<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/NCT03286582</url>
  </required_header>
  <id_info>
    <org_study_id>AC-203-BP-001</org_study_id>
    <nct_id>NCT03286582</nct_id>
  </id_info>
  <brief_title>A Proof-of-Concept Study of Topical AC-203 in Patients With Bullous Pemphigoid</brief_title>
  <official_title>A Randomized, Open-Label, Controlled Trial of Topical AC-203 in Subjects With Bullous Pemphigoid</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TWi Biotechnology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TWi Biotechnology, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bullous pemphigoid (BP) is a chronic, inflammatory, subepidermal, autoimmune blistering&#xD;
      disease which mainly develops in the elderly, with onset usually in the late 70s and a&#xD;
      substantial increase in incidence in people older than 80 years. If untreated, it can persist&#xD;
      for months or years, with periods of spontaneous remissions and exacerbations. It has been&#xD;
      found that blisters and sera of BP patients contain abnormally high levels of&#xD;
      pro-inflammatory cytokines such as interleukin-6 (IL-6) and IL-8. Recently, it also has been&#xD;
      demonstrated that NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome&#xD;
      components (the NLRP3-caspase-1-IL-18 axis) were significantly up-regulated in peripheral&#xD;
      blood mononuclear cells from BP patients and positively correlated with disease activity.&#xD;
      AC-203 is a topical formulation of an oral modulator of inflammasome and IL-1beta pathways.&#xD;
      In vitro studies have demonstrated that AC-203 significantly reduced secretion of IL-6 and&#xD;
      moderately reduced IL-8 secretion in HaCaT cells treated with specific anti-BP180 IgG. This&#xD;
      study is designed to test the safety, tolerability, efficacy, and pharmacokinetics of AC-203&#xD;
      ointment (vs. a topical steroid comparator representing standard of care) ointment in&#xD;
      subjects with BP.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated with partial enrollment completed&#xD;
  </why_stopped>
  <start_date type="Actual">September 5, 2017</start_date>
  <completion_date type="Actual">January 22, 2019</completion_date>
  <primary_completion_date type="Actual">December 25, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events during the treatment period</measure>
    <time_frame>10 Weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion achieving disease control (no new blisters within prior week)</measure>
    <time_frame>2, 4, 5, 6, 8, 10 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New blister count</measure>
    <time_frame>2, 4, 5, 6, 8, 10 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to disease control</measure>
    <time_frame>2, 4, 5, 6, 8, 10 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who require rescue therapy prior to Week 6</measure>
    <time_frame>2, 4, 5, 6 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BPDAI (BP Disease Area Index) score</measure>
    <time_frame>2, 4, 5, 6, 8, 10 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pruritus VAS (Visual Analogue Scale) score change from baseline</measure>
    <time_frame>2, 4, 5, 6, 8, 10 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLQI (Dermatology Life Quality Index) score change from baseline</measure>
    <time_frame>6, 10 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation marker</measure>
    <time_frame>6 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Bullous Pemphigoid</condition>
  <arm_group>
    <arm_group_label>AC-203</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Clobetasol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AC-203 1% Topical Ointment</intervention_name>
    <description>AC-203 1% ointment BID (twice daily)</description>
    <arm_group_label>AC-203</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clobetasol 0.05% Topical Ointment</intervention_name>
    <description>Clobetasol 0.05% Topical Ointment BID</description>
    <arm_group_label>Clobetasol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 20 to 90 years old, inclusive, at enrollment.&#xD;
&#xD;
          2. Diagnosis of bullous pemphigoid confirmed by histopathology and one of following&#xD;
             assessments:&#xD;
&#xD;
               1. Direct immunoﬂuorescence (DIF)&#xD;
&#xD;
               2. Indirect immunoﬂuorescence (IIF)&#xD;
&#xD;
               3. ELISA test (ELISA detection of immunoglobulin G (IgG) anti-BP180 autoantibodies&#xD;
                  in serum more than 9 U/mL).&#xD;
&#xD;
          3. Localized or limited BP with the occurrence of &lt;10 new blisters per day in the week&#xD;
             prior to enrollment.&#xD;
&#xD;
          4. Is male, or is female and meets all the following criteria:&#xD;
&#xD;
               1. Not breastfeeding&#xD;
&#xD;
               2. If of childbearing potential (defined as non-post hysterectomy or&#xD;
                  non-post-menopausal [≥50 years of age and amenorrheic for at least 1 year]), must&#xD;
                  have a negative pregnancy test result (human chorionic gonadotropin, beta subunit&#xD;
                  [bhCG]) at Visit 1, and must practice and be willing to continue to practice&#xD;
                  appropriate birth control (abstinence, double barrier methods, hormonal&#xD;
                  contraceptives, intrauterine device, or tubal ligation) during the entire&#xD;
                  duration of the study&#xD;
&#xD;
          5. Is able to understand and sign the Informed Consent Form (ICF), communicate with the&#xD;
             investigator, and understand and comply with protocol requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of pemphigus, dermatitis, eczema, psoriasis, or other skin condition which&#xD;
             in the opinion of the investigator may confound diagnosis, treatment, or evaluation of&#xD;
             bullous pemphigoid.&#xD;
&#xD;
          2. Use of oral steroids in the 2 weeks prior to enrollment at a dose greater than&#xD;
             prednisolone equivalent dose (PED) of 10 mg/day.&#xD;
&#xD;
          3. Use of topical steroids for more than 3 consecutive days in the 2 weeks prior to&#xD;
             enrollment.&#xD;
&#xD;
          4. Use of non-steroid immunosuppressants including but not limited to azathioprine,&#xD;
             mycophenolate, cyclophosphamide, chlorambucil, methotrexate, tacrolimus, or&#xD;
             cyclosporine in the 2 weeks prior to enrollment.&#xD;
&#xD;
          5. Use of systemic antibiotics in the 2 weeks prior to enrollment.&#xD;
&#xD;
          6. Use of oral dapsone in the 2 weeks prior to enrollment.&#xD;
&#xD;
          7. Treatment with intravenous immunoglobulin (IVIG) in the 8 weeks prior to enrollment.&#xD;
&#xD;
          8. Any prior use of approved or investigational biologic anti-inflammatory therapy within&#xD;
             6 months prior to enrollment, including but not limited to: anakinra, rilonacept,&#xD;
             canakinumab, etanercept, adalimumab, infliximab, rituximab, certolizumab, golimumab,&#xD;
             tocilizumab, bertilimumab, or abatacept.&#xD;
&#xD;
          9. Presence of active systemic infections.&#xD;
&#xD;
         10. Any clinically significant medical condition or laboratory value that could&#xD;
             potentially affect study participation and/or personal well-being, as judged by the&#xD;
             investigator.&#xD;
&#xD;
         11. History of allergy or hypersensitivity to any component of study medication or&#xD;
             clobetasol.&#xD;
&#xD;
         12. Has participated in a clinical study within 30 days prior to enrollment.&#xD;
&#xD;
         13. Is an immediate family member (spouse, parent, child, or sibling; biological or&#xD;
             legally adopted) of personnel directly affiliated with the study at the clinical study&#xD;
             site, or is directly affiliated with the study at the clinical study site.&#xD;
&#xD;
         14. Is employed by the sponsor (i.e., is an employee, temporary contract worker, or&#xD;
             designee responsible for the conduct of the study).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>September 17, 2019</last_update_submitted>
  <last_update_submitted_qc>September 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pemphigoid, Bullous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clobetasol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03286582
org study id: AC-203-BP-001
nct id: NCT03286582
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Bullous pemphigoid (BP) is a chronic, inflammatory, subepidermal, autoimmune blistering
      disease which mainly develops in the elderly, with onset usually in the late 70s and a
      substantial increase in incidence in people older than 80 years. If untreated, it can persist
      for months or years, with periods of spontaneous remissions and exacerbations. It has been
      found that blisters and sera of BP patients contain abnormally high levels of
      pro-inflammatory cytokines such as interleukin-6 (IL-6) and IL-8. Recently, it also has been
      demonstrated that NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome
      components (the NLRP3-caspase-1-IL-18 axis) were significantly up-regulated in peripheral
      blood mononuclear cells from BP patients and positively correlated with disease activity.
      AC-203 is a topical formulation of an oral modulator of inflammasome and IL-1beta pathways.
      In vitro studies have demonstrated that AC-203 significantly reduced secretion of IL-6 and
      moderately reduced IL-8 secretion in HaCaT cells treated with specific anti-BP180 IgG. This
      study is designed to test the safety, tolerability, efficacy, and pharmacokinetics of AC-203
      ointment (vs. a topical steroid comparator representing standard of care) ointment in
      subjects with BP.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events during the treatment period
time frame: 10 Weeks
measure: Proportion achieving disease control (no new blisters within prior week)
time frame: 2, 4, 5, 6, 8, 10 Weeks
measure: New blister count
time frame: 2, 4, 5, 6, 8, 10 Weeks
measure: Time to disease control
time frame: 2, 4, 5, 6, 8, 10 Weeks
measure: Proportion of subjects who require rescue therapy prior to Week 6
time frame: 2, 4, 5, 6 Weeks
measure: BPDAI (BP Disease Area Index) score
time frame: 2, 4, 5, 6, 8, 10 Weeks
measure: Pruritus VAS (Visual Analogue Scale) score change from baseline
time frame: 2, 4, 5, 6, 8, 10 Weeks
measure: DLQI (Dermatology Life Quality Index) score change from baseline
time frame: 6, 10 Weeks
measure: Inflammation marker
time frame: 6 Weeks
arm group label: AC-203
arm group type: Experimental
arm group label: Clobetasol
arm group type: Active Comparator
intervention type: Drug
intervention name: AC-203 1% Topical Ointment
description: AC-203 1% ointment BID (twice daily)
arm group label: AC-203
intervention type: Drug
intervention name: Clobetasol 0.05% Topical Ointment
description: Clobetasol 0.05% Topical Ointment BID
arm group label: Clobetasol
criteria: 
gender: All
minimum age: 20 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Pemphigoid, Bullous
mesh term: Clobetasol
sharing ipd: No