xml: <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/NCT05986903</url>
    </required_header>
    <id_info>
      <org_study_id>22-EO033</org_study_id>
      <nct_id>NCT05986903</nct_id>
    </id_info>
    <brief_title>Influence of HLA-DQA1*05 Genotype in Adults With Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring.</brief_title>
    <acronym>Proa-DQ</acronym>
    <official_title>Influence of HLA-DQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring. A Prospective Multicenter Study.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hospital del Río Hortega</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Francisco Javier Garcia Alonso</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Jesús Barrio</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Hospital del Río Hortega</source>
    <oversight_info>
      <has_dmc>No</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>
        HLA-DQA1*05 variant carriers are at risk of developing antibodies against infliximab and&#xD;
        adalimumab with reduced TNF antagonist persistence.&#xD;
  &#xD;
        The impact of proactive therapeutic drug monitoring (PTDM) on this association has been&#xD;
        barely assessed.&#xD;
  &#xD;
        Therefor, we propose a cohort study including adult patients with Crohn's disease and&#xD;
        ulcerative colitis treated with TNF antagonists under proactive therapeutic drug monitoring.&#xD;
  &#xD;
        Our hypothesis is that, proactive therapeutic drug monitoring could be an alternative to&#xD;
        combination treatment with immunomodulators to increase TNF-antagonists' persistence in&#xD;
        HLA-DQA1*05 carriers.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Population study: patients with inflammatory bowel disease and initiation of anti-TNF therapy&#xD;
  &#xD;
        Inclusion and exclusion criteria&#xD;
  &#xD;
        The inclusion criteria are:&#xD;
  &#xD;
          -  Patient diagnosed with inflammatory bowel disease based on clinical, endoscopic, and&#xD;
             pathological criteria according to ECCO criteria.&#xD;
  &#xD;
          -  Initiation of anti-TNf, including infliximab and adalimumab.&#xD;
  &#xD;
          -  Subjects naïve to biological treatment&#xD;
  &#xD;
          -  Age &gt;18 years.&#xD;
  &#xD;
        The exclusion criteria are:&#xD;
  &#xD;
          -  No determination of HLA DQA1*5 allele.&#xD;
  &#xD;
          -  No proactive drug monitoring&#xD;
  &#xD;
          -  Initiation of anti-TNF treatment as prevention of post-surgical recurrence in Crohn's&#xD;
             disease during the first 12 months after surgery or, after that time, with a colonoscopy&#xD;
             with a Rutgeerts 0-1&#xD;
  &#xD;
          -  Anti-TNF treatment with combined treatment with immunomodulator. Prior initiation of&#xD;
             immunomodulator or prior use and suspension would not be a contraindication&#xD;
  &#xD;
          -  Initiation of anti-TNF treatment for extraintestinal manifestation&#xD;
  &#xD;
          -  Initiation of anti-TNF treatment during pregnancy.&#xD;
  &#xD;
        Proactive drug monitoring was defined as standardized determination of drug levels during&#xD;
        induction and maintenance, with optimization independently of the patient's clinical status,&#xD;
        until reaching target levels.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 11, 2023</start_date>
    <completion_date type="Anticipated">January 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">February 1, 2024</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>Corticosteroid-free clinical remission and treatment maintenance at week 54</measure>
      <time_frame>Week 54</time_frame>
      <description>Corticosteroid-free clinical remission was defined as Harvey Bradshaw score &lt;5 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis with no item exceeding one point, without corticosteroid</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Corticosteroid-free clinical response and remission at week 12.</measure>
      <time_frame>week 12</time_frame>
      <description>Corticosteroid-free clinical response was defined as Harvey Bradshaw score &lt; 5 or a decrease ≥ 3 points from baseline in Crohn's disease. For ulcerative colitis, a decrease in the partial Mayo Index of at least 3 points or 30% accompanied by a decrease in rectal bleeding by one point, without corticosteroid</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportions of patients with ultrasound remission at week 12 and 24</measure>
      <time_frame>week 12 and 24</time_frame>
      <description>Ultrasound remission was defined as SUS-CD 0 for Crohn's disease or a bowel wall thickness &lt; 2.1 mm for ulcerative colitis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportions of patients with clinical-biochemical remission at week 54.</measure>
      <time_frame>week 54</time_frame>
      <description>Clinical-biochemical remission was defined as CRP ≤ 5 mg/L and fecal calprotectin &lt; 150 mg/kg</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportions of endoscopic remission at week 54 between both groups.</measure>
      <time_frame>week 54</time_frame>
      <description>For Crohn's disease endoscopic remission was defined as a SES-CD &lt;3 points or absence of ulcerations (e.g. SES-CD ulceration subscores ¼ 0) For ulcerative colitis, a Mayo endoscopic subscore of 0 points, or UCEIS ≤1 points</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportions of primary failure between both groups</measure>
      <time_frame>week 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To compare drug levels at week 6 (infliximab) and week 4 (adalimumab) in subjects with a standard induction</measure>
      <time_frame>week 4 or 6</time_frame>
      <description>Drug monitoring at week 6 for infliximab and week 4 for adalimumab.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects with anti-drug antibodies at the end of induction and week 54.</measure>
      <time_frame>week 54</time_frame>
      <description>Anti-infliximab and anti-adalimumab antibodies at week 4 for adalimumab, at week 6 for infliximab and at week 54 for both.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">280</enrollment>
    <condition>Drug Monitoring</condition>
    <condition>Inflammatory Bowel Diseases</condition>
    <arm_group>
      <arm_group_label>HLA-DQA1*05 variant carriers</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>HLA-DQA1*05 non-carriers</arm_group_label>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tumor necrosis factor (TNF)-alpha inhibitors</intervention_name>
      <description>Proactive drug monitoring was defined as the assessment of trough concentrations to optimize dosing during induction therapy and intermittently thereafter regardless of symptoms or inflammatory markers.&#xD;
  During induction, the following target concentrations are employed: 25-30 mcg/ml (week 2) and 20 mcg/ml (week 6) for Infliximab and &gt; 10 mcg/ml (week 2 and 4) for Adalimumab. Checks are performed systematically at week 2 and 6 (infliximab) and at week 4 (adalimumab).&#xD;
  During the maintenance, the targets are 5-10 mcg/ml for Infliximab and 8-12 mcg/ml for Adalimumab. In case of perianal disease, the targets are 7-20 mcg/ml.</description>
      <arm_group_label>HLA-DQA1*05 non-carriers</arm_group_label>
      <arm_group_label>HLA-DQA1*05 variant carriers</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with a diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative&#xD;
          colitis and indeterminate colitis), who require starting anti-TNF for the first time.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of inflammatory bowel disease according to ECCO criteria.&#xD;
  &#xD;
            -  Older than 18 years&#xD;
  &#xD;
            -  Subjects naïve to biological treatment&#xD;
  &#xD;
            -  Anti-TNF treatment initiation (infliximab or adalimumab) due to intestinal activity&#xD;
               and/or perianal disease.&#xD;
  &#xD;
            -  Avaibility to evaluate HLA DQA1*05 status&#xD;
  &#xD;
            -  Proactive therapeutic drug monitoring of anti-TNF levels&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Initiation of anti-TNF treatment as prevention of post-surgical recurrence in Crohn's&#xD;
               disease during the first 12 months after surgery or, afterwards, if endoscopic&#xD;
               recurrence with a Rutgeerts 0-1.&#xD;
  &#xD;
            -  Initiation of anti-TNF treatment under combo treatment with immunomodulator. Prior&#xD;
               initiation of immunomodulator or prior use and suspension would not be a&#xD;
               contraindication.&#xD;
  &#xD;
            -  Initiation of anti-TNF treatment due to extraintestinal activity.&#xD;
  &#xD;
            -  Initiation of anti-TNF treatment by a non-gastroenterologist specialist.&#xD;
  &#xD;
            -  Initiation of anti-TNF treatment during pregnancy.&#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_contact>
      <last_name>Esteban Fuentes-Valenzuela, MD</last_name>
      <phone>+34 983 42 04 00</phone>
      <email>estebanfuentes_2@hotmail.co</email>
    </overall_contact>
    <location>
      <facility>
        <name>Hospital Universitario Rio Hortega</name>
        <address>
          <city>Valladolid</city>
          <country>Spain</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Esteban Fuentes-Valenzuela</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Spain</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Hospital del Río Hortega</investigator_affiliation>
      <investigator_full_name>Esteban Fuentes-Valenzuela</investigator_full_name>
      <investigator_title>MD</investigator_title>
    </responsible_party>
    <keyword>proactive therapeutic drug monitoring</keyword>
    <keyword>HLA-DQA1*05 genotype</keyword>
    <keyword>Anti-TNF</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Intestinal Diseases</mesh_term>
      <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05986903
  org study id: 22-EO033
  nct id: NCT05986903
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  HLA-DQA1*05 variant carriers are at risk of developing antibodies against infliximab and
        adalimumab with reduced TNF antagonist persistence.
  
        The impact of proactive therapeutic drug monitoring (PTDM) on this association has been
        barely assessed.
  
        Therefor, we propose a cohort study including adult patients with Crohn's disease and
        ulcerative colitis treated with TNF antagonists under proactive therapeutic drug monitoring.
  
        Our hypothesis is that, proactive therapeutic drug monitoring could be an alternative to
        combination treatment with immunomodulators to increase TNF-antagonists' persistence in
        HLA-DQA1*05 carriers.
  Population study: patients with inflammatory bowel disease and initiation of anti-TNF therapy
  
        Inclusion and exclusion criteria
  
        The inclusion criteria are:
  
          -  Patient diagnosed with inflammatory bowel disease based on clinical, endoscopic, and
             pathological criteria according to ECCO criteria.
  
          -  Initiation of anti-TNf, including infliximab and adalimumab.
  
          -  Subjects naïve to biological treatment
  
          -  Age >18 years.
  
        The exclusion criteria are:
  
          -  No determination of HLA DQA1*5 allele.
  
          -  No proactive drug monitoring
  
          -  Initiation of anti-TNF treatment as prevention of post-surgical recurrence in Crohn's
             disease during the first 12 months after surgery or, after that time, with a colonoscopy
             with a Rutgeerts 0-1
  
          -  Anti-TNF treatment with combined treatment with immunomodulator. Prior initiation of
             immunomodulator or prior use and suspension would not be a contraindication
  
          -  Initiation of anti-TNF treatment for extraintestinal manifestation
  
          -  Initiation of anti-TNF treatment during pregnancy.
  
        Proactive drug monitoring was defined as standardized determination of drug levels during
        induction and maintenance, with optimization independently of the patient's clinical status,
        until reaching target levels.
  observational model: Cohort
  time perspective: Prospective
  measure: Corticosteroid-free clinical remission and treatment maintenance at week 54
  time frame: Week 54
  description: Corticosteroid-free clinical remission was defined as Harvey Bradshaw score <5 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis with no item exceeding one point, without corticosteroid
  measure: Corticosteroid-free clinical response and remission at week 12.
  time frame: week 12
  description: Corticosteroid-free clinical response was defined as Harvey Bradshaw score < 5 or a decrease ≥ 3 points from baseline in Crohn's disease. For ulcerative colitis, a decrease in the partial Mayo Index of at least 3 points or 30% accompanied by a decrease in rectal bleeding by one point, without corticosteroid
  measure: Proportions of patients with ultrasound remission at week 12 and 24
  time frame: week 12 and 24
  description: Ultrasound remission was defined as SUS-CD 0 for Crohn's disease or a bowel wall thickness < 2.1 mm for ulcerative colitis
  measure: Proportions of patients with clinical-biochemical remission at week 54.
  time frame: week 54
  description: Clinical-biochemical remission was defined as CRP ≤ 5 mg/L and fecal calprotectin < 150 mg/kg
  measure: Proportions of endoscopic remission at week 54 between both groups.
  time frame: week 54
  description: For Crohn's disease endoscopic remission was defined as a SES-CD <3 points or absence of ulcerations (e.g. SES-CD ulceration subscores ¼ 0) For ulcerative colitis, a Mayo endoscopic subscore of 0 points, or UCEIS ≤1 points
  measure: Proportions of primary failure between both groups
  time frame: week 12
  measure: To compare drug levels at week 6 (infliximab) and week 4 (adalimumab) in subjects with a standard induction
  time frame: week 4 or 6
  description: Drug monitoring at week 6 for infliximab and week 4 for adalimumab.
  measure: Proportion of subjects with anti-drug antibodies at the end of induction and week 54.
  time frame: week 54
  description: Anti-infliximab and anti-adalimumab antibodies at week 4 for adalimumab, at week 6 for infliximab and at week 54 for both.
  arm group label: HLA-DQA1*05 variant carriers
  arm group label: HLA-DQA1*05 non-carriers
  intervention type: Drug
  intervention name: Tumor necrosis factor (TNF)-alpha inhibitors
  description: Proactive drug monitoring was defined as the assessment of trough concentrations to optimize dosing during induction therapy and intermittently thereafter regardless of symptoms or inflammatory markers.
  During induction, the following target concentrations are employed: 25-30 mcg/ml (week 2) and 20 mcg/ml (week 6) for Infliximab and > 10 mcg/ml (week 2 and 4) for Adalimumab. Checks are performed systematically at week 2 and 6 (infliximab) and at week 4 (adalimumab).
  During the maintenance, the targets are 5-10 mcg/ml for Infliximab and 8-12 mcg/ml for Adalimumab. In case of perianal disease, the targets are 7-20 mcg/ml.
  arm group label: HLA-DQA1*05 non-carriers
  arm group label: HLA-DQA1*05 variant carriers
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Esteban Fuentes-Valenzuela, MD
  phone: +34 983 42 04 00
  email: estebanfuentes_2@hotmail.co
  facility: 
  status: Recruiting
  contact: 
  country: Spain
  responsible party type: Principal Investigator
  investigator affiliation: Hospital del Río Hortega
  investigator full name: Esteban Fuentes-Valenzuela
  investigator title: MD
  mesh term: Intestinal Diseases
  mesh term: Inflammatory Bowel Diseases