<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/NCT01674413</url>
  </required_header>
  <id_info>
    <org_study_id>Abbott IMM 10-0105</org_study_id>
    <secondary_id>Abbott IMM 10-0105</secondary_id>
    <nct_id>NCT01674413</nct_id>
  </id_info>
  <brief_title>Calprotectin-Directed Humira® Maintenance Therapy (CADHUM)</brief_title>
  <acronym>CADHUM</acronym>
  <official_title>Calprotectin-Directed Humira® Maintenance Therapy, a Double-blind, Double-dummy, Randomized Controlled Trial in Crohn's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter Higgins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study that invites adults with Crohn's disease and have been responding well to&#xD;
      Adalimumab (Humira ®) for at least 6 months. Patients frequently discontinue maintenance&#xD;
      medications in Crohn's disease, particularly when in remission. Patients want to know that&#xD;
      they truly need to take a medication, yet they don't want to have flares. The purpose of this&#xD;
      study is to see that if we monitor the patient, along with looking at changes in their stool&#xD;
      samples, we can safely stop the maintenance medication Adalimumab for up to 48 weeks, or add&#xD;
      as-needed dosing only, and keep them in remission.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients frequently discontinue maintenance medications in Crohn's disease, particularly when&#xD;
      in remission. Patients want to know that they truly need to take a medication, yet they don't&#xD;
      want to have flares. As a biomarker, fecal calprotectin &lt; 167 has a 100% negative predictive&#xD;
      value for flare within the next 12 weeks (Gisbert, 2009). Adalimumab has low antigenicity,&#xD;
      and can be safely stopped and restarted later with good clinical effect (Colombel, 2007).&#xD;
      Patients want intermittent therapy, if it can be delivered in a timely fashion when&#xD;
      pre-clinical inflammation starts, in order to avoid clinically-significant flares. This study&#xD;
      will combine monitoring for pre-clinical inflammation with fecal calprotectin and as-needed&#xD;
      dosing with Adalimumab to maintain remission in patients who have obtained remission with&#xD;
      Adalimumab. This will be compared to two comparator arms: standard maintenance therapy and&#xD;
      complete cessation of therapy (Step-Down approach).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Unable to recruit; all patients interested simply wanted to stop medication&#xD;
  </why_stopped>
  <start_date>October 2013</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 3</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>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Time in Remission (PTIR) in PRNLOAD vs. Placebo arms</measure>
    <time_frame>48 weeks</time_frame>
    <description>Determine whether adding as-needed q 12 weeks Adalimumab re-loading (160 mg/80 mg) when FCP ≥167 mcg/gram of stool can improve the maintenance of remission in Crohn's disease patients who stop Adalimumab therapy (PRNLOAD Arm) compared to the placebo arm. Endpoint: Percent time in remission (q 4 week evaluation for 48 weeks).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Time in Remission MAINT vs. PRNLOAD</measure>
    <time_frame>48 weeks</time_frame>
    <description>Compare the percent of monitoring visits in which the subject is in remission in each arm between the MAINT and PRNLOAD arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Time in Remission MAINT vs. PBO</measure>
    <time_frame>48 weeks.</time_frame>
    <description>Compare the percent of monitoring visits in which the subject is in remission in each arm between the MAINT and PBO arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Strict Biologic Remission Rates</measure>
    <time_frame>48 weeks</time_frame>
    <description>Percent of visits with strict biologic remission (FCP &lt;50 and CRP &lt;0.5) with 3 comparisons: PRNLOAD vs. PBO, MAINT vs. PRNLOAD, MAINT vs. PBO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject acceptability</measure>
    <time_frame>48 weeks</time_frame>
    <description>Measure subject acceptability of repeated stool sampling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject preference</measure>
    <time_frame>48 weeks</time_frame>
    <description>Measure subject preference for the MAINT versus PRNLOAD regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Equivalence of Percent Time in Remission</measure>
    <time_frame>48 weeks</time_frame>
    <description>Compare percent time in remission (CDAI &lt;150) over 48 weeks, evaluation every 4 weeks across 3 arms (chi square test).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Average CDAI</measure>
    <time_frame>48 weeks</time_frame>
    <description>Compare average CDAI over 48 weeks, evaluation every 4 weeks across 3 arms (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of average IBDQ</measure>
    <time_frame>48 weeks</time_frame>
    <description>Compare average IBDQ over 48 weeks, evaluation every 4 weeks across 3 arms (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of average FCP</measure>
    <time_frame>48 weeks</time_frame>
    <description>Compare average FCP over 48 weeks, evaluation every 12 weeks across 3 arms (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of average CRP</measure>
    <time_frame>48 weeks</time_frame>
    <description>Compare average CRP over 48 weeks, evaluation every 12 weeks across 3 arms (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Rates of Hospitalization</measure>
    <time_frame>48 Weeks</time_frame>
    <description>Comparison of Rates of Hospitalization across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Rates of Emergency Department visits</measure>
    <time_frame>48 Weeks</time_frame>
    <description>Comparison of Rates of Emergency Department visits across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Rates of Physician visits</measure>
    <time_frame>48 Weeks</time_frame>
    <description>Comparison of Rates of Physician visits across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of mg prednisone prescribed</measure>
    <time_frame>48 Weeks</time_frame>
    <description>Comparison of average milligrams of prednisone prescribed across all 3 arms - over 48 weeks (ANOVA).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Anti-Adalimumab antibodies</measure>
    <time_frame>0, 48 weeks</time_frame>
    <description>Measure anti-Adalimumab antibody titers in patients at week 0 and 48 weeks (or exit visit). Compare average titers across 3 arms (ANOVA)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Placebo/Step-Down</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 syringe of placebo SC q 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PRNLOAD Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Adalimumab 40 mg q 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adalimumab</intervention_name>
    <description>Adalimumab 40 mg q 2 weeks, with placebo loading of 3 syringes/1 syringe at Weeks 0/2, 12/14, 24/26, and 36/38</description>
    <arm_group_label>Maintenance Arm</arm_group_label>
    <other_name>Humira</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adalimumab PRN</intervention_name>
    <description>160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38), with&#xD;
PRNLOADing of 160 mg/80 mg Adalimumab at Weeks 12/14, 24/26, or 36/38 if most recent FCP is ≥167 mcg/gram of stool,&#xD;
Or, placebo loading of 4 syringes/2 syringes at Weeks 12/14, 24/26, and 36/38 if most recent FCP is &lt; 167 mcg/gram of stool.</description>
    <arm_group_label>PRNLOAD Arm</arm_group_label>
    <other_name>Humira</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1 syringe of placebo SC q 2 weeks, with additional placebo loading of 3 syringes/1 syringe at Weeks 0/2, 12/14, 24/26, and 36/38 Weeks.</description>
    <arm_group_label>Placebo/Step-Down</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women 18 years of age or older at the time of informed consent.&#xD;
&#xD;
          2. Crohn's disease confirmed by endoscopy with biopsies.&#xD;
&#xD;
          3. On maintenance Adalimumab at a dose of 40 mg SC q 2 weeks without concomitant&#xD;
             immunosuppressive therapy.&#xD;
&#xD;
          4. Must be in clinical remission (CDAI &lt;150) at the baseline/randomization (Week 0) visit&#xD;
             and biologic remission (both CRP &lt;0.8 and FCP &lt;167)at Week 0.&#xD;
&#xD;
          5. Prior medication for Crohn's disease may include one of the following and must have&#xD;
             been stopped with wash out periods: Methotrexate, Azathioprine, 6-Mercaptopurine,&#xD;
             Tacrolimus, Steroids.&#xD;
&#xD;
          6. Negative for TB, Hepatitis B-negative, and negative stool for Clostridium difficile.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Unable to consent for themselves.&#xD;
&#xD;
          2. Are prisoners, students or employees of the investigators, or mentally incapacitated.&#xD;
&#xD;
          3. Are unwilling to complete this 48 week study, provide stool samples throughout, or&#xD;
             unwilling to undergo multiple venipunctures.&#xD;
&#xD;
          4. Have a current infection with Clostridium difficile, clinically-significant intestinal&#xD;
             stricture, history of allergy, or adverse reaction, to Adalimumab, history of&#xD;
             sensitivity to latex.&#xD;
&#xD;
          5. Are currently using steroids or systemic immunomodulators (MTX, AZA, 6-MP, or&#xD;
             Tacrolimus), or have used another biologic medication in the past 12 weeks other than&#xD;
             Adalimumab, or have current or past use of Kineret® (Anakinra) or Tysabri®&#xD;
             (natalizumab).&#xD;
&#xD;
          6. Have received any live bacterial or viral vaccinations ≤ 12 weeks prior to Week 0 and&#xD;
             must not receive 12 months after study as well as BCG vaccination&#xD;
&#xD;
          7. Are known to have congestive heart failure.&#xD;
&#xD;
          8. Have a history of, or ongoing chronic or recurrent infectious disease, including but&#xD;
             not limited to chronic renal, chest infection (i.e. bronchiectasis) or urinary tract&#xD;
             infection (i.e. recurrent pyelonephritis) or open, draining, or infected skin wounds&#xD;
             or ulcers.&#xD;
&#xD;
          9. Have evidence of current clinically active and important infection.&#xD;
&#xD;
         10. Have or ever had a non-tuberculous mycobacterium infection or serious opportunistic&#xD;
             infection (i.e. cytomegalovirus, Pneumocystis carinii, aspergillosis).&#xD;
&#xD;
         11. Are known to be infected with HIV, Hepatitis B, or Hepatitis C.&#xD;
&#xD;
         12. Have severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine,&#xD;
             pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and&#xD;
             symptoms thereof.&#xD;
&#xD;
         13. Have a known history of lymphoproliferative disease including lymphoma. Have a history&#xD;
             of certain malignancies within five years of screening.&#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>Peter D Higgins, MD, PhD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Health System</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>May 23, 2017</last_update_submitted>
  <last_update_submitted_qc>May 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Peter Higgins</investigator_full_name>
    <investigator_title>M.D., Ph.D., MSc. Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Crohn's Disease</keyword>
  <keyword>Crohn's</keyword>
  <keyword>Crohns</keyword>
  <keyword>Inflammatory Bowel Disease</keyword>
  <keyword>IBD</keyword>
  <keyword>Humira</keyword>
  <keyword>Adalimumab</keyword>
  <keyword>Adalimumab injection</keyword>
  <keyword>Higgins</keyword>
  <keyword>Calprotectin</keyword>
  <keyword>biomarkers</keyword>
  <keyword>Gastroenterology</keyword>
  <keyword>University of Michigan</keyword>
  <keyword>U of M</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</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>
    <ipd_description>no data collected</ipd_description>
  </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/NCT01674413
org study id: Abbott IMM 10-0105
secondary id: Abbott IMM 10-0105
nct id: NCT01674413
lead sponsor: 
collaborator: 
has dmc: No
This is a study that invites adults with Crohn's disease and have been responding well to
      Adalimumab (Humira ®) for at least 6 months. Patients frequently discontinue maintenance
      medications in Crohn's disease, particularly when in remission. Patients want to know that
      they truly need to take a medication, yet they don't want to have flares. The purpose of this
      study is to see that if we monitor the patient, along with looking at changes in their stool
      samples, we can safely stop the maintenance medication Adalimumab for up to 48 weeks, or add
      as-needed dosing only, and keep them in remission.
Patients frequently discontinue maintenance medications in Crohn's disease, particularly when
      in remission. Patients want to know that they truly need to take a medication, yet they don't
      want to have flares. As a biomarker, fecal calprotectin < 167 has a 100% negative predictive
      value for flare within the next 12 weeks (Gisbert, 2009). Adalimumab has low antigenicity,
      and can be safely stopped and restarted later with good clinical effect (Colombel, 2007).
      Patients want intermittent therapy, if it can be delivered in a timely fashion when
      pre-clinical inflammation starts, in order to avoid clinically-significant flares. This study
      will combine monitoring for pre-clinical inflammation with fecal calprotectin and as-needed
      dosing with Adalimumab to maintain remission in patients who have obtained remission with
      Adalimumab. This will be compared to two comparator arms: standard maintenance therapy and
      complete cessation of therapy (Step-Down approach).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Percent Time in Remission (PTIR) in PRNLOAD vs. Placebo arms
time frame: 48 weeks
description: Determine whether adding as-needed q 12 weeks Adalimumab re-loading (160 mg/80 mg) when FCP ≥167 mcg/gram of stool can improve the maintenance of remission in Crohn's disease patients who stop Adalimumab therapy (PRNLOAD Arm) compared to the placebo arm. Endpoint: Percent time in remission (q 4 week evaluation for 48 weeks).
measure: Percent Time in Remission MAINT vs. PRNLOAD
time frame: 48 weeks
description: Compare the percent of monitoring visits in which the subject is in remission in each arm between the MAINT and PRNLOAD arms.
measure: Percent Time in Remission MAINT vs. PBO
time frame: 48 weeks.
description: Compare the percent of monitoring visits in which the subject is in remission in each arm between the MAINT and PBO arms.
measure: Strict Biologic Remission Rates
time frame: 48 weeks
description: Percent of visits with strict biologic remission (FCP <50 and CRP <0.5) with 3 comparisons: PRNLOAD vs. PBO, MAINT vs. PRNLOAD, MAINT vs. PBO
measure: Subject acceptability
time frame: 48 weeks
description: Measure subject acceptability of repeated stool sampling.
measure: Subject preference
time frame: 48 weeks
description: Measure subject preference for the MAINT versus PRNLOAD regimen.
measure: Equivalence of Percent Time in Remission
time frame: 48 weeks
description: Compare percent time in remission (CDAI <150) over 48 weeks, evaluation every 4 weeks across 3 arms (chi square test).
measure: Comparison of Average CDAI
time frame: 48 weeks
description: Compare average CDAI over 48 weeks, evaluation every 4 weeks across 3 arms (ANOVA).
measure: Comparison of average IBDQ
time frame: 48 weeks
description: Compare average IBDQ over 48 weeks, evaluation every 4 weeks across 3 arms (ANOVA).
measure: Comparison of average FCP
time frame: 48 weeks
description: Compare average FCP over 48 weeks, evaluation every 12 weeks across 3 arms (ANOVA).
measure: Comparison of average CRP
time frame: 48 weeks
description: Compare average CRP over 48 weeks, evaluation every 12 weeks across 3 arms (ANOVA).
measure: Comparison of Rates of Hospitalization
time frame: 48 Weeks
description: Comparison of Rates of Hospitalization across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).
measure: Comparison of Rates of Emergency Department visits
time frame: 48 Weeks
description: Comparison of Rates of Emergency Department visits across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).
measure: Comparison of Rates of Physician visits
time frame: 48 Weeks
description: Comparison of Rates of Physician visits across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).
measure: Comparison of mg prednisone prescribed
time frame: 48 Weeks
description: Comparison of average milligrams of prednisone prescribed across all 3 arms - over 48 weeks (ANOVA).
measure: Anti-Adalimumab antibodies
time frame: 0, 48 weeks
description: Measure anti-Adalimumab antibody titers in patients at week 0 and 48 weeks (or exit visit). Compare average titers across 3 arms (ANOVA)
arm group label: Placebo/Step-Down
arm group type: Placebo Comparator
description: 1 syringe of placebo SC q 2 weeks.
arm group label: PRNLOAD Arm
arm group type: Active Comparator
description: 160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38)
arm group label: Maintenance Arm
arm group type: Active Comparator
description: Adalimumab 40 mg q 2 weeks.
intervention type: Drug
intervention name: Adalimumab
description: Adalimumab 40 mg q 2 weeks, with placebo loading of 3 syringes/1 syringe at Weeks 0/2, 12/14, 24/26, and 36/38
arm group label: Maintenance Arm
other name: Humira
intervention type: Drug
intervention name: Adalimumab PRN
description: 160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38), with
PRNLOADing of 160 mg/80 mg Adalimumab at Weeks 12/14, 24/26, or 36/38 if most recent FCP is ≥167 mcg/gram of stool,
Or, placebo loading of 4 syringes/2 syringes at Weeks 12/14, 24/26, and 36/38 if most recent FCP is < 167 mcg/gram of stool.
arm group label: PRNLOAD Arm
other name: Humira
intervention type: Drug
intervention name: Placebo
description: 1 syringe of placebo SC q 2 weeks, with additional placebo loading of 3 syringes/1 syringe at Weeks 0/2, 12/14, 24/26, and 36/38 Weeks.
arm group label: Placebo/Step-Down
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter D Higgins, MD, PhD, MSc
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Michigan
investigator full name: Peter Higgins
investigator title: M.D., Ph.D., MSc. Assistant Professor of Medicine
mesh term: Crohn Disease
mesh term: Adalimumab
sharing ipd: No
ipd description: no data collected