        receiving infliximab infusion therapy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Present to hospital with ASUC based on Truelove and Witts criteria,33 defined as the&#xD;
             presence of more than 6 bloody stools per day along with any 1 of the following:&#xD;
             tachycardia &gt; 90 beats per minute, fever &gt; 37.8 °C, hemoglobin &lt; 10.5 g/dL, and&#xD;
             erythrocyte sedimentation rate (ESR) &gt; 30 mm/h (or CRP &gt; 30 mg/L [high-sensitivity CRP&#xD;
             &gt; 300 mg/L]) is a suitable surrogate if ESR is not available1).&#xD;
&#xD;
          -  Have a partial MCS &gt; 7.&#xD;
&#xD;
          -  Have a Mayo Clinic ES ≥ 2 with disease extending 15 cm or more beyond the anal verge.&#xD;
&#xD;
          -  Require rescue inpatient IFX infusion as part of routine care. Note, the IFX treatment&#xD;
             regimen is not defined by this protocol and any dosage regimen is acceptable for the&#xD;
             purposes of this study, such as standard or accelerated induction regimens.&#xD;
&#xD;
          -  Be able to speak English and participate fully in all aspects of this clinical trial.&#xD;
&#xD;
          -  Provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A known history of being positive for anti-IFX antibodies.&#xD;
&#xD;
          -  Have a serious active infection, active malignancy, or any other known condition&#xD;
             contraindicated with infliximab therapy, according to current prescribing information.&#xD;
&#xD;
          -  Serious underlying disease other than ASUC, or other physical or psychosocial&#xD;
             condition that, in the opinion of the investigator, may interfere with the subject's&#xD;
             ability to participate fully in the study.&#xD;
&#xD;
          -  Prior enrollment in the current study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Niels Vande Casteele</last_name>
    <role>Study Director</role>
    <affiliation>UCSD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSD</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornell University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Center</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
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  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ASUC</keyword>
  <keyword>Infliximab</keyword>
  <keyword>Optimal Dose</keyword>
  <keyword>Optimal Frequency</keyword>
  <keyword>Theraputic Drug Monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infliximab</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/NCT03765450
org study id: RP1713
nct id: NCT03765450
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, prospective, observational study with the primary objective to
      characterize the pharmacokinetics of infliximab in patients with Acute Severe Ulcerative
      Colitis.
In Acute Severe Ulcerative Colitis (ASUC), drug exposure may be affected by intestinal
      protein loss leading to hypoalbuminemia and rapid clearance of infliximab (IFX). Importantly,
      2 studies have associated the loss of IFX in stool with poor outcomes. Multiple observational
      studies have identified that patients with faster IFX clearance have worse clinical outcomes
      and higher rates of antidrug antibody formation. To better understand optimal dosing of IFX
      in ASUC, the pharmacokinetics of IFX in association with outcomes must be better defined in
      this setting.
observational model: Cohort
time perspective: Prospective
measure: Inter-compartmental Difference in Infliximab Concentration
time frame: 22 weeks
description: Infliximab population pharmacokinetics
measure: Change in Proteome
time frame: 22 weeks
description: Change in Proteomics before and after therapy
measure: Change in Transcriptome
time frame: 22 weeks
description: Change in Transcriptomics before and after therapy
measure: Change in Robarts Histopathologic Index
time frame: 22 weeks
description: Change in Robarts Histopathologic Index before and after therapy The RHI consists of 4 histological items (extent of chronic inflammatory cell infiltration, neutrophils in the lamina propria, neutrophils in the epithelium, and erosions and ulceration) scored from 0 to 3 and multiplied by a weighting factor. The total RHI score is calculated by summing the weighted scores of the histological items, with total scores ranging from 0 (no disease activity) to 33 (severe disease activity).
measure: Change in Mayo Clinic Endoscopic Score
time frame: 22 weeks
description: Change in Mayo Clinic Endoscopic Score before and after therapy The Mayo Clinic score (MCS) scores 4 variables (stool frequency, rectal bleeding, a physician's global assessment and endoscopic findings with flexible sigmoidoscopy). The endoscopic component of the MCS assesses disease activity on a 4-point scale (0-3 points), with higher scores representing more severe disease activity. Mucosal healing is often defined as an endoscopy score of 0 or 1.
Normal or inactive disease = 0 Mild disease (erythema, decreased vascular pattern, mild friability) = 1 Moderate disease (marked erythema, absent vascular pattern, friability, erosions) = 2 Severe (spontaneous bleeding, ulceration) = 3
arm group label: Single Group Study
description: Patients with Acute Severe Ulcerative Colitis who are either a) biologic-naïve or b) biologic-experienced without a known history of anti-infliximab antibodies requiring infliximab infusion therapy as a part of standard of care.
intervention type: Drug
intervention name: Infliximab
description: Patients will receive infliximab at the discretion of their physician as part of standard of care.
arm group label: Single Group Study
Serum, stool, tissue, blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Niels Vande Casteele
role: Study Director
affiliation: UCSD
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
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responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Infliximab