<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/NCT03261102</url>
  </required_header>
  <id_info>
    <org_study_id>MP-37-2017-2793</org_study_id>
    <nct_id>NCT03261102</nct_id>
  </id_info>
  <brief_title>TDM Guided Early Optimization of ADAL in Crohn's Disease</brief_title>
  <official_title>Therapeutic Drug Monitoring Guided Early Optimization of Adalimumab in Crohn's Disease; A Randomized Open Label Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>waqqas.afif</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</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>
      To investigate the influence of early therapeutic drug monitoring and dose optimization on&#xD;
      disease outcome in Crohn's patients treated with Adalimumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an investigator initiated randomized open label study. This study is designed to&#xD;
      compare whether increasing the dose of adalimumab based on the level the drug in the blood to&#xD;
      a target level early in the treatment course would lead to better outcomes for patients as&#xD;
      compared to the standard doses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 17, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</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>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Some of the participants, care providers and investigators will eventually, in the course of the study, have knowledge of the arm they were assigned.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of subjects who achieved remission</measure>
    <time_frame>Week 12</time_frame>
    <description>Clinical remission will be scored by a Harvey-Bradshaw Index &lt; 5 AND Biochemical remission will be scored by C-reactive protein &lt; 5 mg/l OR Fecal calprotectin &lt;250 μg/g (combination endpoint)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who achieved clinical response</measure>
    <time_frame>From Week 0 to Week 12</time_frame>
    <description>Clinical response will be evaluated by a decreased in Harvey-Bradshaw Index score AND a decreased level of C-reactive protein OR Fecal calprotectin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Therapeutic drug monitoring</measure>
    <time_frame>At Week 8, 12</time_frame>
    <description>Adalimumab drug concentration at week 8 and 12 AND proportion of subjects with antibody to Adalimumab at Week 8 and 12 on the rate i. Clinical response/remission (HBI&lt;5) ii. Biochemical response/remission (CRP within normal reference range) iii. Endoscopic response (SES-CD reduction of ≥50% from baseline) / remission (SES-CD ≤3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of steroid free subjects</measure>
    <time_frame>At Week 12</time_frame>
    <description>Steroid free defined as patients being steroid free at Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjects well-being</measure>
    <time_frame>From Week 0 to Week 12</time_frame>
    <description>Subjects well-being will be scored using the validated questionnaire Short inflammatory bowel disease questionnaire (SIBDQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of complications</measure>
    <time_frame>12 weeks</time_frame>
    <description>Rates of complications, including hospitalization, surgery, adverse reaction, and corticosteroid use.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Crohn Disease</condition>
  <condition>Drug Monitoring</condition>
  <condition>Inflammatory Bowel Diseases</condition>
  <arm_group>
    <arm_group_label>Standard clinical care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Adalimumab induction as per standard clinical care:&#xD;
Week 0: 160 mg SC&#xD;
Week 2: 80 mg SC&#xD;
Followed by 40 mg SC every 2 weeks' maintenance therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active optimization</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Same as Standard clinical care Arm, except:&#xD;
If ADAL trough ≤15 μg/ml, dose escalation with 80 mg SC at week 6 followed by 40 mg SC every week&#xD;
If ADAL trough &gt;15 μg/ml, no dose escalation and continued standard of care dosing</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab</intervention_name>
    <arm_group_label>Active optimization</arm_group_label>
    <arm_group_label>Standard clinical care</arm_group_label>
    <other_name>Humira</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 or older.&#xD;
&#xD;
          -  Crohn's disease diagnosed based on standard objective methodology (clinical,&#xD;
             biochemical, endoscopic, histological and radiological correlation).&#xD;
&#xD;
          -  Active disease based on Harvey Bradshaw Index (HBI &gt;5) and elevated C-reactive protein&#xD;
             (CRP) (&gt;normal reference range for local laboratory) OR fecal calprotectin (FCP) (&gt;250&#xD;
             µg/g)&#xD;
&#xD;
          -  Due to commence treatment with ADAL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe co-existing cardiopulmonary, hepatic, renal, neurologic, or rheumatologic&#xD;
             disease.&#xD;
&#xD;
          -  History of active HIV, hepatitis B or C infection,&#xD;
&#xD;
          -  Patients with ileostomy/colostomy, ileal-pouch anal anastomosis or severe perianal&#xD;
             fistulising disease.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prior exposure to ADAL&#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>Waqqas Afif, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carolyne Lemieux, BN, RN</last_name>
    <phone>(514) 934-1934</phone>
    <phone_ext>45699</phone_ext>
    <email>carolyne.lemieux@muhc.mcgill.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Meaghan Smith, RN</last_name>
    <phone>(514) 934-1934</phone>
    <phone_ext>45699</phone_ext>
    <email>meghan.smith@muhc.mcgill.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Calgary Medical Center (UCMC)</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>The University of British Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 1Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre (LHSC) University Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital, IBD Centre of Excellence</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Melissa Tessier</last_name>
      <phone>(613) 737-8899</phone>
      <phone_ext>73035</phone_ext>
      <email>metessier@ohri.ca</email>
    </contact>
    <investigator>
      <last_name>Sanjay Murthy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>McGill University Hospital Center (MUHC)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3G 1A4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carolyne Lemieux, BN, RN</last_name>
      <phone>(514) 934-1934</phone>
      <phone_ext>45699</phone_ext>
      <email>carolyne.lemieux@muhc.mcgill.ca</email>
    </contact>
    <contact_backup>
      <last_name>Meaghan Smith, RN</last_name>
      <phone>(514) 934-1934</phone>
      <phone_ext>45699</phone_ext>
      <email>meaghan.smith@muhc.mcgill.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Waqqas Afif, MD, FRCPC</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Talat Bessissow, MDCM, FRCPC</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alain Bitton, MDCM, FRCPC</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Che-yung Jeff Chao, MBChB, FRACP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sophie Restellini-Kherad</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Sherbrooke (CHUS)</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1G 2E8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chantal Guillet</last_name>
      <phone>(819) 346-1110</phone>
      <phone_ext>12812</phone_ext>
      <email>cguillet.chus@ssss.gouv.qc.ca</email>
    </contact>
    <investigator>
      <last_name>Joannie Ruel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>March 31, 2023</last_update_submitted>
  <last_update_submitted_qc>March 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>waqqas.afif</investigator_full_name>
    <investigator_title>Dr. Waqqas Afif MD, FRCPC</investigator_title>
  </responsible_party>
  <keyword>IBD</keyword>
  <keyword>Crohn</keyword>
  <keyword>adalimumab</keyword>
  <keyword>ADAL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</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/NCT03261102
org study id: MP-37-2017-2793
nct id: NCT03261102
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To investigate the influence of early therapeutic drug monitoring and dose optimization on
      disease outcome in Crohn's patients treated with Adalimumab.
This is an investigator initiated randomized open label study. This study is designed to
      compare whether increasing the dose of adalimumab based on the level the drug in the blood to
      a target level early in the treatment course would lead to better outcomes for patients as
      compared to the standard doses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Some of the participants, care providers and investigators will eventually, in the course of the study, have knowledge of the arm they were assigned.
measure: Proportion of subjects who achieved remission
time frame: Week 12
description: Clinical remission will be scored by a Harvey-Bradshaw Index < 5 AND Biochemical remission will be scored by C-reactive protein < 5 mg/l OR Fecal calprotectin <250 μg/g (combination endpoint)
measure: Proportion of subjects who achieved clinical response
time frame: From Week 0 to Week 12
description: Clinical response will be evaluated by a decreased in Harvey-Bradshaw Index score AND a decreased level of C-reactive protein OR Fecal calprotectin
measure: Therapeutic drug monitoring
time frame: At Week 8, 12
description: Adalimumab drug concentration at week 8 and 12 AND proportion of subjects with antibody to Adalimumab at Week 8 and 12 on the rate i. Clinical response/remission (HBI<5) ii. Biochemical response/remission (CRP within normal reference range) iii. Endoscopic response (SES-CD reduction of ≥50% from baseline) / remission (SES-CD ≤3)
measure: Proportion of steroid free subjects
time frame: At Week 12
description: Steroid free defined as patients being steroid free at Week 12
measure: Subjects well-being
time frame: From Week 0 to Week 12
description: Subjects well-being will be scored using the validated questionnaire Short inflammatory bowel disease questionnaire (SIBDQ)
measure: Rates of complications
time frame: 12 weeks
description: Rates of complications, including hospitalization, surgery, adverse reaction, and corticosteroid use.
arm group label: Standard clinical care
arm group type: Active Comparator
description: Adalimumab induction as per standard clinical care:
Week 0: 160 mg SC
Week 2: 80 mg SC
Followed by 40 mg SC every 2 weeks' maintenance therapy
arm group label: Active optimization
arm group type: Active Comparator
description: Same as Standard clinical care Arm, except:
If ADAL trough ≤15 μg/ml, dose escalation with 80 mg SC at week 6 followed by 40 mg SC every week
If ADAL trough >15 μg/ml, no dose escalation and continued standard of care dosing
intervention type: Biological
intervention name: Adalimumab
arm group label: Active optimization
arm group label: Standard clinical care
other name: Humira
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Waqqas Afif, MD, FRCPC
role: Principal Investigator
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Carolyne Lemieux, BN, RN
phone: (514) 934-1934
phone ext: 45699
email: carolyne.lemieux@muhc.mcgill.ca
last name: Meaghan Smith, RN
phone: (514) 934-1934
phone ext: 45699
email: meghan.smith@muhc.mcgill.ca
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: waqqas.afif
investigator title: Dr. Waqqas Afif MD, FRCPC
mesh term: Crohn Disease
mesh term: Inflammatory Bowel Diseases
mesh term: Adalimumab
sharing ipd: No