<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/NCT02249078</url>
  </required_header>
  <id_info>
    <org_study_id>E6011-A001-102</org_study_id>
    <nct_id>NCT02249078</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 3 Subcutaneous and 1 Intravenous Dose of E6011 in Subjects With Active Crohn's Disease</brief_title>
  <official_title>A Multicenter, Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Sequential-Cohort, Multiple-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 3 Subcutaneous and 1 Intravenous Dose of E6011 in Subjects With Active Crohn's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, Phase 1b, randomized, double-blind, placebo-controlled,&#xD;
      sequential-cohort, multiple ascending dose (MAD) study to evaluate the safety, tolerability,&#xD;
      pharmacokinetics (PK), and pharmacodynamics (PD) of 3 subcutaneous and 1 intravenous dose of&#xD;
      E6011 in subjects with active Crohn's disease (CD). Thirty-two subjects will be randomized to&#xD;
      one of 4 dose cohorts (8 per cohort) and will receive E6011 or placebo for 10 weeks. The&#xD;
      first 3 cohorts will receive E6011 or placebo via subcutaneous injection and the last cohort&#xD;
      will receive E6011 or placebo by intravenous injection. The ratio of E6011 to placebo within&#xD;
      each cohort will be 3:1. The study has 2 phases: Prerandomization and Randomization.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Anticipated">April 2016</completion_date>
  <primary_completion_date type="Anticipated">March 2016</primary_completion_date>
  <phase>Phase 1</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of the short-term safety and tolerability of E6011</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The short-term safety and tolerability of subcutaneous (SC) and intravenous (IV) doses of E6011 compared to placebo in subjects with active CD. Safety assessments will consist of monitoring and recording all AEs and SAEs; regulatory monitoring of hematology, blood chemistry, and urine values; periodic measurement vital signs and ECGs; and performance of physical examinations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of E6011 measured over time in blood samples.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number and percentage of participants with anti-E6011 antibodies detected in blood samples over time.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of screen positives, confirm positives, and relative anti-E6011 levels measured in blood samples from participants.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in the percentage of immunohistochemical staining for the CX3CR1+ protein in intestinal tissue over time.</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg subcutaneous once every 2 weeks with initial double dose (200 mg total)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg subcutaneous once every 2 weeks with initial double dose (400 mg total)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>400 mg subcutaneous once every 2 weeks with initial double dose (800 mg total)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg/kg IV at Day 1, Day 8, Day 15, and every 2 weeks thereafter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 2-mL vial solution for injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E6011</intervention_name>
    <description>E6011 solution for injection</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo 2-mL vial solution for injection</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Subjects must meet all of the following criteria to be included in this study:&#xD;
&#xD;
          1. Male or female subjects age greater than or equal to 18 years old at the time of&#xD;
             informed consent&#xD;
&#xD;
          2. Confirmed diagnosis of CD, with at least one documented lesion within the reach of a&#xD;
             colonoscope (terminal ileal or ileo-colonic or colonic) from a previous colonoscopy,&#xD;
             for a minimum duration of 6 months at the time of screening&#xD;
&#xD;
          3. Active CD with a CD activity index (CDAI) score greater than or equal to 220 and less&#xD;
             than or equal to 450&#xD;
&#xD;
          4. Colonoscopic evidence of CD involvement with active inflammation of terminal ileum&#xD;
             and/or colon at Screening (performed only in subjects who have otherwise met all of&#xD;
             the inclusion and none of the exclusion criteria)&#xD;
&#xD;
          5. Inadequate response to, loss of response to, or intolerance of at least one of the&#xD;
             following agents as defined below:&#xD;
&#xD;
               -  Immunomodulators:&#xD;
&#xD;
               -  Signs and symptoms of persistently active disease despite a history of at least&#xD;
                  one 8-week regimen of oral azathioprine (AZA) (greater than or equal to 1.5&#xD;
                  mg/kg) or 6-mercaptopurine (6-MP) mg/kg (greater than or equal to 0.75 mg/kg) OR&#xD;
&#xD;
               -  Signs and symptoms of persistently active disease despite a history of at least&#xD;
                  one 8-week regimen of methotrexate (MTX) (greater than or equal to 12.5 mg/week)&#xD;
&#xD;
               -  History of intolerance to at least 1 immunomodulator (including, but not limited&#xD;
                  to) nausea/vomiting, abdominal pain, pancreatitis, liver function test (LFT)&#xD;
                  abnormalities, lymphopenia, thiopurine methyltransferase (TPMT) genetic mutation,&#xD;
                  infection&#xD;
&#xD;
               -  Tumor Necrosis Factor (TNF)-alpha antagonists:&#xD;
&#xD;
               -  Signs and symptoms of persistently active disease despite a history of at least&#xD;
                  one 4-week induction regimen of one of the following agents:&#xD;
&#xD;
               -  Infliximab: 5 mg/kg IV, 2 doses at least 2 weeks apart&#xD;
&#xD;
               -  Adalimumab: one 80 mg SC dose followed by one 40-mg dose at least 2 weeks apart&#xD;
&#xD;
               -  Certolizumab pegol: 400 mg SC dose, 2 doses at least 2 weeks apart OR&#xD;
&#xD;
               -  Recurrence of symptoms during scheduled maintenance dosing following prior&#xD;
                  clinical benefit (discontinuation despite clinical benefit does not qualify)&#xD;
&#xD;
               -  History of intolerance to at least 1 TNF antagonist (including, but not limited&#xD;
                  to infusion-related reaction, demyelination, congestive heart failure, infection)&#xD;
&#xD;
          6. C-reactive protein greater than or equal to 5 mg/L at screening or fecal calprotectin&#xD;
             greater than or equal to 250 ug/g&#xD;
&#xD;
          7. Females must not be breastfeeding or pregnant at Screening (as documented by a&#xD;
             negative beta-human chorionic gonadotropin [B-hCG]). A separate baseline assessment is&#xD;
             required if a negative screening pregnancy test was obtained more than 72 hours before&#xD;
             the first dose of study drug.&#xD;
&#xD;
          8. Females of childbearing potential must not have had unprotected sexual intercourse&#xD;
             within 30 days before study entry and must agree to use a highly effective method of&#xD;
             contraception (eg, total abstinence, an intrauterine device, a double-barrier method&#xD;
             [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral&#xD;
             contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout&#xD;
             the entire study period and for 70 days after study drug discontinuation. If currently&#xD;
             abstinent, the subject must agree to use a double-barrier method as described above if&#xD;
             she becomes sexually active during the study period or for 70 days after study drug&#xD;
             discontinuation. Females who are using hormonal contraceptives must have been on a&#xD;
             stable dose of the same hormonal contraceptive product for at least 4 weeks before&#xD;
             dosing and must continue to use the same contraceptive during the study and for 70&#xD;
             days after study drug discontinuation. All females will be considered to be of&#xD;
             childbearing potential unless they are postmenopausal (amenorrheic for at least 12&#xD;
             consecutive months, in the appropriate age group, and without other known or suspected&#xD;
             cause) or have been sterilized surgically (ie, bilateral tubal ligation, total&#xD;
             hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before&#xD;
             dosing).&#xD;
&#xD;
          9. Provide written informed consent&#xD;
&#xD;
         10. Willing and able to comply with all aspects of the protocol&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Subjects who meet any of the following criteria will be excluded from this study:&#xD;
&#xD;
          1. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal&#xD;
             [other than CD], renal disease, active infection, vasculitides) that in the opinion of&#xD;
             the investigator(s) could affect the patient's safety or interfere with the study&#xD;
             assessments&#xD;
&#xD;
          2. Any neurologic abnormality at screening&#xD;
&#xD;
          3. A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated&#xD;
             ECG at Screening&#xD;
&#xD;
          4. History of any severe allergy&#xD;
&#xD;
          5. Scheduled for surgery during planned participation in the study&#xD;
&#xD;
          6. Previous ileo-colonic resections or presence of an ostomy&#xD;
&#xD;
          7. Presence of active fistulizing CD&#xD;
&#xD;
          8. Total parenteral nutrition (TPN) or enema for treating CD within 2 weeks before&#xD;
             Screening&#xD;
&#xD;
          9. Treatment with adalimumab or certolizumab within 2 weeks before Screening&#xD;
&#xD;
         10. Treatment with infliximab within 4 weeks (or 8 weeks if subjects received 10 mg/kg)&#xD;
             before Screening&#xD;
&#xD;
         11. Treatment with vedolizumab (in case of approval or off-label use) or any other&#xD;
             monoclonal antibody within 8 weeks before starting the study treatment&#xD;
&#xD;
         12. History of treatment with natalizumab&#xD;
&#xD;
         13. Changes in dose of 5-aminosalicylic acid, 6-MP, MTX, and AZA therapy within 4 weeks of&#xD;
             Screening&#xD;
&#xD;
         14. Doses of greater than 30 mg/day of prednisone or equivalent at Screening&#xD;
&#xD;
         15. Parenteral corticosteroids use within 4 weeks of Screening&#xD;
&#xD;
         16. Treatment with cyclosporine (oral or IV), tacrolimus hydrate (excluding eyedrops or&#xD;
             skin cream), sirolimus, or mycophenolate mofetil within 8 weeks before Screening&#xD;
&#xD;
         17. Positive Clostridium difficile toxin test at Screening&#xD;
&#xD;
         18. Known to be human immunodeficiency virus (HIV) positive at Screening&#xD;
&#xD;
         19. History of tuberculosis or known current active tuberculosis&#xD;
&#xD;
         20. Positive results for Mycobacterium tuberculosis using an Interferon-Gamma Release&#xD;
             Assay at Screening&#xD;
&#xD;
         21. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening&#xD;
&#xD;
         22. Use of live vaccine and immunoglobulin preparations within 12 weeks of screening&#xD;
&#xD;
         23. Cluster of differentiation-4 (CD4) positive cell count below 200/microliter (uL) or&#xD;
             white blood cell count below 3,000/uL at screening&#xD;
&#xD;
         24. Any of the following laboratory abnormalities in tests conducted during Screening&#xD;
&#xD;
               -  Hemoglobin: less than 8.0 g/dL&#xD;
&#xD;
               -  Neutrophil count: less than 1,500/uL&#xD;
&#xD;
               -  Platelet count: less than 100,000/uL&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT): greater than&#xD;
                  2.5 times the upper limit of standard reference values&#xD;
&#xD;
               -  Serum creatinine: greater than 1.5 mg/dL&#xD;
&#xD;
         25. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of&#xD;
             antipsychotics or prior suicide attempt(s) within approximately the last 2 years&#xD;
&#xD;
         26. History of drug or alcohol dependency or abuse within the 2 years prior to Screening&#xD;
&#xD;
         27. Current use of illegal recreational drugs&#xD;
&#xD;
         28. Currently enrolled in another clinical study or used any investigational drug or&#xD;
             device within 28 days preceding informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>November 4, 2015</last_update_submitted>
  <last_update_submitted_qc>November 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 5, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crohn's Disease</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>Quetmolimab</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/NCT02249078
org study id: E6011-A001-102
nct id: NCT02249078
lead sponsor: 
has dmc: No
This is a multicenter, Phase 1b, randomized, double-blind, placebo-controlled,
      sequential-cohort, multiple ascending dose (MAD) study to evaluate the safety, tolerability,
      pharmacokinetics (PK), and pharmacodynamics (PD) of 3 subcutaneous and 1 intravenous dose of
      E6011 in subjects with active Crohn's disease (CD). Thirty-two subjects will be randomized to
      one of 4 dose cohorts (8 per cohort) and will receive E6011 or placebo for 10 weeks. The
      first 3 cohorts will receive E6011 or placebo via subcutaneous injection and the last cohort
      will receive E6011 or placebo by intravenous injection. The ratio of E6011 to placebo within
      each cohort will be 3:1. The study has 2 phases: Prerandomization and Randomization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of the short-term safety and tolerability of E6011
time frame: Up to 3 years
description: The short-term safety and tolerability of subcutaneous (SC) and intravenous (IV) doses of E6011 compared to placebo in subjects with active CD. Safety assessments will consist of monitoring and recording all AEs and SAEs; regulatory monitoring of hematology, blood chemistry, and urine values; periodic measurement vital signs and ECGs; and performance of physical examinations.
measure: Concentration of E6011 measured over time in blood samples.
time frame: Up to 3 years
measure: The number and percentage of participants with anti-E6011 antibodies detected in blood samples over time.
time frame: Up to 3 years
measure: The number of screen positives, confirm positives, and relative anti-E6011 levels measured in blood samples from participants.
time frame: Up to 3 years
measure: Change from baseline in the percentage of immunohistochemical staining for the CX3CR1+ protein in intestinal tissue over time.
time frame: Up to 3 years
arm group label: Cohort 1
arm group type: Experimental
description: 100 mg subcutaneous once every 2 weeks with initial double dose (200 mg total)
arm group label: Cohort 2
arm group type: Experimental
description: 200 mg subcutaneous once every 2 weeks with initial double dose (400 mg total)
arm group label: Cohort 3
arm group type: Experimental
description: 400 mg subcutaneous once every 2 weeks with initial double dose (800 mg total)
arm group label: Cohort 4
arm group type: Experimental
description: 10 mg/kg IV at Day 1, Day 8, Day 15, and every 2 weeks thereafter
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo 2-mL vial solution for injection
intervention type: Drug
intervention name: E6011
description: E6011 solution for injection
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
intervention type: Drug
intervention name: Placebo
description: Placebo 2-mL vial solution for injection
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Crohn Disease
mesh term: Quetmolimab