xml: <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/NCT05969717</url>
    </required_header>
    <id_info>
      <org_study_id>K3016</org_study_id>
      <nct_id>NCT05969717</nct_id>
    </id_info>
    <brief_title>Induced Pluripotent Stem Cell Derived Exosomes for the Treatment of Atopic Dermatitis</brief_title>
    <official_title>Exploratory Clinical Study on Induced Pluripotent Stem Cell Derived Exosomes (GD-iExo-001) for the Treatment of Atopic Dermatitis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Guidon Pharmaceutics Ltd.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Peking Union Medical College Hospital</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>
        Evaluate the safety, tolerability, and preliminary efficacy of GD-iExo-001 in the treatment&#xD;
        of atopic dermatitis&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterised by&#xD;
        intense itching and recurrent eczematous lesions. Although it most often starts in infancy&#xD;
        and affects two of ten children, it is also highly prevalent in adults. It is the leading&#xD;
        non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial&#xD;
        burden on patients and their relatives, and increases the risk of food allergy, asthma,&#xD;
        allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders.&#xD;
        Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2&#xD;
        response and exaggerated IgE responses to allergens, it is now recognised as a lifelong&#xD;
        disposition with variable clinical manifestations and expressivity, in which defects of the&#xD;
        epidermal barrier are central. Present prevention and treatment focus on restoration of&#xD;
        epidermal barrier function, which is best achieved through the use of emollients. Topical&#xD;
        corticosteroids are still the first-line therapy for acute flares, but they are also used&#xD;
        proactively along with topical calcineurin inhibitors to maintain remission.&#xD;
  &#xD;
        Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of&#xD;
        multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos&#xD;
        of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or&#xD;
        distant cells far from their release, reprogramming the recipient cells upon their bioactive&#xD;
        compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo,&#xD;
        cell-targeting specificity are of immense biological interest considering extremely high&#xD;
        potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic&#xD;
        nanocarriers.&#xD;
  &#xD;
        Induced pluripotent stem cells (iPSCs) are pluripotent stem cells generated from adult cells&#xD;
        by reprogramming. iPSCs have the same properties as embryonic stem cells, and therefore&#xD;
        self-renew and can differentiate into all cell types of the body except for cells in&#xD;
        extra-embryonic tissues such as the placenta. iPSC-derived exosomes contain TGF- β、 BDNF&#xD;
        etc., which can inhibit cell apoptosis, inhibit inflammatory response, promote angiogenesis,&#xD;
        inhibit fibrosis, and enhance tissue repair potential, with a wide range of potential&#xD;
        applications. iPSC-derived exosomes have emerged as an important paracrine factor for iPSCs&#xD;
        to repair injured cells through the delivery of bioactive components.&#xD;
  &#xD;
        The purpose of this trial is to evaluate the safety, tolerability, and preliminary efficacy&#xD;
        of iPSC-derived exosomes in the treatment of atopic dermatitis.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 12, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2025</primary_completion_date>
    <phase>Early Phase 1</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>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>adverse events as assessed by CTCAE</measure>
      <time_frame>42 days from post-administration</time_frame>
      <description>all potentially treated subjects to assess the safety</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The proportion of subjects whose IGA score improved by 2 points or more compared with the baseline score.</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The proportion of subjects with an IGA score of 0-1 and an improvement of 2 or more over the baseline score</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The proportion of subjects whose EASI score improved by more than 50% compared with the baseline period</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The proportion of subjects whose EASI score improved by more than 75% compared with the baseline period</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The proportion of subjects whose EASI score improved by more than 90% compared with the baseline period</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in the score of the NRS</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in the score of the DLQI</measure>
      <time_frame>Screening, after the first administration 8 day, 15 days, 21 days, 42 days</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Atopic Dermatitis</condition>
    <arm_group>
      <arm_group_label>GD-iExo-001 treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group1 (low-dose group), 8 papatients are treated with 10 μg/mL GD-iExo-001. Group2 (high-dose group), 8 papatients are treated with 50 μg/mL GD-iExo-001. One drop (about 50 μL) of GD-iExo-001 was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Normal saline control</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Group1 (low-dose group), 2 papatients are treated with normal saline. Group2 (high-dose group), 2 papatients are treated with normal saline. One drop (about 50 μL) of normal saline was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>GD-iExo-001</intervention_name>
      <description>One drop (about 50 μL) of GD-iExo-001 was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.</description>
      <arm_group_label>GD-iExo-001 treatment</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>normal saline</intervention_name>
      <description>One drop (about 50 μL) of normal saline was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.</description>
      <arm_group_label>Normal saline control</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 18 to 70 years, body mass index (BMI) between 18 and 35 kg/m2 (including boundary&#xD;
               values);&#xD;
  &#xD;
            -  Overall good health except AD;&#xD;
  &#xD;
            -  Participants diagnosed with atopic dermatitis (AD) as defined by the Hanifin and Rajka&#xD;
               criteria;&#xD;
  &#xD;
            -  Investigator overall assessment (IGA) score of 2 to 3;&#xD;
  &#xD;
            -  Participants with a history of subacute or chronic AD symptoms for at least 6 months;&#xD;
  &#xD;
            -  Participants with body surface area (BSA) of AD involvement of ≤5% at screening and&#xD;
               baseline;&#xD;
  &#xD;
            -  Participants and their partners agreed to use effective contraception throughout the&#xD;
               study period (from screening to 3 months after completion of treatment);&#xD;
  &#xD;
            -  Participants understood and voluntarily signed the informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  There are obvious active systemic or local infections, including but not limited to&#xD;
               the infection of AD secondary infection, local bacterial infection in target lesion,&#xD;
               local viral infection in target lesion, and local fungal infection in target lesion.&#xD;
               Note: After the infection resolves, the patients can be re-screened;&#xD;
  &#xD;
            -  Presence of any of the following conditions: HB surface antigen (HBsAg) positive and /&#xD;
               or HB e antigen (HBeAg) positive, HB e antibody (HBeAb) and / or hepatitis B core&#xD;
               antibody (HBcAb) positive and hepatitis B virus deoxyribonucleic acid (HBV-DNA) copy&#xD;
               number&gt; 2000 IU / mL; limited hepatitis C virus (HCV) antibody positive and peripheral&#xD;
               blood hepatitis C virus (HCV) RNA positive; positive human immunodeficiency virus&#xD;
               (HIV) antibody; positive for syphilis (TPA) test;&#xD;
  &#xD;
            -  Inoculate live or attenuated vaccine within 4 weeks before screening or during the&#xD;
               study period;&#xD;
  &#xD;
            -  Received allergen specific immunotherapy within 6 months before screening;&#xD;
  &#xD;
            -  Use of topical drugs known or may affect AD within 2 weeks before screening (including&#xD;
               but not limited to topical glucocorticoids; calcineurin inhibitors: such as&#xD;
               tacrolimus, pirolimus, etc.);&#xD;
  &#xD;
            -  Use of immunosuppressants and Janus kinase inhibitors within 4 weeks before screening;&#xD;
  &#xD;
            -  Use of any biological agent (such as IL-4 receptor inhibitors, IL-13 inhibitors) for&#xD;
               12 weeks before screening or 5 half-lives (whichever is longer);&#xD;
  &#xD;
            -  Received systemic or local Chinese medicine treatment (including Chinese medicine&#xD;
               immersion treatment) within 2 weeks before screening;&#xD;
  &#xD;
            -  Treated with UV and photochemistry within 4 weeks prior to screening;&#xD;
  &#xD;
            -  Required systemic treatment of antiviral, antiparasitic, antigenic, or antifungals&#xD;
               within 4 weeks prior to screening;&#xD;
  &#xD;
            -  With significant abnormal findings or laboratory values and clinical significance,&#xD;
               such as white blood cell count &lt;3.0e9 / L; neutrophils &lt;1 LLN; hemoglobin &lt;90g / L;&#xD;
               platelet &lt;100e9 / L; serum creatinine&gt; 1.5 ULN, ALT or AST 2 ULN; QTcF&gt; 450 msec&#xD;
               (male) or QTcF&gt; 470 msec (female);&#xD;
  &#xD;
            -  Other combined (or co-occurrence) skin diseases that may affect the study evaluation,&#xD;
               such as acne, psoriasis, lupus erythematosus, etc.; or large tattoos, birthmarks, skin&#xD;
               scars, skin ulcers and other conditions that may affect the judgment of the&#xD;
               investigator;&#xD;
  &#xD;
            -  Except for AD, any history of clinical major disease or clinically significant&#xD;
               circulatory system abnormality, endocrine system abnormality, neurological or&#xD;
               hematological disorders, immune system disease, psychiatric illness and metabolic&#xD;
               instability; clinical significance is defined as the risk of the safety of the subject&#xD;
               or aggravating the disease / disease during the study;&#xD;
  &#xD;
            -  Patients with a history of severe skin allergy and / or allergy to any ingredients of&#xD;
               the product;&#xD;
  &#xD;
            -  History of cancer in the past 5 years (except for surgically removed squamous cell&#xD;
               carcinoma, basal cell carcinoma, or skin carcinoma in situ);&#xD;
  &#xD;
            -  Any major surgery within 8 weeks before screening; or subjects expected to undergo&#xD;
               surgery during the trial or within 4 weeks after the end of the trial; or 400 mL&#xD;
               nonphysiological blood loss (including trauma, blood collection, blood donation within&#xD;
               12 weeks before screening);&#xD;
  &#xD;
            -  Pregnant women, lactating women, or women who plan to become pregnant during the study&#xD;
               (fertile women must have a urine pregnancy test with negative results);&#xD;
  &#xD;
            -  Subjects who are currently participating in other clinical trials or who have&#xD;
               participated in other clinical trials within 90 days;&#xD;
  &#xD;
            -  The investigator judged any other condition not suitable to participate in this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hongzhong Jin, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ju Qiao, PhD</last_name>
      <phone>+8615201125788</phone>
      <email>qiaoqiaoju@aliyun.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Chinese Academy of Medical Science &amp; Peking Union Medical College Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100730</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ju Qiao, PhD</last_name>
        <phone>+8615201125788</phone>
        <email>qiaoqiaoju@aliyun.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 23, 2023</study_first_submitted>
    <study_first_submitted_qc>July 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 23, 2023</last_update_submitted>
    <last_update_submitted_qc>July 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</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>Dermatitis, Atopic</mesh_term>
      <mesh_term>Dermatitis</mesh_term>
      <mesh_term>Eczema</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05969717
  org study id: K3016
  nct id: NCT05969717
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  Evaluate the safety, tolerability, and preliminary efficacy of GD-iExo-001 in the treatment
        of atopic dermatitis
  Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterised by
        intense itching and recurrent eczematous lesions. Although it most often starts in infancy
        and affects two of ten children, it is also highly prevalent in adults. It is the leading
        non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial
        burden on patients and their relatives, and increases the risk of food allergy, asthma,
        allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders.
        Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2
        response and exaggerated IgE responses to allergens, it is now recognised as a lifelong
        disposition with variable clinical manifestations and expressivity, in which defects of the
        epidermal barrier are central. Present prevention and treatment focus on restoration of
        epidermal barrier function, which is best achieved through the use of emollients. Topical
        corticosteroids are still the first-line therapy for acute flares, but they are also used
        proactively along with topical calcineurin inhibitors to maintain remission.
  
        Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of
        multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos
        of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or
        distant cells far from their release, reprogramming the recipient cells upon their bioactive
        compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo,
        cell-targeting specificity are of immense biological interest considering extremely high
        potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic
        nanocarriers.
  
        Induced pluripotent stem cells (iPSCs) are pluripotent stem cells generated from adult cells
        by reprogramming. iPSCs have the same properties as embryonic stem cells, and therefore
        self-renew and can differentiate into all cell types of the body except for cells in
        extra-embryonic tissues such as the placenta. iPSC-derived exosomes contain TGF- β、 BDNF
        etc., which can inhibit cell apoptosis, inhibit inflammatory response, promote angiogenesis,
        inhibit fibrosis, and enhance tissue repair potential, with a wide range of potential
        applications. iPSC-derived exosomes have emerged as an important paracrine factor for iPSCs
        to repair injured cells through the delivery of bioactive components.
  
        The purpose of this trial is to evaluate the safety, tolerability, and preliminary efficacy
        of iPSC-derived exosomes in the treatment of atopic dermatitis.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: adverse events as assessed by CTCAE
  time frame: 42 days from post-administration
  description: all potentially treated subjects to assess the safety
  measure: The proportion of subjects whose IGA score improved by 2 points or more compared with the baseline score.
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  measure: The proportion of subjects with an IGA score of 0-1 and an improvement of 2 or more over the baseline score
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  measure: The proportion of subjects whose EASI score improved by more than 50% compared with the baseline period
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  measure: The proportion of subjects whose EASI score improved by more than 75% compared with the baseline period
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  measure: The proportion of subjects whose EASI score improved by more than 90% compared with the baseline period
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  measure: Change in the score of the NRS
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  measure: Change in the score of the DLQI
  time frame: Screening, after the first administration 8 day, 15 days, 21 days, 42 days
  arm group label: GD-iExo-001 treatment
  arm group type: Experimental
  description: Group1 (low-dose group), 8 papatients are treated with 10 μg/mL GD-iExo-001. Group2 (high-dose group), 8 papatients are treated with 50 μg/mL GD-iExo-001. One drop (about 50 μL) of GD-iExo-001 was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.
  arm group label: Normal saline control
  arm group type: Placebo Comparator
  description: Group1 (low-dose group), 2 papatients are treated with normal saline. Group2 (high-dose group), 2 papatients are treated with normal saline. One drop (about 50 μL) of normal saline was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.
  intervention type: Drug
  intervention name: GD-iExo-001
  description: One drop (about 50 μL) of GD-iExo-001 was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.
  arm group label: GD-iExo-001 treatment
  intervention type: Other
  intervention name: normal saline
  description: One drop (about 50 μL) of normal saline was given to the affected skin area of 2-4 cm2 for 14 consecutive days, twice per day.
  arm group label: Normal saline control
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Hongzhong Jin, MD
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: Ju Qiao, PhD
  phone: +8615201125788
  email: qiaoqiaoju@aliyun.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Dermatitis, Atopic
  mesh term: Dermatitis
  mesh term: Eczema