<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/NCT03017014</url>
  </required_header>
  <id_info>
    <org_study_id>P15-759</org_study_id>
    <nct_id>NCT03017014</nct_id>
  </id_info>
  <brief_title>A Study to Assess Safety and Effectiveness of Adalimumab for Treating Children and Adolescents With Crohn's Disease in Real Life Conditions</brief_title>
  <acronym>LEA</acronym>
  <official_title>Assessing Long-term Safety and Effectiveness of Adalimumab for Treating Children and Adolescents With Crohn's Disease in Real Life Conditions-LEA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate long-term effectiveness of adalimumab in&#xD;
      pediatric participants starting a treatment for Crohn's disease in real life conditions,&#xD;
      namely to describe the time to loss of clinical benefit in a time to event approach. Main&#xD;
      secondary objectives are to describe growth and pubertal development and to describe&#xD;
      long-term safety. The participants will be followed-up up to 10 years.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Actual">October 14, 2019</completion_date>
  <primary_completion_date type="Actual">October 14, 2019</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>Time to loss of clinical benefit</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Loss of clinical benefit will be defined as one of the following:&#xD;
Loss of efficacy leading to adalimumab discontinuation or&#xD;
Introduction / reinforcement of other immunosuppressants (ratio dose/weight) or&#xD;
Introduction / reinforcement of corticosteroids (ratio dose/weight; reinforcement of corticosteroids are allowed within the 4 first months after start of adalimumab)&#xD;
Introduction of enteral nutrition&#xD;
CD-related surgery, discontinuation of adalimumab due to adverse event, death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with dose escalation (dose and/or frequency of injections)</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Dosing and/or frequency of injections is monitored to assess dose escalation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median percent change from baseline in C-reactive protein (CRP)</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>The median percent change from baseline in CRP is assessed at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median percent change from baseline in calprotectin</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>The median percent change from baseline in calprotectin us assessed at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in weighted Pediatric Crohn's Disease Activity Index (PCDAI)</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>The Pediatric Activity Index (PCDAI) has become the standard outcome measure in pediatric Crohn's disease (CD) clinical research. The Weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was developed to add weight to the items in the PCDAI and make it more feasible. In the wPCDAI, growth velocity, abdominal examination, and hematocrit are removed. The wPCDAI score can range from 0-125, with higher signifying severe disease activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in wPCDAI &gt;= 37.5</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>A change in wPCDAI &gt;= 37.5 indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of CD-related hospitalizations</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Hospitalization will be determined from the health care utilization information.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of clinical remission</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Clinical remission is weighted PCDAI &lt; 12.5 or Harvey-Bradshaw index (HBI) &lt;5. Rate of clinical remission will be described at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants achieving mucosal healing at each time point</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Mucosal healing is assessed using SES-CD score (0 or 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with steroid-free clinical remission at each time point</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>The proportion of participants with steroid-free clinical remission is assessed at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in weight z-score</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>Growth is assessed by monitoring changes in weight z-score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median percent change from baseline in high sensitivity C-reactive protein (hs-CRP)</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>The median percent change from baseline in hs-CRP is assessed at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessing Mucosal healing</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Mucosal healing is assessed using Simple Endoscopic Score for Cronh's Disease (SES-CD) score (0 or 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of steroid-free remission</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Steroid-free remission is defined as weighted PCDAI &lt; 12.5 or HBI &lt;5 and no daily intake of prednisone (whatever the route). Rate of steroid-free remission will be described at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with fistula remission (in participants with fistulizing CD at entry)</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Fistula remission is defined as closure for at least 2 consecutive visits of all fistulae that were draining at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Tanner's staging</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>Tanner's staging is used to assess growth and pubertal development.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with immunomodulator-free clinical remission at each time point</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>The proportion of participants with immunomodulator-free clinical remission is assessed at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of infectious events</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>The incidence rate of serious and non-serious opportunistic infections is assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of all-cause hospitalizations</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Hospitalization will be determined from the health care utilization information.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with steroid tapering at each time point (steroids daily dosing lower than at baseline)</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>The proportion of participants with steroid tapering i.e., steroids daily dosing lower than at baseline (week 0) is assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in height z-score</measure>
    <time_frame>From Month 0 to 12 years</time_frame>
    <description>Growth is assessed by monitoring changes in height z-score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with CD-related surgery</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>CD-related surgery includes subtotal colectomy with ileorectostomy, colectomy with ileo-anal pouch, Koch pouch, ileostomy, small bowel resection, and etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of CD- or drug-related hospitalizations</measure>
    <time_frame>Up to 12 years</time_frame>
    <description>Hospitalization will be determined from the health care utilization information.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">62</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Pediatric participants receiving adalimumab</arm_group_label>
    <description>Pediatric participants receiving adalimumab for CD in real-life conditions.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Participants are children and adolescents with Crohn's disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  With confirmed diagnosis of Crohn's disease&#xD;
&#xD;
          -  Adalimumab-naïve patient (a patient having received an anti-TNF other than adalimumab&#xD;
             may enter the study)&#xD;
&#xD;
          -  Starting a treatment with adalimumab&#xD;
&#xD;
          -  Guardian capable of and willing to grant authorization for use/disclosure of data&#xD;
             collected and patient able to comply with the requirements of the study protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with a history of treatment with adalimumab&#xD;
&#xD;
          -  Participants enrolled in a concomitant interventional clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>AbbVie Inc.</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud /ID# 152667</name>
      <address>
        <city>Pierre Benite CEDEX</city>
        <state>Auvergne-Rhone-Alpes</state>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud /ID# 152668</name>
      <address>
        <city>Pierre Benite CEDEX</city>
        <state>Auvergne-Rhone-Alpes</state>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Clocheville /ID# 152831</name>
      <address>
        <city>Tours</city>
        <state>Centre-Val De Loire</state>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Besancon - Jean Minjoz /ID# 154197</name>
      <address>
        <city>Besancon</city>
        <state>Doubs</state>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopitaux de Brabois Adultes /ID# 152729</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <state>Lorraine</state>
        <zip>54500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse /ID# 153251</name>
      <address>
        <city>Toulouse CEDEX 3</city>
        <state>Occitanie</state>
        <zip>31025</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Batiment Robert Debre /ID# 152665</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bordeaux-Hopital Pellegrin /ID# 154620</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu de Bordeaux Hopital /Id# 157926</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitai /ID# 155465</name>
      <address>
        <city>Caen</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Hopital d'Estaing /ID# 152664</name>
      <address>
        <city>Clermont Ferrand</city>
        <zip>63100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Jeanne de Flandre /Id# 155464</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de la Timone /ID# 160133</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Jacques Monod /ID# 152663</name>
      <address>
        <city>Montivillier</city>
        <zip>76290</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de la Source /ID# 159947</name>
      <address>
        <city>Orleans</city>
        <zip>45067</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de la Source /ID# 165534</name>
      <address>
        <city>Orleans</city>
        <zip>45067</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert Debre Hopital, FR /ID# 152666</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Armand Trousseau /Id# 152669</name>
      <address>
        <city>Paris</city>
        <zip>75571</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Armand Trousseau /Id# 157092</name>
      <address>
        <city>Paris</city>
        <zip>75571</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Necker Hopital, FR /ID# 152830</name>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Lyon Sud /Id# 152838</name>
      <address>
        <city>Pierre Benite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes - Hospital Sud /ID# 152730</name>
      <address>
        <city>Rennes</city>
        <zip>35203</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charles Nicolle Hosp chu rouen /ID# 152670</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charles Nicolle Hosp chu rouen /ID# 158688</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>https://www.abbvie.com/content/dam/abbvie-dotcom/clinical-trials/adalimumab_P15-759.pdf</url>
    <description>clinical study report synopsis</description>
  </link>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crohn's Disease</keyword>
  <keyword>Adalimumab</keyword>
  <keyword>Humira®</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03017014
org study id: P15-759
nct id: NCT03017014
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The primary objective of this study is to evaluate long-term effectiveness of adalimumab in
      pediatric participants starting a treatment for Crohn's disease in real life conditions,
      namely to describe the time to loss of clinical benefit in a time to event approach. Main
      secondary objectives are to describe growth and pubertal development and to describe
      long-term safety. The participants will be followed-up up to 10 years.
observational model: Cohort
time perspective: Prospective
measure: Time to loss of clinical benefit
time frame: Up to 12 years
description: Loss of clinical benefit will be defined as one of the following:
Loss of efficacy leading to adalimumab discontinuation or
Introduction / reinforcement of other immunosuppressants (ratio dose/weight) or
Introduction / reinforcement of corticosteroids (ratio dose/weight; reinforcement of corticosteroids are allowed within the 4 first months after start of adalimumab)
Introduction of enteral nutrition
CD-related surgery, discontinuation of adalimumab due to adverse event, death.
measure: Proportion of participants with dose escalation (dose and/or frequency of injections)
time frame: Up to 12 years
description: Dosing and/or frequency of injections is monitored to assess dose escalation.
measure: Median percent change from baseline in C-reactive protein (CRP)
time frame: From Month 0 to 12 years
description: The median percent change from baseline in CRP is assessed at each time point.
measure: Median percent change from baseline in calprotectin
time frame: From Month 0 to 12 years
description: The median percent change from baseline in calprotectin us assessed at each time point.
measure: Change from baseline in weighted Pediatric Crohn's Disease Activity Index (PCDAI)
time frame: From Month 0 to 12 years
description: The Pediatric Activity Index (PCDAI) has become the standard outcome measure in pediatric Crohn's disease (CD) clinical research. The Weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was developed to add weight to the items in the PCDAI and make it more feasible. In the wPCDAI, growth velocity, abdominal examination, and hematocrit are removed. The wPCDAI score can range from 0-125, with higher signifying severe disease activity.
measure: Change in wPCDAI >= 37.5
time frame: From Month 0 to 12 years
description: A change in wPCDAI >= 37.5 indicates improvement.
measure: Incidence rate of CD-related hospitalizations
time frame: Up to 12 years
description: Hospitalization will be determined from the health care utilization information.
measure: Rate of clinical remission
time frame: Up to 12 years
description: Clinical remission is weighted PCDAI < 12.5 or Harvey-Bradshaw index (HBI) <5. Rate of clinical remission will be described at each time point
measure: Proportion of participants achieving mucosal healing at each time point
time frame: Up to 12 years
description: Mucosal healing is assessed using SES-CD score (0 or 1).
measure: Proportion of participants with steroid-free clinical remission at each time point
time frame: Up to 12 years
description: The proportion of participants with steroid-free clinical remission is assessed at each time point.
measure: Change in weight z-score
time frame: From Month 0 to 12 years
description: Growth is assessed by monitoring changes in weight z-score.
measure: Median percent change from baseline in high sensitivity C-reactive protein (hs-CRP)
time frame: From Month 0 to 12 years
description: The median percent change from baseline in hs-CRP is assessed at each time point.
measure: Assessing Mucosal healing
time frame: Up to 12 years
description: Mucosal healing is assessed using Simple Endoscopic Score for Cronh's Disease (SES-CD) score (0 or 1).
measure: Rate of steroid-free remission
time frame: Up to 12 years
description: Steroid-free remission is defined as weighted PCDAI < 12.5 or HBI <5 and no daily intake of prednisone (whatever the route). Rate of steroid-free remission will be described at each time point.
measure: Proportion of participants with fistula remission (in participants with fistulizing CD at entry)
time frame: Up to 12 years
description: Fistula remission is defined as closure for at least 2 consecutive visits of all fistulae that were draining at baseline
measure: Change in Tanner's staging
time frame: From Month 0 to 12 years
description: Tanner's staging is used to assess growth and pubertal development.
measure: Proportion of participants with immunomodulator-free clinical remission at each time point
time frame: Up to 12 years
description: The proportion of participants with immunomodulator-free clinical remission is assessed at each time point.
measure: Incidence rate of infectious events
time frame: Up to 12 years
description: The incidence rate of serious and non-serious opportunistic infections is assessed.
measure: Incidence rate of all-cause hospitalizations
time frame: Up to 12 years
description: Hospitalization will be determined from the health care utilization information.
measure: Proportion of participants with steroid tapering at each time point (steroids daily dosing lower than at baseline)
time frame: Up to 12 years
description: The proportion of participants with steroid tapering i.e., steroids daily dosing lower than at baseline (week 0) is assessed.
measure: Change in height z-score
time frame: From Month 0 to 12 years
description: Growth is assessed by monitoring changes in height z-score
measure: Proportion of participants with CD-related surgery
time frame: Up to 12 years
description: CD-related surgery includes subtotal colectomy with ileorectostomy, colectomy with ileo-anal pouch, Koch pouch, ileostomy, small bowel resection, and etc.
measure: Incidence rate of CD- or drug-related hospitalizations
time frame: Up to 12 years
description: Hospitalization will be determined from the health care utilization information.
arm group label: Pediatric participants receiving adalimumab
description: Pediatric participants receiving adalimumab for CD in real-life conditions.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
last name: AbbVie Inc.
role: Study Director
affiliation: AbbVie
facility: 
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country: France
url: https://www.abbvie.com/content/dam/abbvie-dotcom/clinical-trials/adalimumab_P15-759.pdf
description: clinical study report synopsis
responsible party type: Sponsor
mesh term: Crohn Disease
sharing ipd: Undecided