<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/NCT02226146</url>
  </required_header>
  <id_info>
    <org_study_id>Immune/BRT/BP-01</org_study_id>
    <nct_id>NCT02226146</nct_id>
  </id_info>
  <brief_title>Evaluation of Safety, Efficacy and Pharmacodynamic Effect of Bertilimumab in Patients With Bullous Pemphigoid</brief_title>
  <official_title>An Open-Label, Proof of Concept Study Designed to Evaluate the Safety, Efficacy and Pharmacodynamic Effect of Bertilimumab in Patients With Newly Diagnosed, Moderate to Extensive Bullous Pemphigoid</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 an open-label, proof-of-concept, single group study in adult patients with newly&#xD;
      diagnosed, moderate to extensive BP.&#xD;
&#xD;
      The study will consist of three periods: a screening period of up to 2 weeks, an open-label&#xD;
      treatment period lasting 4 weeks consisting of IV infusion of bertilimumab on Days 0 and 14&#xD;
      and 28, and a safety and efficacy follow-up period of approximately 13 weeks.&#xD;
&#xD;
      Patients will receive concomitant oral steroids during the treatment and follow-up period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, proof-of-concept, single group study in adult patients with newly&#xD;
      diagnosed, moderate to extensive BP.&#xD;
&#xD;
      The study will consist of three periods: a screening period of up to 2 weeks, an open-label&#xD;
      treatment period lasting 4 weeks consisting of IV infusion of bertilimumab on Days 0 and 14&#xD;
      and Day 28, and a safety and efficacy follow-up period of approximately 13 weeks.&#xD;
&#xD;
      Patients will receive concomitant oral steroids during the treatment and follow-up period.&#xD;
      They will start on 30 mg prednisone daily (or equivalent). The initial dose will be&#xD;
      maintained for at least 1 week, commencing on Day 0, until blister formation has ceased,&#xD;
      crusts and erosions have disappeared and reepithelialization of lesions has started. The&#xD;
      corticosteroid dose will then be reduced to 20 mg daily for 5 to 14 days. According to&#xD;
      clinical response, this will be followed by corticosteroid dose reduction in 5 mg steps every&#xD;
      5 to 14 days until a dose of 10 mg daily is reached and then corticosteroid dose reduction in&#xD;
      2.5 mg steps every 5 to 14 days until the end of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2016</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety Endpoints</measure>
    <time_frame>Participants will be followed for the duration of the study , an expected average of 118 days</time_frame>
    <description>Safety outcome would be assessed as the number of the following events which the participants experienced throughout the study:&#xD;
Number if Adverse events (AE)&#xD;
Injection site reactions after infusions&#xD;
Abnormal Physical findings during the examination&#xD;
Abnormal Vital signs (blood pressure, heart rate, temperature)&#xD;
Abnormal ECG&#xD;
Number of Concomitant medications taken&#xD;
Abnormal Laboratory values&#xD;
Development of anti-bertilimumab antibodies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Change in Bullous Pemphigoid Disease Area Index (BPDAI)</measure>
    <time_frame>Participants will be followed for the duration of the study, an expected average of 84 days</time_frame>
    <description>The BPDAI is a validated measure of bullous pemphigoid disease activity consisting of four subscores: skin blistering (0-120), uricaria (0-120), mucosal blistering (0-120) and damage/pigmentation (0-12). The activity score consists of the first three subscored (0-360)&#xD;
• Change in BPDAI Activity Score at each scheduled measurement timepoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: BPDAI responders</measure>
    <time_frame>Participants will be followed for the duration of the study, an expected average of 84 days</time_frame>
    <description>• Proportion of subjects who achieve a reduction in BPDAI Activity Score of at least 50%, 75% and 90% at Days 42, 56, 70 or 84</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Prednisone dose</measure>
    <time_frame>Participants will be followed for the duration of the study, an expected average of 84 days</time_frame>
    <description>• Proportion of subjects who have tapered to prednisone dose of ≤10 mg/day at at Days 42, 56, 70 or 84</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Change in BPDAI pruritus component</measure>
    <time_frame>Participants will be followed for the duration of the study, an expected average of 84 days</time_frame>
    <description>• Change in pruritus visual analog scale (the sum of three 0-10 pruritus assessments: pruritus intensity over the prior day, week and month) at each scheduled measurement timepoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Change in Autoimmune Bullous Disease Quality of Life (ABQOL)</measure>
    <time_frame>Participants will be followed for the duration of the study, an expected average of 84 days</time_frame>
    <description>The ABQOL questionnaire is a validated 17 item questionnaire (range 0-51) assessing quality of life in patients with autoimmune blistering diseases&#xD;
• ABQOL assessed at each scheduled measurement timepoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Control of disease activity</measure>
    <time_frame>Participants will be followed for the duration of the study, an expected average of 84 days</time_frame>
    <description>Control of disease activity is defined as the time when at least two of the following occur: new lesions cease to form, established lesions begin to heal and/or pruritic symptoms start to abate.&#xD;
• Mean time from baseline to control of disease activity</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic (PK) Endpoints - Cmax</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</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 once at remaining study visits (excluding screening). The following PK parameters will be calculated, to the degree possible given the number of timepoints: Cmax, Tmax, AUC, Vdist and t1/2. Additional standard and exploratory PK parameters will be calculated if deemed necessary. Cmax is the maximum bertilimumab serum concentration observed.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic (PK) Endpoints - Tmax</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• Tmax is the time until Cmax</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic (PK) Endpoints - AUC</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• AUC is the area under the curve</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic (PK) Endpoints - Vdist</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• Vdist is the volume of ditribution</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic (PK) Endpoints - T1/2</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• T1/2 is the elimination half life</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamic Endpoint: Change in autoantibody titres</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• Change in BP180 and BP230 autoantibody titres at each scheduled sampling timepoint compared to baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamic Endpoint: Change in blood eosinophil count</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• Change in blood eosinophil count at each scheduled sampling timepoint compared to baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamic Endpoint: Change in tissue eosinophil count</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• Change in tissue eosinophil count assessed on biopsy at the scheduled timepoint compared to screening</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamic Endpoint: Change in serum eotaxin-1 level</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>• Change in serum eotaxin-1 level at each scheduled sampling timepoint compared to baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Endpoint: Change in biomarkers</measure>
    <time_frame>Participants will be followed the duration of the study, an expected average of 84 days</time_frame>
    <description>Change in PBMC biomarkers at each scheduled timepoint compared to baseline, including but not limited to: CD4, CD25, CD8, CD69, CD62L, CCR3 and Foxp3 via flow cytometry analyses.&#xD;
Change in Eosinophil Cationic Protein serum levels</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Pemphigoid, Bullous</condition>
  <arm_group>
    <arm_group_label>Bertilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous injection over 30 minutes of 10 mg/kg of Bertilimumab in physiological solution (PBS)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bertilimumab</intervention_name>
    <arm_group_label>Bertilimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females, ≥ 60 years of age.&#xD;
&#xD;
          2. Karnofsky performance status &gt; 60%&#xD;
&#xD;
          3. Newly diagnosed, Bullous Pemphigoid per standard diagnostic criteria:&#xD;
&#xD;
               -  Clinical presentation [2]&#xD;
&#xD;
               -  Skin biopsy from a fresh blister showing subepidermal clefting and an&#xD;
                  inflammatory infiltrate consisting mainly of eosinophils&#xD;
&#xD;
               -  Immunofluorescence (IF) studies performed on uninvolved skin collected&#xD;
                  approximately 1 cm away from a fresh blister showing linear deposition of IgG&#xD;
                  and/or C3 along the basement membrane zone.&#xD;
&#xD;
          4. Moderate to extensive Bullous Pemphigoid defined by the mean number of new bullae and&#xD;
             urticarial plaques that have appeared over the course of 3 days as determined by the&#xD;
             investigator or referring physician (moderate disease defined by &gt; 1 and ≤ 10 new&#xD;
             bullae daily and ≥ 5 urticarial plaques and extensive disease by &gt;10 new bullae daily)&#xD;
             [3].&#xD;
&#xD;
          5. Adequate cardiac, renal and hepatic function as determined by the Investigator and&#xD;
             demonstrated by screening laboratory evaluations, vital sign measurement, ECG&#xD;
             recording and physical examination results.&#xD;
&#xD;
          6. Females of childbearing potential must agree to use effective contraception&#xD;
             consistently throughout the study (such as hormonal contraception or two forms of&#xD;
             barrier contraception) and have a negative serum pregnancy test at screening and a&#xD;
             negative urine pregnancy test per the schedule of visits. Women are considered&#xD;
             post-menopausal and not of childbearing potential if they have had 12 months of&#xD;
             amenorrhea or have had surgical bilateral oophorectomy (with or without hysterectomy)&#xD;
             or tubal ligation at least six weeks previously.&#xD;
&#xD;
          7. Males must have had a vasectomy or have expressed that they have no interest in&#xD;
             fertility in the future.&#xD;
&#xD;
          8. Fertile males must agree to use effective contraception consistently throughout the&#xD;
             study and for a period of four months following the end of study drug administration.&#xD;
&#xD;
          9. Willing and able to adhere to the study visit schedule and other protocol&#xD;
             requirements.&#xD;
&#xD;
         10. Willing and able to provide voluntary written informed consent or written informed&#xD;
             consent from a legally authorized representative with assent from the patient.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Patients with severe medical or surgical conditions at screening or baseline&#xD;
             including, but not limited to, severe dementia or mental impairment, severe stroke,&#xD;
             severe cardiac insufficiency, severe arterial hypertension, severe or uncontrolled&#xD;
             renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac,&#xD;
             neurologic, cerebral, psychiatric, or any other severe acute or chronic medical&#xD;
             condition that may increase the risk associated with study participation/treatment or&#xD;
             may interfere with the interpretation of study results and, in the Investigator's&#xD;
             opinion, would make the patient inappropriate for study entry.&#xD;
&#xD;
          2. Presence of any malignancy that has been under active treatment (e.g., radiotherapy or&#xD;
             chemotherapy) within the 2 years prior to baseline or is anticipated to require&#xD;
             treatment during the study period (including follow up) with the exception of patients&#xD;
             with removal of uncomplicated basal cell carcinoma or cutaneous squamous cell&#xD;
             carcinoma, who may take part in the study.&#xD;
&#xD;
          3. Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ&#xD;
             transplantation).&#xD;
&#xD;
          4. Clinically significant vital sign measurements or ECG findings as determined by the&#xD;
             Investigator.&#xD;
&#xD;
          5. Clinically significant abnormal laboratory test results, unless regarded by the&#xD;
             Investigator as related to BP, 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;
          6. Patients with mild, relapsed or refractory Bullous Pemphigoid. Mild disease defined by&#xD;
             the mean number of new lesions that have appeared over the course of 3 days as&#xD;
             determined by the investigator or referring physician, as follows: ≤ 1 bulla or &lt; 5&#xD;
             urticarial plaques.&#xD;
&#xD;
          7. Concomitant skin conditions preventing physical evaluation of Bullous Pemphigoid.&#xD;
&#xD;
          8. Active or recent history of clinically significant infection within 1 month of&#xD;
             baseline.&#xD;
&#xD;
          9. Pregnant or breast-feeding, or planning to become pregnant during the study.&#xD;
&#xD;
         10. Participation in a clinical trial of an investigational (unapproved) product within 4&#xD;
             weeks of baseline.&#xD;
&#xD;
         11. Known hypersensitivity to bertilimumab or any of the drug excipients.&#xD;
&#xD;
         12. Use of prednisone or other systemic steroids (excluding inhaled or ocular use of&#xD;
             steroids) within 4 weeks prior to baseline. (Concomitant oral corticosteroids&#xD;
             administered as part of the study protocol, from Day 0 onward, are allowed). Use of&#xD;
             class 1 and 2 topical steroids (such as clobetasol propionate cream, reference&#xD;
             Appendix D for further guidance) within 4 weeks prior to baseline. (Use of other&#xD;
             topical steroids is allowed throughout the study at the discretion of the&#xD;
             investigator).&#xD;
&#xD;
         13. Treatment with immunosuppressants (e.g., azathioprine, methotrexate) within 4 weeks&#xD;
             prior to baseline.&#xD;
&#xD;
         14. Treatment with biologics (e.g., etanercept, adalimumab, ustekinumab, infliximab,&#xD;
             intravenous Ig) within 4 months of baseline. Patients who have received rituximab&#xD;
             within 1 year of baseline will be excluded from study participation.&#xD;
&#xD;
         15. Treatment with macrolides or tetracyclines within 4 weeks prior to baseline.&#xD;
&#xD;
         16. Received a vaccine or other immunostimulator within 4 weeks prior to baseline. Subject&#xD;
             has current clinical, radiographic or laboratory evidence of active mycobacterium&#xD;
             tuberculosis (TB) infection or prior evidence of active TB that, in the opinion of the&#xD;
             investigator, has not been adequately treated or controlled and that represents a&#xD;
             reactivation risk. If in the investigator's opinion the patient is at risk for latent&#xD;
             TB, the patient should be evaluated for active/latent TB as applicable (e.g. PPD, QFT,&#xD;
             and/or chest x-ray).&#xD;
&#xD;
        18. Evidence of an active disease of hepatitis B (HBsAg positive or HBcAb positive) or&#xD;
        hepatitis C (HCV ab positive), CMV (IgM positive) or human immunodeficiency virus (HIV)&#xD;
        infection (HIV1/2 Ab positive 19. Active abuse of alcohol or drugs. 20. Any other&#xD;
        condition, which in the opinion of the Investigator would place the patient at an&#xD;
        unacceptable risk if participating in the study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eli Sprecher, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sourasky-Ichilov Tel Aviv Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University at Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cleveland</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>10900</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba MC, Tel-Hashomer</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5262100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky-Ichilov Tel Aviv Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>July 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>May 21, 2018</last_update_submitted>
  <last_update_submitted_qc>May 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pemphigoid Bullous</keyword>
  <keyword>Bullous</keyword>
  <keyword>Blisters</keyword>
  <keyword>SKIN DISEASES</keyword>
  <keyword>BP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pemphigoid, Bullous</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/NCT02226146
org study id: Immune/BRT/BP-01
nct id: NCT02226146
lead sponsor: 
has dmc: No
This is an open-label, proof-of-concept, single group study in adult patients with newly
      diagnosed, moderate to extensive BP.

      The study will consist of three periods: a screening period of up to 2 weeks, an open-label
      treatment period lasting 4 weeks consisting of IV infusion of bertilimumab on Days 0 and 14
      and 28, and a safety and efficacy follow-up period of approximately 13 weeks.

      Patients will receive concomitant oral steroids during the treatment and follow-up period.
This is an open-label, proof-of-concept, single group study in adult patients with newly
      diagnosed, moderate to extensive BP.

      The study will consist of three periods: a screening period of up to 2 weeks, an open-label
      treatment period lasting 4 weeks consisting of IV infusion of bertilimumab on Days 0 and 14
      and Day 28, and a safety and efficacy follow-up period of approximately 13 weeks.

      Patients will receive concomitant oral steroids during the treatment and follow-up period.
      They will start on 30 mg prednisone daily (or equivalent). The initial dose will be
      maintained for at least 1 week, commencing on Day 0, until blister formation has ceased,
      crusts and erosions have disappeared and reepithelialization of lesions has started. The
      corticosteroid dose will then be reduced to 20 mg daily for 5 to 14 days. According to
      clinical response, this will be followed by corticosteroid dose reduction in 5 mg steps every
      5 to 14 days until a dose of 10 mg daily is reached and then corticosteroid dose reduction in
      2.5 mg steps every 5 to 14 days until the end of the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety Endpoints
time frame: Participants will be followed for the duration of the study , an expected average of 118 days
description: Safety outcome would be assessed as the number of the following events which the participants experienced throughout the study:
Number if Adverse events (AE)
Injection site reactions after infusions
Abnormal Physical findings during the examination
Abnormal Vital signs (blood pressure, heart rate, temperature)
Abnormal ECG
Number of Concomitant medications taken
Abnormal Laboratory values
Development of anti-bertilimumab antibodies
measure: Efficacy Endpoint: Change in Bullous Pemphigoid Disease Area Index (BPDAI)
time frame: Participants will be followed for the duration of the study, an expected average of 84 days
description: The BPDAI is a validated measure of bullous pemphigoid disease activity consisting of four subscores: skin blistering (0-120), uricaria (0-120), mucosal blistering (0-120) and damage/pigmentation (0-12). The activity score consists of the first three subscored (0-360)
• Change in BPDAI Activity Score at each scheduled measurement timepoint
measure: Efficacy Endpoint: BPDAI responders
time frame: Participants will be followed for the duration of the study, an expected average of 84 days
description: • Proportion of subjects who achieve a reduction in BPDAI Activity Score of at least 50%, 75% and 90% at Days 42, 56, 70 or 84
measure: Efficacy Endpoint: Prednisone dose
time frame: Participants will be followed for the duration of the study, an expected average of 84 days
description: • Proportion of subjects who have tapered to prednisone dose of ≤10 mg/day at at Days 42, 56, 70 or 84
measure: Efficacy Endpoint: Change in BPDAI pruritus component
time frame: Participants will be followed for the duration of the study, an expected average of 84 days
description: • Change in pruritus visual analog scale (the sum of three 0-10 pruritus assessments: pruritus intensity over the prior day, week and month) at each scheduled measurement timepoint
measure: Efficacy Endpoint: Change in Autoimmune Bullous Disease Quality of Life (ABQOL)
time frame: Participants will be followed for the duration of the study, an expected average of 84 days
description: The ABQOL questionnaire is a validated 17 item questionnaire (range 0-51) assessing quality of life in patients with autoimmune blistering diseases
• ABQOL assessed at each scheduled measurement timepoint
measure: Efficacy Endpoint: Control of disease activity
time frame: Participants will be followed for the duration of the study, an expected average of 84 days
description: Control of disease activity is defined as the time when at least two of the following occur: new lesions cease to form, established lesions begin to heal and/or pruritic symptoms start to abate.
• Mean time from baseline to control of disease activity
measure: Pharmacokinetic (PK) Endpoints - Cmax
time frame: Participants will be followed the duration of the study, an expected average of 84 days
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 once at remaining study visits (excluding screening). The following PK parameters will be calculated, to the degree possible given the number of timepoints: Cmax, Tmax, AUC, Vdist and t1/2. Additional standard and exploratory PK parameters will be calculated if deemed necessary. Cmax is the maximum bertilimumab serum concentration observed.
measure: Pharmacokinetic (PK) Endpoints - Tmax
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • Tmax is the time until Cmax
measure: Pharmacokinetic (PK) Endpoints - AUC
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • AUC is the area under the curve
measure: Pharmacokinetic (PK) Endpoints - Vdist
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • Vdist is the volume of ditribution
measure: Pharmacokinetic (PK) Endpoints - T1/2
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • T1/2 is the elimination half life
measure: Pharmacodynamic Endpoint: Change in autoantibody titres
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • Change in BP180 and BP230 autoantibody titres at each scheduled sampling timepoint compared to baseline
measure: Pharmacodynamic Endpoint: Change in blood eosinophil count
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • Change in blood eosinophil count at each scheduled sampling timepoint compared to baseline
measure: Pharmacodynamic Endpoint: Change in tissue eosinophil count
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • Change in tissue eosinophil count assessed on biopsy at the scheduled timepoint compared to screening
measure: Pharmacodynamic Endpoint: Change in serum eotaxin-1 level
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: • Change in serum eotaxin-1 level at each scheduled sampling timepoint compared to baseline
measure: Exploratory Endpoint: Change in biomarkers
time frame: Participants will be followed the duration of the study, an expected average of 84 days
description: Change in PBMC biomarkers at each scheduled timepoint compared to baseline, including but not limited to: CD4, CD25, CD8, CD69, CD62L, CCR3 and Foxp3 via flow cytometry analyses.
Change in Eosinophil Cationic Protein serum levels
arm group label: Bertilimumab
arm group type: Experimental
description: Intravenous injection over 30 minutes of 10 mg/kg of Bertilimumab in physiological solution (PBS)
intervention type: Biological
intervention name: Bertilimumab
arm group label: Bertilimumab
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Eli Sprecher, MD
role: Principal Investigator
affiliation: Sourasky-Ichilov Tel Aviv Medical Center
facility: 
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country: Israel
country: United States
responsible party type: Sponsor
mesh term: Pemphigoid, Bullous