<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/NCT01671956</url>
  </required_header>
  <id_info>
    <org_study_id>Immune/BRT/UC-01</org_study_id>
    <nct_id>NCT01671956</nct_id>
  </id_info>
  <brief_title>Evaluation of Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study Designed to Evaluate the Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Profile of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Immune Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Immune Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double blind, placebo-controlled, parallel group multi-center study in&#xD;
      adult patients with active moderate to severe UC . Eligible patients will be randomly&#xD;
      assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching&#xD;
      placebo, respectively&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double blind, placebo-controlled, parallel group multi-center study in&#xD;
      adult patients with active moderate to severe UC . Eligible patients will be randomly&#xD;
      assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching&#xD;
      placebo, respectively.&#xD;
&#xD;
      The study will consist of three periods: a screening period of up to two weeks, a 4-week&#xD;
      double-blind treatment period (three IV infusions at 2-week intervals), and a safety and&#xD;
      efficacy follow-up period of approximately 9 weeks.&#xD;
&#xD;
      Bertilimumab is a recombinant human IgG4 monoclonal antibody that neutralizes human eotaxin-1&#xD;
      (eotaxin). Bertilimumab will be administered every other week for 4-weeks, by IV infusion&#xD;
      over 30 minutes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2015</start_date>
  <completion_date type="Anticipated">March 2019</completion_date>
  <primary_completion_date type="Anticipated">August 2018</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical response</measure>
    <time_frame>Day 56</time_frame>
    <description>A decrease in Mayo score from baseline of at least 3 points and at least 30% AND&#xD;
Either a decrease in the sub-score for rectal bleeding of at least 1 point, or rectal bleeding sub-score of 0 or 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in UCEIS score from screening to Day 56</measure>
    <time_frame>Da 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical remission at Day 56, defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point</measure>
    <time_frame>Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucosal healing at Day 56, defined as an absolute sub-score for endoscopy of 0 or 1.</measure>
    <time_frame>Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in partial Mayo score from Day 0 to all scheduled measurement timepoints (efficacy follow up).</measure>
    <time_frame>Throughout the study</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>PHARMACOKINETICS</measure>
    <time_frame>Throughout the study</time_frame>
    <description>PK analysis for bertilimumab concentration: blood samples will be collected on dosing days (pre-dose and at 30 minutes and 4 hours following initiation of study drug infusion) and at the follow-up visits. The following PK parameters will be calculated, to the degree possible given the number of timepoints: Cmax, Tmax, Cavg, Cmin and t1/2. Additional standard and exploratory PK parameters will be calculated if deemed necessary</description>
  </other_outcome>
  <other_outcome>
    <measure>PHARMACODYNAMIC</measure>
    <time_frame>Throughout the study</time_frame>
    <description>Fecal calprotectin change from Day 0 (baseline) to all scheduled measurement timepoints.&#xD;
PD analysis of eosinophil shape change: blood samples will be collected on dosing days (pre-dose and on Day 0 only, at 4 hours following initiation of study drug infusion), and at the follow-up visits.&#xD;
Change in eosinophil count, serum eotaxin-1 and hs-CRP from Day 0 to all scheduled measurement timepoints.&#xD;
Change in eotaxin-1 concentration and eosinophil count in biopsy tissue from Screening to Day 56</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety</measure>
    <time_frame>Throughout the study</time_frame>
    <description>Adverse events (AE)&#xD;
Injection site reactions&#xD;
Physical examination&#xD;
Vital signs (blood pressure, heart rate, temperature and respiratory rate)&#xD;
ECG&#xD;
Concomitant medications&#xD;
Laboratory evaluation (hematology, biochemistry, anti-bertilimumab antibodies).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Ulcerative Colitis, Active Moderate</condition>
  <condition>Ulcerative Colitis, Active Severe</condition>
  <arm_group>
    <arm_group_label>Bertilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bertilimumab</intervention_name>
    <description>IV infusion over 30 minutes, at Day 0, Day 14 and Day 28</description>
    <arm_group_label>Bertilimumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>IV infusion over 30 minutes, at Day 0, Day 14 and Day 28</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females, 18 to 70 years of age inclusive.&#xD;
&#xD;
          2. Diagnosed with active moderate to severe UC per standard diagnostic criteria for a&#xD;
             minimum of 3 months:&#xD;
&#xD;
               -  Mayo score of 6-12 (inclusive) at the Screening Visit&#xD;
&#xD;
               -  Endoscopic evidence of active mucosal disease, as assessed by flexible&#xD;
                  sigmoidoscopy, with an Endoscopic Finding Sub-score of ≥2 (assessed centrally)&#xD;
&#xD;
               -  Rectal Bleeding Sub-score of ≥1&#xD;
&#xD;
               -  Physician's Global Assessment (PGA) Sub-score of ≥2.&#xD;
&#xD;
          3. Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein.&#xD;
&#xD;
          4. Adequate cardiac, renal and hepatic function as determined by the Investigator and&#xD;
             demonstrated by screening laboratory evaluations and physical examination results;&#xD;
             these findings must all be within normal limits or judged not clinically significant&#xD;
             by the Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy.&#xD;
&#xD;
          2. Currently receiving total parenteral nutrition (TPN).&#xD;
&#xD;
          3. Positive Clostridium difficile toxin stool assay.&#xD;
&#xD;
          4. Tested positive for active/latent mycobacterium tuberculosis (TB) infection.&#xD;
&#xD;
          5. Pregnant or breast-feeding, or plan to become pregnant during the study.&#xD;
&#xD;
          6. Males who are young and childless or planning to have more children in the future.&#xD;
&#xD;
          7. Known hypersensitivity to bertilimumab or any of the drug excipients.&#xD;
&#xD;
          8. History of infection requiring administration of any IV antibiotic, antiviral or&#xD;
             antifungal medication within 30 days of Screening or any oral anti-infective agent&#xD;
             within 14 days of Screening.&#xD;
&#xD;
          9. Severe UC evidenced by the following signs of toxicity: heart rate &gt;100 beats/min at&#xD;
             rest, temperature &gt;37.8°C, hemoglobin &lt;10.0 g/dL.&#xD;
&#xD;
         10. Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal&#xD;
             verge.&#xD;
&#xD;
         11. Received a vaccine or other immunostimulator within 4 weeks prior to screening.&#xD;
&#xD;
         12. Use of &gt;4.8 g mesalazine or equivalent within 2 weeks prior to the screening visit.&#xD;
             Mesalazine ≤4.8 g is allowed if the dose during the 2 weeks prior to the screening&#xD;
             visit was stable.&#xD;
&#xD;
         13. Use of systemic corticosteroids exceeding the equivalent of 20 mg/day of prednisone&#xD;
             within four weeks prior to the screening visit (see Section 6.9.1).&#xD;
&#xD;
         14. Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine&#xD;
             [6-MP], azathioprine) within four weeks prior to the screening visit.&#xD;
&#xD;
         15. Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening&#xD;
             visit.&#xD;
&#xD;
         16. Use of chronic non-steroidal anti-inflammatory (NSAID) therapy. Occasional use of&#xD;
             NSAIDs or acetaminophen for headache, arthritis, myalgias, menstrual cramps, etc., or&#xD;
             daily use of low dose (81-162 mg) aspirin for cardiovascular prophylaxis is allowed.&#xD;
&#xD;
         17. Patients diagnosed with:&#xD;
&#xD;
               -  Crohn's disease&#xD;
&#xD;
               -  Diverticulitis or diverticulosis&#xD;
&#xD;
               -  Indeterminate colitis (inability to distinguish between UC and Crohn's disease&#xD;
                  [as assessed by the Investigator])&#xD;
&#xD;
               -  Microscopic colitis (collagenous or lymphocytic colitis)&#xD;
&#xD;
               -  Ischemic or infectious colitis&#xD;
&#xD;
               -  Clostridium difficile colitis within 90 days of the screening visit&#xD;
&#xD;
               -  Parasitic disease within 90 days of the screening visit&#xD;
&#xD;
               -  Systemic fungal infection within 90 days of the screening visit.&#xD;
&#xD;
         18. History of positive serology of hepatitis B or C, or human immunodeficiency virus&#xD;
             (HIV) infection.&#xD;
&#xD;
         19. Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ&#xD;
             transplantation).&#xD;
&#xD;
         20. Clinically significant abnormal laboratory test results, unless regarded by the&#xD;
             Investigator as related to UC, including but not limited to:&#xD;
&#xD;
               -  Hemoglobin level &lt;10.0 g/dL&#xD;
&#xD;
               -  White blood cell count &lt; 3 x 103/µL&#xD;
&#xD;
               -  Lymphocyte count &lt; 0.5 x 103/µL&#xD;
&#xD;
               -  Platelet count &lt;100 x 103/µL or &gt;1200 x 103/µL&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt;3 the upper&#xD;
                  limit of normal (ULN)&#xD;
&#xD;
               -  Alkaline phosphatase &gt;3 ULN&#xD;
&#xD;
               -  Serum creatinine &gt;2 ULN.&#xD;
&#xD;
         21. Active abuse of alcohol or drugs.&#xD;
&#xD;
         22. Known malignancy or history of malignancy that could reduce life expectancy.&#xD;
&#xD;
         23. Any condition, which in the opinion of the Investigator, would place the patient at an&#xD;
             unacceptable risk if participating in the study protocol.&#xD;
&#xD;
         24. Participation in a clinical trial of an investigational (unapproved) product&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dov Wengrower, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shaare Zedek Medical Center, Jerusalem, Israel</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tony Fiorino, MD</last_name>
    <email>tony.fiorino@immunepharma.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Brenda Kolatch</last_name>
    <email>bkolatch@immunepharma.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>HaEmek Medical Center</name>
      <address>
        <city>Afula</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eran Zittan, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Ika Davidov</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Wolfson Medical Center</name>
      <address>
        <city>Holon</city>
        <zip>58100</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yona Avni, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Orit Shevah</last_name>
    </contact_backup>
    <investigator>
      <last_name>Yona Avni, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek Medical Central</name>
      <address>
        <city>Jerusalem</city>
        <zip>91031</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dov Wengrower, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Chava Kaniel</last_name>
    </contact_backup>
    <investigator>
      <last_name>Dov Wengrower, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hadassah Ein Kerem</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eran Israeli, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Galina Gerber</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Meir Medical Center</name>
      <address>
        <city>Kfar-Saba</city>
        <zip>44299</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fred Konikoff, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Lee Graidy</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Sourasky-Ichilov Tel Aviv Medical Center</name>
      <address>
        <city>Tel- Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sigal Fishman, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Liana Shmialov</last_name>
    </contact_backup>
    <investigator>
      <last_name>Sigal Fishman, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>January 3, 2018</last_update_submitted>
  <last_update_submitted_qc>January 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IBD</keyword>
  <keyword>UC</keyword>
  <keyword>Colitis</keyword>
  <keyword>Ulcerative Colitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_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/NCT01671956
org study id: Immune/BRT/UC-01
nct id: NCT01671956
lead sponsor: 
has dmc: No
This is a randomized, double blind, placebo-controlled, parallel group multi-center study in
      adult patients with active moderate to severe UC . Eligible patients will be randomly
      assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching
      placebo, respectively
This is a randomized, double blind, placebo-controlled, parallel group multi-center study in
      adult patients with active moderate to severe UC . Eligible patients will be randomly
      assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching
      placebo, respectively.

      The study will consist of three periods: a screening period of up to two weeks, a 4-week
      double-blind treatment period (three IV infusions at 2-week intervals), and a safety and
      efficacy follow-up period of approximately 9 weeks.

      Bertilimumab is a recombinant human IgG4 monoclonal antibody that neutralizes human eotaxin-1
      (eotaxin). Bertilimumab will be administered every other week for 4-weeks, by IV infusion
      over 30 minutes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Clinical response
time frame: Day 56
description: A decrease in Mayo score from baseline of at least 3 points and at least 30% AND
Either a decrease in the sub-score for rectal bleeding of at least 1 point, or rectal bleeding sub-score of 0 or 1.
measure: Change in UCEIS score from screening to Day 56
time frame: Da 56
measure: Clinical remission at Day 56, defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point
time frame: Day 56
measure: Mucosal healing at Day 56, defined as an absolute sub-score for endoscopy of 0 or 1.
time frame: Day 56
measure: Change in partial Mayo score from Day 0 to all scheduled measurement timepoints (efficacy follow up).
time frame: Throughout the study
measure: PHARMACOKINETICS
time frame: Throughout the study
description: PK analysis for bertilimumab concentration: blood samples will be collected on dosing days (pre-dose and at 30 minutes and 4 hours following initiation of study drug infusion) and at the follow-up visits. The following PK parameters will be calculated, to the degree possible given the number of timepoints: Cmax, Tmax, Cavg, Cmin and t1/2. Additional standard and exploratory PK parameters will be calculated if deemed necessary
measure: PHARMACODYNAMIC
time frame: Throughout the study
description: Fecal calprotectin change from Day 0 (baseline) to all scheduled measurement timepoints.
PD analysis of eosinophil shape change: blood samples will be collected on dosing days (pre-dose and on Day 0 only, at 4 hours following initiation of study drug infusion), and at the follow-up visits.
Change in eosinophil count, serum eotaxin-1 and hs-CRP from Day 0 to all scheduled measurement timepoints.
Change in eotaxin-1 concentration and eosinophil count in biopsy tissue from Screening to Day 56
measure: Safety
time frame: Throughout the study
description: Adverse events (AE)
Injection site reactions
Physical examination
Vital signs (blood pressure, heart rate, temperature and respiratory rate)
ECG
Concomitant medications
Laboratory evaluation (hematology, biochemistry, anti-bertilimumab antibodies).
arm group label: Bertilimumab
arm group type: Experimental
description: Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes
arm group label: Placebo
arm group type: Placebo Comparator
description: Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.
intervention type: Biological
intervention name: Bertilimumab
description: IV infusion over 30 minutes, at Day 0, Day 14 and Day 28
arm group label: Bertilimumab
intervention type: Biological
intervention name: Placebo
description: IV infusion over 30 minutes, at Day 0, Day 14 and Day 28
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Dov Wengrower, MD
role: Principal Investigator
affiliation: Shaare Zedek Medical Center, Jerusalem, Israel
last name: Tony Fiorino, MD
email: tony.fiorino@immunepharma.com
last name: Brenda Kolatch
email: bkolatch@immunepharma.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Israel
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer