<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/NCT03239470</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT APG01</org_study_id>
    <secondary_id>APG01</secondary_id>
    <secondary_id>NIAID CRMS ID#: 37534</secondary_id>
    <nct_id>NCT03239470</nct_id>
  </id_info>
  <brief_title>Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus</brief_title>
  <official_title>A Phase I, Open-Label, Multicenter Trial Exploring the Safety and Tolerability of Autologous Polyclonal Regulatory T Cell Therapy in Adults With Active Pemphigus (APG01)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Autoimmunity Centers of Excellence</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rho Federal Systems Division, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      T cells, a type of white blood cell called a lymphocyte, play an important role in the immune&#xD;
      system. One subtype, the regulatory T cell (Treg) helps to regulate the immune system and may&#xD;
      provide protection against the development of autoimmune disease. The hope is that these&#xD;
      naturally occurring Treg cells can be utilized for the treatment of autoimmune disease and&#xD;
      potentially replace the use of chronic immunosuppressive therapies that are associated with&#xD;
      multiple side effects. There has been a small study showing safe administration of Tregs with&#xD;
      decreased disease activity in patients with insulin-dependent diabetes. Tregs are being&#xD;
      studied in lupus, cancer and organ transplantation.&#xD;
&#xD;
      This phase I trial will be conducted as an open-label, dose-escalation, multicenter trial in&#xD;
      adult participants with active pemphigus.The purpose of this study is to test the safety and&#xD;
      effect of Treg therapy in participants who have skin (cutaneous) involvement due to&#xD;
      pemphigus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 12 adults between the ages of 18 and 75 years of age who have been diagnosed with&#xD;
      pemphigus and meet all other entry criteria will be enrolled to receive one infusion of their&#xD;
      own expanded Tregs at one of the following doses:&#xD;
&#xD;
        -  1.0 x 10^8 PolyTregs or&#xD;
&#xD;
        -  2.5 x 10^8 PolyTregs.&#xD;
&#xD;
      Safety, disease activity, and mechanism of action will be assessed over a three year period,&#xD;
      using biospecimens from blood and skin. Study therapy administration will occur during an&#xD;
      overnight stay, followed by 2 weekly visits, then monthly visits from Week 8 to Week 12, then&#xD;
      quarterly visits from Week 26 to Week 52, then twice a year visits until Week 156.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of recruitment, ongoing and new feasibility issues, and the impact of the coronavirus&#xD;
    infectious disease 19 (COVID-19) pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">October 10, 2017</start_date>
  <completion_date type="Actual">January 9, 2023</completion_date>
  <primary_completion_date type="Actual">December 10, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Significant Adverse Events Through Week 52</measure>
    <time_frame>Up to Week 52</time_frame>
    <description>Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event (SAE). Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.&#xD;
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Significant Events Through Week 156</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event. Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs*, as determined by the safety review committee.&#xD;
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) Related to Treatment, Polyclonal Tregs Infusion Through Week 52</measure>
    <time_frame>Up to Week 52</time_frame>
    <description>All adverse events (AEs) of specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) as a measure of safety and toxicity of the PolyTregs infusion*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Grade 3 to 5 Adverse Events (AEs) Through Week 52</measure>
    <time_frame>Up to Week 52</time_frame>
    <description>All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Grade 3 to 5 Adverse Events (AEs) Through Week 156</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Serious Adverse Events (SAEs) Through Week 156</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
**Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Infection-Related Adverse Events (AEs) Through Week 156</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>Safety measure. Monitoring for signs and symptoms of infection-related AEs (e.g., viral, bacterial, or fungal organism, particularly opportunistic infections).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Infusion-Related Reactions Within 24 Hours of PolyTregs Infusion</measure>
    <time_frame>Up to 24 hours post infusion</time_frame>
    <description>Any infusion-related adverse events (AEs) Grade 1 or higher that occur within 24 hours of polyclonal Tregs* infusion. This study will grade the severity of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pemphigus Disease Area Index (PDAI)</measure>
    <time_frame>From Baseline (Week 0) to Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156</time_frame>
    <description>Pemphigus Disease Area Index (PDAI) is a cutaneous and mucosal disease activity assessment performed by the investigator, based on evaluation of lesions in well-defined anatomical locations. The score is weighted for the number and size of lesions, with a score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion(s), are scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranges from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Desmoglein (DSG) Autoantibody Titers</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>Desmoglein (DSG) autoantibodies serum levels, measured by ELISA (enzyme-linked immunosorbent assay, compared to pre PolyTregs infusion DSG autoantibody levels*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Initial Flare/Relapse by Week 156</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>Time from initiation of polyTregs infusion* to the the time of the appearance of ≥3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the polyTregs infusion initiation.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants on a Prednisone Dose ≤10 Milligrams Per Day (mg/Day)</measure>
    <time_frame>Up to Week 156</time_frame>
    <description>A measure of efficacy. This will be assessed at Weeks 12, 26, 39, 52, 78, 104, 130, and 156.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Pemphigus Foliaceus</condition>
  <condition>Pemphigus Vulgaris</condition>
  <arm_group>
    <arm_group_label>Cohort 1: 1.0 x 10^8 PolyTregs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single intravenous infusion of 1.0 x 10^8 PolyTregs will be administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: 2.5x10^8 PolyTregs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single intravenous infusion of 2.5x10^8 PolyTregs will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cohort 1: 1.0 x 10^8 PolyTregs</intervention_name>
    <description>Each participant will receive a target cell dose of 1.0 x 10^8 polyclonal Tregs.</description>
    <arm_group_label>Cohort 1: 1.0 x 10^8 PolyTregs</arm_group_label>
    <other_name>Polyclonal Regulatory T Cells</other_name>
    <other_name>autologous PolyTregs</other_name>
    <other_name>CD4+CD127lo/negCD25+ PolyTregs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cohort 2: 2.5x10^8 PolyTregs</intervention_name>
    <description>Each participant will receive a target cell dose of 2.5x10^8 polyclonal Tregs.</description>
    <arm_group_label>Cohort 2: 2.5x10^8 PolyTregs</arm_group_label>
    <other_name>Polyclonal Regulatory T Cells</other_name>
    <other_name>autologous PolyTregs</other_name>
    <other_name>CD4+CD127lo/negCD25+ PolyTregs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide informed consent;&#xD;
&#xD;
          -  Diagnosis of Pemphigus Vulgaris (PV) or Pemphigus Foliaceus (PF), defined by H&amp;E&#xD;
             staining (e.g., Haemotoxylin and Eosin) and direct immunofluorescence staining of skin&#xD;
             biopsy at any time prior to enrollment;&#xD;
&#xD;
          -  Pemphigus treated with systemic corticosteroids within the 2 years prior to screening&#xD;
             (historic or current), or treated with rituximab ≥ 12 months prior to screening;&#xD;
&#xD;
          -  Presence of:&#xD;
&#xD;
               -  anti-Dsg3 antibodies (&gt;20.0 U/ml) at screening visit consistent with diagnosis of&#xD;
                  pemphigus vulgaris or,&#xD;
&#xD;
               -  anti-Dsg1 antibodies (&gt;20.0 U/ml) at screening visit consistent with diagnosis of&#xD;
                  pemphigus foliaceus.&#xD;
&#xD;
          -  Active of PV or PF as defined by Pemphigus Disease Area Index (PDAI) overall activity&#xD;
             score 3-10 at screening visit, and PDAI overall activity score 1-12 at baseline visit;&#xD;
&#xD;
          -  Positive test for Epstein-Barr Virus (EBV) antibody;&#xD;
&#xD;
          -  Adequate venous access to support draw of 400 ml whole blood and infusion of&#xD;
             investigational therapy; and&#xD;
&#xD;
          -  An absolute Treg count of ≥ 42 cells/μL within 6 weeks prior to whole blood collection&#xD;
             at Week -2 (i.e., 2 weeks prior to planned PolyTreg Infusion).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Initiation of systemic corticosteroid therapy, prednisone dose &gt; 25 mg/d (or&#xD;
             equivalent) or change in prednisone dose within 4 weeks prior to screening;&#xD;
&#xD;
          -  Addition of a new medication, or change in the dose of any background medication used&#xD;
             to treat any aspect of pemphigus within the timeframes listed below. Specifically:&#xD;
&#xD;
               -  methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine,&#xD;
                  cyclosporine or dapsone within the 6 weeks prior to screening or in the time&#xD;
                  between screening and study drug infusion,&#xD;
&#xD;
               -  intravenous Immunoglobulin (IVIG) within 12 weeks prior to screening or in the&#xD;
                  time between screening and study drug infusion (subjects on IVIG must be on&#xD;
                  stable dose for at least 12 weeks prior to screening),&#xD;
&#xD;
               -  treatment with cyclophosphamide within 12 weeks prior to screening or in the time&#xD;
                  between screening and study drug infusion.&#xD;
&#xD;
          -  Doses of background medications at screening:&#xD;
&#xD;
               -  methotrexate &gt; 25 mg/week,&#xD;
&#xD;
               -  mycophenolate mofetil &gt; 3000 mg/d,&#xD;
&#xD;
               -  mycophenolic acid &gt; 1080 mg/bid,&#xD;
&#xD;
               -  azathioprine &gt; 200 mg/d,&#xD;
&#xD;
               -  cyclosporine &gt; 2 mg/kg/d,&#xD;
&#xD;
               -  dapsone &gt;250 mg/d,or&#xD;
&#xD;
               -  intravenous immunoglobulin (IVIG) &gt; 4mg/kg monthly.&#xD;
&#xD;
          -  Use of rituximab within the 12 months prior to screening;&#xD;
&#xD;
          -  Change in dosing frequency, concentration, or applied surface area of topical steroids&#xD;
             and/or topical calcineurin inhibitors within 2 weeks prior to screening;&#xD;
&#xD;
          -  Paraneoplastic pemphigus;&#xD;
&#xD;
          -  Pemphigus erythematosus;&#xD;
&#xD;
          -  Pemphigus vegetans;&#xD;
&#xD;
          -  Immunoglobulin A (IgA) pemphigus;&#xD;
&#xD;
          -  Drug-induced pemphigus;&#xD;
&#xD;
          -  Blood donation within 10 weeks prior to baseline visit (Day 0);&#xD;
&#xD;
          -  Hemoglobin &lt; 10 g/dL;&#xD;
&#xD;
          -  White blood cell (WBC) count &lt; 3,000/ mm^3 (equivalent to &lt; 3 x10^9/L);&#xD;
&#xD;
          -  Lymphocyte count &lt; 800/mm^3 (equivalent to &lt; 0.8 x10^9/L);&#xD;
&#xD;
          -  Absolute neutrophil count &lt; 1,500/mm^3 (equivalent to &lt; 1.5 x10^9/L);&#xD;
&#xD;
          -  Platelets &lt; 100,000/mm^3 (equivalent to &lt; 100 x 10^9/L);&#xD;
&#xD;
          -  Liver function test [aspartate aminotransferase (AST)], alanine aminotransferase&#xD;
             (ALT), or alkaline phosphatase (ALK)] results that are ≥ 2 times the upper limit of&#xD;
             normal (ULN);&#xD;
&#xD;
          -  Direct bilirubin &gt; ULN;&#xD;
&#xD;
          -  End stage renal disease [estimated glomerular filtration rate (eGFR) &lt; 20&#xD;
             ml/min/1.73m^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)&#xD;
             equation];&#xD;
&#xD;
          -  At or within three months of screening:&#xD;
&#xD;
               -  a positive QuantiFERON(R)-TB Gold test or positive purified protein derivative&#xD;
                  tuberculin skin test (PPD) [&gt;5mm induration, regardless of Bacille Calmette&#xD;
                  Guerin (BCG) vaccine administration] unless completion of treatment has been&#xD;
                  documented for active Tuberculosis (TB),&#xD;
&#xD;
               -  an indeterminate QuantiFERON (R)-TB Gold test unless followed by a subsequent&#xD;
                  negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation&#xD;
                  with and clearance by local infectious disease (ID) department.&#xD;
&#xD;
          -  Recent or ongoing active bacterial, viral, fungal, or opportunistic infections&#xD;
             requiring systemic anti-infective therapy;&#xD;
&#xD;
          -  Evidence of current or prior infection with human immunodeficiency virus (HIV),&#xD;
             hepatitis B [as assessed by HBsAg and anti-hepatitis B core antigen (HBc) Ab] or&#xD;
             hepatitis C [as assessed by anti-Hepatitis C Virus (anti-HCV) Ab];&#xD;
&#xD;
          -  Detectable circulating EBV or Cytomegalovirus (CMV) genomes or active infection;&#xD;
&#xD;
          -  Chronic infection that is currently being treated with suppressive anti-infective&#xD;
             therapy, including but not limited to tuberculosis, pneumocystis, CMV, herpes zoster,&#xD;
             and atypical mycobacteria, with the exception of historical orolabial or localized&#xD;
             cutaneous herpes simplex infections treated with suppressive anti- viral therapy;&#xD;
&#xD;
          -  Receipt of a live-attenuated vaccine within 12 months prior to screening;&#xD;
&#xD;
          -  Concomitant malignancies or a history of malignancy, with the exception of completely&#xD;
             treated basal cell carcinoma of the skin;&#xD;
&#xD;
          -  Pregnancy;&#xD;
&#xD;
          -  Lactating or breastfeeding;&#xD;
&#xD;
          -  Unwilling or unable to use reliable method(s) of contraception:&#xD;
&#xD;
               -  For females of child-bearing potential, from four weeks prior to Day 0 through&#xD;
&#xD;
                  1 year after Treg dosing;&#xD;
&#xD;
               -  For males, from the day of Treg infusion (baseline visit) to three months after&#xD;
                  Treg infusion.&#xD;
&#xD;
          -  Use of an investigational therapeutic medication, or other biologic medications except&#xD;
             rituximab, within the past 90 days, or 5 half-lives prior to screening, whichever is&#xD;
             greater;&#xD;
&#xD;
          -  Concomitant medical condition that places the subject at risk by participating in this&#xD;
             study, including but not limited to:&#xD;
&#xD;
               -  another severe, systemic autoimmune disease or condition (besides pemphigus)&#xD;
                  requiring systemic immunosuppressive therapy (e.g., rheumatoid arthritis,&#xD;
                  Systemic Lupus Erythematosus (SLE), systemic sclerosis, primary Sjogren's&#xD;
                  syndrome, primary vasculitis, psoriasis, multiple sclerosis, ankylosing&#xD;
                  spondylitis, and inflammatory bowel disease), or&#xD;
&#xD;
               -  severe, progressive, or poorly controlled renal, hepatic, hematological,&#xD;
                  gastrointestinal, pulmonary, cardiac, or neurological disease, or&#xD;
&#xD;
               -  history of significant infection or recurrent infection that, in the&#xD;
                  investigator's opinion, places the subject at risk by participating in this&#xD;
                  study, or&#xD;
&#xD;
               -  any other concomitant medical condition that, in the investigator's opinion,&#xD;
                  places the subject at risk by participating in this study.&#xD;
&#xD;
          -  Comorbidities requiring glucocorticoid therapy, including those which have required&#xD;
             three or more courses of systemic glucocorticoids within the previous 12 months;&#xD;
&#xD;
          -  Current or history within the past year of substance abuse; or&#xD;
&#xD;
          -  Inability to comply with study and follow-up procedures.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Haley Naik, MD,MHSc</last_name>
    <role>Study Chair</role>
    <affiliation>University of California San Francisco School of Medicine: Department of Dermatology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anna Haemel, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of California San Francisco School of Medicine: Department of Dermatology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Rosenblum, MD, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>University of California San Francisco School of Medicine: Department of Dermatology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeffrey Bluestone, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>UCSF School of Medicine: UCSF Diabetes Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Wofsy, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California San Francisco School of Medicine: Department of Dermatology</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Health Care: Department of Dermatology</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center: Department of Dermatology</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center: Department of Dermatology</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.niaid.nih.gov/</url>
    <description>National Institute of Allergy and Infectious Diseases (NIAID) website</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/about/dait</url>
    <description>Division of Allergy, Immunology, and Transplantation (DAIT) website</description>
  </link>
  <link>
    <url>http://www.autoimmunitycenters.org/</url>
    <description>Autoimmunity Centers of Excellence (ACE) website</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <results_first_submitted>October 22, 2021</results_first_submitted>
  <results_first_submitted_qc>October 22, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 22, 2021</results_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>autologous polyclonal regulatory T cell therapy</keyword>
  <keyword>PolyTregs</keyword>
  <keyword>open-label</keyword>
  <keyword>Phase 1 (safety)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pemphigus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.</ipd_description>
    <ipd_time_frame>On average, within 24 months after database lock for the trial.</ipd_time_frame>
    <ipd_access_criteria>Open access.</ipd_access_criteria>
    <ipd_url>https://www.immport.org/home</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 17, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03239470/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Ten participants were screened at four sites in the United States, and 5 of those participants initiated blood donation. Enrollment occurred between October 2017 and May 2020. The first participant was enrolled on October 10, 2017.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose</title>
          <description>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: Polyclonal Treg Infusion (Poly Tregs) High Dose</title>
          <description>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 2.5 x 10^8 PolyTregs. Study enrollment was closed prior to enrolling participants into Cohort 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Blood Donation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Polyclonal Treg Infusion</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5">Started includes all participants who completed the pre-infusion checklist at the infusion visit.</participants>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4">Participants who did not meet eligibility, per the pre-infusion checklist, did not complete study infusion.</participants>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Baseline Pemphigus Disease Area Index (PDAI) &gt;12, thus ineligible for PolyTregs infusion.</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants who donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs) that, after two weeks, received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose</title>
          <description>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.8" spread="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Pemphigus</title>
          <description>Summary of the type of diagnosed pemphigus at screening. To be eligible for the study, participants must have diagnosis of pemphigus vulgaris or pemphigus foliaceus.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Pemphigus Vulgaris</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Pemphigus Foliaceus</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at Diagnosis of Pemphigus</title>
          <description>Study participant's age in years at the time of pemphigus diagnosis.</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.5" spread="16.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Significant Adverse Events Through Week 52</title>
        <description>Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event (SAE). Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.&#xD;
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 52</time_frame>
        <population>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Polyclonal Treg Infusion (PolyTregs)</title>
            <description>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Significant Adverse Events Through Week 52</title>
          <description>Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event (SAE). Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.&#xD;
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
          <population>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</population>
          <units>Number of Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Significant Events Through Week 156</title>
        <description>Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event. Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs*, as determined by the safety review committee.&#xD;
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs) Related to Treatment, Polyclonal Tregs Infusion Through Week 52</title>
        <description>All adverse events (AEs) of specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) as a measure of safety and toxicity of the PolyTregs infusion*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 52</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Grade 3 to 5 Adverse Events (AEs) Through Week 52</title>
        <description>All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 52</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Grade 3 to 5 Adverse Events (AEs) Through Week 156</title>
        <description>All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Serious Adverse Events (SAEs) Through Week 156</title>
        <description>An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.&#xD;
**Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Infection-Related Adverse Events (AEs) Through Week 156</title>
        <description>Safety measure. Monitoring for signs and symptoms of infection-related AEs (e.g., viral, bacterial, or fungal organism, particularly opportunistic infections).</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Infusion-Related Reactions Within 24 Hours of PolyTregs Infusion</title>
        <description>Any infusion-related adverse events (AEs) Grade 1 or higher that occur within 24 hours of polyclonal Tregs* infusion. This study will grade the severity of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to 24 hours post infusion</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pemphigus Disease Area Index (PDAI)</title>
        <description>Pemphigus Disease Area Index (PDAI) is a cutaneous and mucosal disease activity assessment performed by the investigator, based on evaluation of lesions in well-defined anatomical locations. The score is weighted for the number and size of lesions, with a score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion(s), are scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranges from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.</description>
        <time_frame>From Baseline (Week 0) to Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Desmoglein (DSG) Autoantibody Titers</title>
        <description>Desmoglein (DSG) autoantibodies serum levels, measured by ELISA (enzyme-linked immunosorbent assay, compared to pre PolyTregs infusion DSG autoantibody levels*.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Initial Flare/Relapse by Week 156</title>
        <description>Time from initiation of polyTregs infusion* to the the time of the appearance of ≥3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the polyTregs infusion initiation.&#xD;
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants on a Prednisone Dose ≤10 Milligrams Per Day (mg/Day)</title>
        <description>A measure of efficacy. This will be assessed at Weeks 12, 26, 39, 52, 78, 104, 130, and 156.</description>
        <time_frame>Up to Week 156</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>52 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose</title>
          <description>Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (23.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <description>coronavirus infectious disease 19 (COVID-19)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Herpes simplex</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fascial rupture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Exostosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pemphigus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Enrollment was stopped early, on May 1, 2020, due to:&#xD;
Lack of recruitment,&#xD;
Ongoing and new feasibility issues, including the recent approval of rituximab for treatment of pemphigus, and&#xD;
The impact of the coronavirus infectious disease 19 (COVID-19) pandemic.&#xD;
No participants were enrolled in Cohort 2.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Director, Clinical Research Operations Program</name_or_title>
      <organization>DAIT/NIAID</organization>
      <phone>240-669-5064</phone>
      <email>DAITClinicalTrialsGov@niaid.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03239470
org study id: DAIT APG01
secondary id: APG01
secondary id: NIAID CRMS ID#: 37534
nct id: NCT03239470
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
T cells, a type of white blood cell called a lymphocyte, play an important role in the immune
      system. One subtype, the regulatory T cell (Treg) helps to regulate the immune system and may
      provide protection against the development of autoimmune disease. The hope is that these
      naturally occurring Treg cells can be utilized for the treatment of autoimmune disease and
      potentially replace the use of chronic immunosuppressive therapies that are associated with
      multiple side effects. There has been a small study showing safe administration of Tregs with
      decreased disease activity in patients with insulin-dependent diabetes. Tregs are being
      studied in lupus, cancer and organ transplantation.

      This phase I trial will be conducted as an open-label, dose-escalation, multicenter trial in
      adult participants with active pemphigus.The purpose of this study is to test the safety and
      effect of Treg therapy in participants who have skin (cutaneous) involvement due to
      pemphigus.
Up to 12 adults between the ages of 18 and 75 years of age who have been diagnosed with
      pemphigus and meet all other entry criteria will be enrolled to receive one infusion of their
      own expanded Tregs at one of the following doses:

        -  1.0 x 10^8 PolyTregs or

        -  2.5 x 10^8 PolyTregs.

      Safety, disease activity, and mechanism of action will be assessed over a three year period,
      using biospecimens from blood and skin. Study therapy administration will occur during an
      overnight stay, followed by 2 weekly visits, then monthly visits from Week 8 to Week 12, then
      quarterly visits from Week 26 to Week 52, then twice a year visits until Week 156.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Significant Adverse Events Through Week 52
time frame: Up to Week 52
description: Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event (SAE). Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Significant Events Through Week 156
time frame: Up to Week 156
description: Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event. Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs*, as determined by the safety review committee.
An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Participants With Adverse Events (AEs) Related to Treatment, Polyclonal Tregs Infusion Through Week 52
time frame: Up to Week 52
description: All adverse events (AEs) of specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) as a measure of safety and toxicity of the PolyTregs infusion*.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Grade 3 to 5 Adverse Events (AEs) Through Week 52
time frame: Up to Week 52
description: All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Grade 3 to 5 Adverse Events (AEs) Through Week 156
time frame: Up to Week 156
description: All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Serious Adverse Events (SAEs) Through Week 156
time frame: Up to Week 156
description: An SAE is any untoward medical occurrence that, at any dose* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
**Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Infection-Related Adverse Events (AEs) Through Week 156
time frame: Up to Week 156
description: Safety measure. Monitoring for signs and symptoms of infection-related AEs (e.g., viral, bacterial, or fungal organism, particularly opportunistic infections).
measure: Number of Infusion-Related Reactions Within 24 Hours of PolyTregs Infusion
time frame: Up to 24 hours post infusion
description: Any infusion-related adverse events (AEs) Grade 1 or higher that occur within 24 hours of polyclonal Tregs* infusion. This study will grade the severity of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Change From Baseline in Pemphigus Disease Area Index (PDAI)
time frame: From Baseline (Week 0) to Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156
description: Pemphigus Disease Area Index (PDAI) is a cutaneous and mucosal disease activity assessment performed by the investigator, based on evaluation of lesions in well-defined anatomical locations. The score is weighted for the number and size of lesions, with a score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion(s), are scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranges from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.
measure: Change From Baseline in Desmoglein (DSG) Autoantibody Titers
time frame: Up to Week 156
description: Desmoglein (DSG) autoantibodies serum levels, measured by ELISA (enzyme-linked immunosorbent assay, compared to pre PolyTregs infusion DSG autoantibody levels*.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Time to Initial Flare/Relapse by Week 156
time frame: Up to Week 156
description: Time from initiation of polyTregs infusion* to the the time of the appearance of ≥3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the polyTregs infusion initiation.
*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
measure: Number of Participants on a Prednisone Dose ≤10 Milligrams Per Day (mg/Day)
time frame: Up to Week 156
description: A measure of efficacy. This will be assessed at Weeks 12, 26, 39, 52, 78, 104, 130, and 156.
arm group label: Cohort 1: 1.0 x 10^8 PolyTregs
arm group type: Experimental
description: A single intravenous infusion of 1.0 x 10^8 PolyTregs will be administered.
arm group label: Cohort 2: 2.5x10^8 PolyTregs
arm group type: Experimental
description: A single intravenous infusion of 2.5x10^8 PolyTregs will be administered.
intervention type: Biological
intervention name: Cohort 1: 1.0 x 10^8 PolyTregs
description: Each participant will receive a target cell dose of 1.0 x 10^8 polyclonal Tregs.
arm group label: Cohort 1: 1.0 x 10^8 PolyTregs
other name: Polyclonal Regulatory T Cells
other name: autologous PolyTregs
other name: CD4+CD127lo/negCD25+ PolyTregs
intervention type: Biological
intervention name: Cohort 2: 2.5x10^8 PolyTregs
description: Each participant will receive a target cell dose of 2.5x10^8 polyclonal Tregs.
arm group label: Cohort 2: 2.5x10^8 PolyTregs
other name: Polyclonal Regulatory T Cells
other name: autologous PolyTregs
other name: CD4+CD127lo/negCD25+ PolyTregs
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Haley Naik, MD,MHSc
role: Study Chair
affiliation: University of California San Francisco School of Medicine: Department of Dermatology
last name: Anna Haemel, MD
role: Study Chair
affiliation: University of California San Francisco School of Medicine: Department of Dermatology
last name: Michael Rosenblum, MD, Ph.D.
role: Study Chair
affiliation: University of California San Francisco School of Medicine: Department of Dermatology
last name: Jeffrey Bluestone, Ph.D.
role: Study Chair
affiliation: UCSF School of Medicine: UCSF Diabetes Clinic
last name: David Wofsy, M.D.
role: Study Chair
affiliation: University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.niaid.nih.gov/
description: National Institute of Allergy and Infectious Diseases (NIAID) website
url: https://www.niaid.nih.gov/about/dait
description: Division of Allergy, Immunology, and Transplantation (DAIT) website
url: http://www.autoimmunitycenters.org/
description: Autoimmunity Centers of Excellence (ACE) website
responsible party type: Sponsor
mesh term: Pemphigus
sharing ipd: Yes
ipd description: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
ipd time frame: On average, within 24 months after database lock for the trial.
ipd access criteria: Open access.
ipd url: https://www.immport.org/home
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Enrollment was stopped early, on May 1, 2020, due to:
Lack of recruitment,
Ongoing and new feasibility issues, including the recent approval of rituximab for treatment of pemphigus, and
The impact of the coronavirus infectious disease 19 (COVID-19) pandemic.
No participants were enrolled in Cohort 2.
point of contact: 