<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/NCT04422912</url>
  </required_header>
  <id_info>
    <org_study_id>CAB-101</org_study_id>
    <nct_id>NCT04422912</nct_id>
  </id_info>
  <brief_title>Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV)</brief_title>
  <official_title>A Phase 1, Open-label, Safety and Dosing Study of Autologous Desmoglein 3 Chimeric Autoantibody Receptor T Cells (DSG3-CAART) in Subjects With Active, Anti-DSG3, Mucosal-dominant Pemphigus Vulgaris</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cabaletta Bio</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cabaletta Bio</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mucosal-dominant pemphigus vulgaris (mPV) is a B-cell mediated autoimmune disorder in which&#xD;
      painful blisters are formed on the mucosal membrane, including the mouth, nose, throat,&#xD;
      eyelids, anus, and genitals. This phase 1 study is being conducted to find the maximum&#xD;
      tolerated dose and optimal fractionated infusion schedule of an investigational cell therapy,&#xD;
      DSG3-CAART, that can be given to patients with mPV who are inadequately managed by standard&#xD;
      therapies. DSG3-CAART may potentially lead to complete and durable remission of disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 29, 2020</start_date>
  <completion_date type="Anticipated">September 2026</completion_date>
  <primary_completion_date type="Anticipated">September 2026</primary_completion_date>
  <phase>Phase 1</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>Adverse events, including Dose Limit Toxicity</measure>
    <time_frame>3 months</time_frame>
    <description>The primary endpoint of the study is the incidence of adverse events that are related to DSG3-CAART therapy within 3 months of DSG3-CAART cell infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of CAAR-transduced cells</measure>
    <time_frame>Baseline</time_frame>
    <description>Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total DSG3-CAART positive cells</measure>
    <time_frame>Baseline</time_frame>
    <description>Total DSG3-CAART positive cells for each manufacturing run by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cellular kinetics profile of DSG3-CAART</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in DSG3 autoantibody titer</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serologic remission</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pemphigus Disease Area Index (PDAI)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Change in PDAI compared to pre-infusion visit, scored on a 0-250 scale where a greater number represents more disease activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical remission: complete remission off therapy and complete remission on minimal therapy</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Proportion of subjects achieving complete remission, determined by a PDAI activity score of 0 for at least 2 months, either off therapy or on minimal therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to clinical remission and time to serologic remission</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Time to clinical remission and time to serologic remission from the last infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of clinical remission and duration of serologic remission</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">39</enrollment>
  <condition>Mucosal -Dominant Pemphigus Vulgaris</condition>
  <arm_group>
    <arm_group_label>DSG3-CAART</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort A: Fractionated infusions of DSG3-CAART at increasing dose levels (6-9 groups) administered as a single cycle.&#xD;
Cohort B: Consolidation of infusion of DSG3-CAART to fewer fractionations than in Cohort A using the selected dose from Cohort A (1 group) administered as a single cycle.&#xD;
Cohort C: Infusion of final selected dose and fractionation of DSG3-CAART from Cohorts A and B (1 group) administered as a single cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DSG3-CAART</intervention_name>
    <description>Intravenous infusions of DSG3-CAART alone at different doses and different fractionations. Subjects may also receive varying doses of DSG3-CAART as part of a sub-study, which will employ pre-treatment with intravenous immunoglobulin, cyclophosphamide, and with or without fludarabine to potentially increase the in vivo expansion, persistence and activity of DSG3-CAART.</description>
    <arm_group_label>DSG3-CAART</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of mPV by prior or screening biopsy and prior positive anti- DSG3&#xD;
             antibody ELISA&#xD;
&#xD;
          -  mPV inadequately managed by at least one standard immunosuppressive therapies&#xD;
&#xD;
          -  Active mPV at screening&#xD;
&#xD;
          -  Anti-DSG3 antibody ELISA positive at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active cutaneous lesions associated with PV that indicates mucocutaneous rather than&#xD;
             mucosal-dominant disease&#xD;
&#xD;
          -  Rituximab in last 12 months unless PV symptoms have recently worsened or anti-DSG3&#xD;
             antibody titers have recently increased&#xD;
&#xD;
          -  Prednisone &gt; 0.25mg/kg/day&#xD;
&#xD;
          -  Other autoimmune disorder requiring immunosuppressive therapies&#xD;
&#xD;
          -  Investigational treatment in last 6 months&#xD;
&#xD;
          -  Absolute lymphocyte count &lt; 1,000/µL at 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>Cabaletta Bio</last_name>
    <role>Study Chair</role>
    <affiliation>Cabaletta Bio</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Cabaletta Bio</last_name>
    <phone>+1 267 759 3100</phone>
    <email>clinicaltrials@cabalettabio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stanford University, Dept. of Dermatology</name>
      <address>
        <city>Redwood City</city>
        <state>California</state>
        <zip>94063</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isin Sinem Bagci, MD</last_name>
      <phone>650-724-8829</phone>
      <email>isbagci@stanford.edu</email>
    </contact>
    <contact_backup>
      <last_name>Kunju Sridhar, PhD</last_name>
      <phone>650 721 4902</phone>
      <email>kunju@stanford.edu</email>
    </contact_backup>
    <investigator>
      <last_name>M. Peter Marinkovich, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UC Davis, Dept. of Dermatology</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lauren Downing</last_name>
      <phone>916-551-2635</phone>
      <email>ladowning@ucdavis.edu</email>
    </contact>
    <investigator>
      <last_name>Mehrdad Abedi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>NU Dermatology CTU</last_name>
      <phone>312-503-5944</phone>
      <email>NUderm-research@northwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Alan Zhou, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amanda Steahr</last_name>
      <phone>319-384-6843</phone>
      <email>amanda-steahr@uiowa.edu</email>
    </contact>
    <investigator>
      <last_name>Janet Fairley, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mount Sinai - Icahn School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan Lagdameo</last_name>
      <phone>212-241-8552</phone>
      <email>jonathan.lagdameo@mssm.edu</email>
    </contact>
    <contact_backup>
      <last_name>Giselle Singer</last_name>
      <phone>212-241-3288</phone>
      <email>giselle.singer@mssm.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Keren Osman, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of North Carolina, Department of Dermatology</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27516</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suzy Caballero</last_name>
      <phone>984-974-3682</phone>
      <email>nieves_caballero@med.unc.edu</email>
    </contact>
    <investigator>
      <last_name>Donna A Culton, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua Bryer, BA, CCRC</last_name>
      <phone>267-251-6819</phone>
      <email>jbryer@pennmedicine.upenn.edu</email>
    </contact>
    <investigator>
      <last_name>David Porter, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center, Dept. of Dermatology</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aleuna Lee</last_name>
      <phone>214-645-8968</phone>
      <email>aleuna.lee@utsouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Arturo Dominguez, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MD Anderson Texas Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dermatology Department</last_name>
    </contact>
    <investigator>
      <last_name>Omar Pacha, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan Ra</last_name>
      <phone>206-667-5310</phone>
      <email>sra@fredhutch.org</email>
    </contact>
    <investigator>
      <last_name>Michi Shinohara, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pemphigus</keyword>
  <keyword>Pemphigus Vulgaris</keyword>
  <keyword>CAAR-T Therapy</keyword>
  <keyword>CAR-T Therapy</keyword>
  <keyword>Desmoglein 3</keyword>
  <keyword>Cell Therapy</keyword>
  <keyword>Autoimmune Disease</keyword>
  <keyword>Autoimmunity</keyword>
  <keyword>Skin Diseases, Vesiculobullous</keyword>
  <keyword>Immunotherapy, Adoptive</keyword>
  <keyword>Immune System Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pemphigus</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/NCT04422912
org study id: CAB-101
nct id: NCT04422912
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Mucosal-dominant pemphigus vulgaris (mPV) is a B-cell mediated autoimmune disorder in which
      painful blisters are formed on the mucosal membrane, including the mouth, nose, throat,
      eyelids, anus, and genitals. This phase 1 study is being conducted to find the maximum
      tolerated dose and optimal fractionated infusion schedule of an investigational cell therapy,
      DSG3-CAART, that can be given to patients with mPV who are inadequately managed by standard
      therapies. DSG3-CAART may potentially lead to complete and durable remission of disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events, including Dose Limit Toxicity
time frame: 3 months
description: The primary endpoint of the study is the incidence of adverse events that are related to DSG3-CAART therapy within 3 months of DSG3-CAART cell infusion.
measure: Percent of CAAR-transduced cells
time frame: Baseline
description: Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry
measure: Total DSG3-CAART positive cells
time frame: Baseline
description: Total DSG3-CAART positive cells for each manufacturing run by flow cytometry
measure: Cellular kinetics profile of DSG3-CAART
time frame: Up to 36 months
description: Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction
measure: Change in DSG3 autoantibody titer
time frame: Up to 36 months
description: Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit
measure: Serologic remission
time frame: Up to 36 months
description: Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer
measure: Pemphigus Disease Area Index (PDAI)
time frame: Up to 36 months
description: Change in PDAI compared to pre-infusion visit, scored on a 0-250 scale where a greater number represents more disease activity
measure: Clinical remission: complete remission off therapy and complete remission on minimal therapy
time frame: Up to 36 months
description: Proportion of subjects achieving complete remission, determined by a PDAI activity score of 0 for at least 2 months, either off therapy or on minimal therapy
measure: Time to clinical remission and time to serologic remission
time frame: up to 36 months
description: Time to clinical remission and time to serologic remission from the last infusion
measure: Duration of clinical remission and duration of serologic remission
time frame: up to 36 months
description: Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission
arm group label: DSG3-CAART
arm group type: Experimental
description: Cohort A: Fractionated infusions of DSG3-CAART at increasing dose levels (6-9 groups) administered as a single cycle.
Cohort B: Consolidation of infusion of DSG3-CAART to fewer fractionations than in Cohort A using the selected dose from Cohort A (1 group) administered as a single cycle.
Cohort C: Infusion of final selected dose and fractionation of DSG3-CAART from Cohorts A and B (1 group) administered as a single cycle
intervention type: Biological
intervention name: DSG3-CAART
description: Intravenous infusions of DSG3-CAART alone at different doses and different fractionations. Subjects may also receive varying doses of DSG3-CAART as part of a sub-study, which will employ pre-treatment with intravenous immunoglobulin, cyclophosphamide, and with or without fludarabine to potentially increase the in vivo expansion, persistence and activity of DSG3-CAART.
arm group label: DSG3-CAART
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cabaletta Bio
role: Study Chair
affiliation: Cabaletta Bio
last name: Cabaletta Bio
phone: +1 267 759 3100
email: clinicaltrials@cabalettabio.com
facility: 
status: Recruiting
contact: 
contact backup: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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country: United States
responsible party type: Sponsor
mesh term: Pemphigus