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/NCT05986162</url>
    </required_header>
    <id_info>
      <org_study_id>BPL-ITO-DM-1001</org_study_id>
      <nct_id>NCT05986162</nct_id>
    </id_info>
    <brief_title>Safety and Preliminary Clinical Activity of Itolizumab in Dermatomyositis</brief_title>
    <official_title>A Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Clinical Activity of Itolizumab in Subjects With Dermatomyositis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Biotech Pharmaceutical Co., Ltd.</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Biotech Pharmaceutical Co., Ltd.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of Itolizumab&#xD;
        in subjects with Dermatomyositis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will enroll approximately 44 subjects in two parts:&#xD;
  &#xD;
        Part 1 is an open label, 3+3 single dose escalation and then mutiple dose administration&#xD;
        phase. 9~30 patients with DM are expected to be enrolled across 3 dose cohorts.&#xD;
  &#xD;
        Part 2 is a randomized phase and will enroll approximately 14 additional subjects, randomized&#xD;
        in a 1:1 ratio to one of the 2 doses based on efficacy data obtained from Part 1. All&#xD;
        participants in this study will receive Itolizumab intravenously every two weeks for a total&#xD;
        of 7 doses.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 30, 2023</start_date>
    <completion_date type="Anticipated">June 25, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 3, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of Treatment Emergent Adverse Events</measure>
      <time_frame>Study Week 20</time_frame>
      <description>Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Maximum serum concentration of Itolizumab, Cmax</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Maximum serum concentration of Itolizumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Minimum serum concentration of Itolizumab, Cmin</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Minimum serum concentration of Itolizumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to maximum serum concentration of Itolizumab, Tmax</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Time to maximum serum concentration of Itolizumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total Itolizumab exposure across time, AUC0-t</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Total Itolizumab exposure across time</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Half life of Itolizumab, t1/2</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Half life of Itolizumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IL-2</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers：IL-2</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IL-6</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers:IL-6</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TNF-α</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers: TNF-α</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IFN-γ</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers:IFN-γ</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CRP</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers:CRP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum ferritin</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers:Serum ferritin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ESR</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers:ESR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IgG</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers：IgG</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IgM</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers：IgM</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IgA</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Inflammatory Markers： IgA</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CD6 receptor expression levels</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Mean change of CD6 receptor expression levels in relative to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>T cell subsets</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Mean change of different proportion of T cell subsets in relative to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients achieving a TIS of ≥20</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Defined as patients with an increase of ≥20 points on the Total Improvement Score in relative to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients achieving DOI</measure>
      <time_frame>Study Week 16</time_frame>
      <description>DOI defined as ≥ 20% improvement in 3 of any 6 core set measures, with no more than 2 core set measures worsening by ≥ 25% (MMT-8 cannot worsen by ≥ 25%).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Change of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Defined as the mean change of activity score of CDASI（Score Range：0~132，The hingher score indcates the worse outcome） relative to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of ADA</measure>
      <time_frame>Study Week 16</time_frame>
      <description>Defined as the precentage of subjects presenting anti-drug antibody</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Exploratory indicators</measure>
      <time_frame>Study Week 16</time_frame>
      <description>To explore wether the change of the antibody can indcates the clinical efficiency of Itolizumab in DM patients</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">44</enrollment>
    <condition>Dermatomyositis, Adult Type</condition>
    <arm_group>
      <arm_group_label>Itolizumab Dose Level 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Itolizumab of 25 mg administered by intravenous infusion every 2 weeks for a total of 7 doses.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Itolizumab Dose Level 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Itolizumab of 50 mg administered by intravenous infusion every 2 weeks for a total of 7 doses.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Itolizumab Dose Level 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Itolizumab of 100 mg administered by intravenous infusion every 2 weeks for a total of 7 doses.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Itolizumab</intervention_name>
      <description>Patients to be treated with Itolizumab.</description>
      <arm_group_label>Itolizumab Dose Level 1</arm_group_label>
      <arm_group_label>Itolizumab Dose Level 2</arm_group_label>
      <arm_group_label>Itolizumab Dose Level 3</arm_group_label>
      <other_name>T1h</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female subject aged 18-75 years old (inclusive).&#xD;
  &#xD;
            2. Fulfill one of the following criteria for DM:1) Bohan and Peter criteria for definite&#xD;
               or probable DM;2) ENMC 2018 Dermatomyositis Classification Criteria&#xD;
  &#xD;
            3. Disease activity fulfills at least three of the following criteria:1) MMT-8 score &lt;&#xD;
               142; 2) physician's global disease activity ≥2 cm; 3) patient's global activity ≥2 cm;&#xD;
               4) extra-muscular activity ≥2 cm; 5) Health Assessment Questionnaire [HAQ] ≥0.25; 6)&#xD;
               at least one muscle enzyme &gt;1.5 times ULN&#xD;
  &#xD;
            4. Under treatment with corticosteroids and/or at least 1 immunesuppressant, and being on&#xD;
               stable therapy for at least 4 and 8 weeks for corticosteroids and immunesuppressant&#xD;
               respectively (see Section 5.7.1)&#xD;
  &#xD;
            5. Fulfill all of the following criteria: 1) % predicted values of FVC≥70%; 2) %&#xD;
               predicted values of DLCO≥60%; 3) chest HRCT indicating the extent of disease lesion of&#xD;
               DM-ILD &lt; 20% as determined by the investigator&#xD;
  &#xD;
            6. Negative result of serum HCG within 72 hours before enrollment for female with&#xD;
               potential fertility&#xD;
  &#xD;
            7. Able to understand and comply with the planned procedure as required by the protocol,&#xD;
               and sign a written informed consent form (ICF)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subject with other connective tissue diseases (e.g., systemic sclerosis, systemic&#xD;
               lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, Sjogren's syndrome,&#xD;
               mixed connective tissue disease, etc.) or ANCA associated vasculitis.&#xD;
  &#xD;
            2. Diagnosed with polymyositis or IMNM.&#xD;
  &#xD;
            3. Diagnosed with systemic, severe musculoskeletal disorder that unrelated to DM and will&#xD;
               interfere with the investigator's assessment of the subject's muscle strength.&#xD;
  &#xD;
            4. Subject who plans to start a physical therapy program during the trial.&#xD;
  &#xD;
            5. Subject who has a medical history of New York Heart Association class III or IV&#xD;
               congestive heart failure, clinically significant or uncontrolled unstable angina or&#xD;
               myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months&#xD;
               prior to screening&#xD;
  &#xD;
            6. Subject with impaired renal function (serum creatinine &gt; 1.5 x ULN or creatinine&#xD;
               clearance &lt; 30 mL/min [Cockcroft-Gault formula]) at screening.&#xD;
  &#xD;
            7. Any of following significant abnormalities in liver function at screening:&#xD;
  &#xD;
                 1. Serum alanine transaminase (ALT) or glutathione transaminase (AST) ≥ 3 x ULN,&#xD;
                    except when judged by the investigator to be due to DM;&#xD;
  &#xD;
                 2. Total bilirubin ≥ 1.5 x ULN;&#xD;
  &#xD;
                 3. Cirrhosis classification of Child-Pugh grade C.&#xD;
  &#xD;
            8. Any of the following abnormalities at screening:&#xD;
  &#xD;
                 1. Hepatitis B-related tests: ① positive hepatitis B surface antigen (HBsAg); ②&#xD;
                    positive hepatitis B core antibody (HBcAb); ③ positive hepatitis B surface&#xD;
                    antibody (HBsAb) and no history of hepatitis B vaccination; ④ positive hepatitis&#xD;
                    B e antigen or hepatitis B e antibody;&#xD;
  &#xD;
                 2. Positive hepatitis C virus nucleic acid test (HCV-RNA);&#xD;
  &#xD;
                 3. Positive acquired immunodeficiency syndrome antibody (HIV-Ab);&#xD;
  &#xD;
                 4. Positive anti-syphilis spiral antibody (TP-Ab);&#xD;
  &#xD;
                 5. Other acute or chronic infections requiring treatment.&#xD;
  &#xD;
            9. Absolute lymphocyte count &lt; 0.5×109/L at screening&#xD;
  &#xD;
           10. Subject who has a medical history of tuberculosis or those who deny a history of&#xD;
               tuberculosis but has a positive gamma-interferon release test at screening.&#xD;
  &#xD;
           11. Any other clinically significant clinical condition or laboratory tests abnormality&#xD;
               that, in the judgment of the investigator, may affect the safety evaluation&#xD;
  &#xD;
           12. Any malignant tumor other than the cured carcinoma in situ or basal cell carcinoma&#xD;
               within 5 years before screening&#xD;
  &#xD;
           13. Suspected allergic to the investigational drug or any of its excipients&#xD;
  &#xD;
           14. Subject who had participated in other clinical studies (other than those not receiving&#xD;
               interventions, such as observational study or questionnaires survey) within 3 months&#xD;
               prior to screening, or who are participating in other experimental treatments.&#xD;
  &#xD;
           15. Subject who requires to be administrated with higher dose of corticosteroids and/or&#xD;
               immunesuppressant than the allowed maximum dose specified in the protocol (section&#xD;
               5.7.1)&#xD;
  &#xD;
           16. Subject who had been treated by one or more of the following drugs during the&#xD;
               corresponding time window prior to screening:&#xD;
  &#xD;
                 1. cyclophosphamide, rituximab within 12 months prior to screening;&#xD;
  &#xD;
                 2. belizumab, tetrasip within 24 weeks prior to screening;&#xD;
  &#xD;
                 3. intravenous immunoglobulin injections, baliximab, infliximab, adalimumab,&#xD;
                    tolimumab, JAK inhibitors within 12 weeks prior to screening;&#xD;
  &#xD;
                 4. Other monoclonal antibodies or other biological agents within 12 weeks or 5&#xD;
                    half-lives [whichever is longer] prior to screening.&#xD;
  &#xD;
           17. Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable&#xD;
               method to avoid pregnancy during study and within 3 months after the last study&#xD;
               treatment&#xD;
  &#xD;
           18. As determined by the investigator, any medical, psychiatric, or other condition or&#xD;
               circumstance that is likely to negatively affect the reliability of the study data.&#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>Xiaofeng Zeng</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Rui Chen</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xijuan Song</last_name>
      <phone>010-51571020</phone>
      <email>songxijuan@biotechplc.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 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>Dermatomyositis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05986162
  org study id: BPL-ITO-DM-1001
  nct id: NCT05986162
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  To evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of Itolizumab
        in subjects with Dermatomyositis.
  The study will enroll approximately 44 subjects in two parts:
  
        Part 1 is an open label, 3+3 single dose escalation and then mutiple dose administration
        phase. 9~30 patients with DM are expected to be enrolled across 3 dose cohorts.
  
        Part 2 is a randomized phase and will enroll approximately 14 additional subjects, randomized
        in a 1:1 ratio to one of the 2 doses based on efficacy data obtained from Part 1. All
        participants in this study will receive Itolizumab intravenously every two weeks for a total
        of 7 doses.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Treatment Emergent Adverse Events
  time frame: Study Week 20
  description: Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0
  measure: Maximum serum concentration of Itolizumab, Cmax
  time frame: Study Week 16
  description: Maximum serum concentration of Itolizumab
  measure: Minimum serum concentration of Itolizumab, Cmin
  time frame: Study Week 16
  description: Minimum serum concentration of Itolizumab
  measure: Time to maximum serum concentration of Itolizumab, Tmax
  time frame: Study Week 16
  description: Time to maximum serum concentration of Itolizumab
  measure: Total Itolizumab exposure across time, AUC0-t
  time frame: Study Week 16
  description: Total Itolizumab exposure across time
  measure: Half life of Itolizumab, t1/2
  time frame: Study Week 16
  description: Half life of Itolizumab
  measure: IL-2
  time frame: Study Week 16
  description: Inflammatory Markers：IL-2
  measure: IL-6
  time frame: Study Week 16
  description: Inflammatory Markers:IL-6
  measure: TNF-α
  time frame: Study Week 16
  description: Inflammatory Markers: TNF-α
  measure: IFN-γ
  time frame: Study Week 16
  description: Inflammatory Markers:IFN-γ
  measure: CRP
  time frame: Study Week 16
  description: Inflammatory Markers:CRP
  measure: Serum ferritin
  time frame: Study Week 16
  description: Inflammatory Markers:Serum ferritin
  measure: ESR
  time frame: Study Week 16
  description: Inflammatory Markers:ESR
  measure: IgG
  time frame: Study Week 16
  description: Inflammatory Markers：IgG
  measure: IgM
  time frame: Study Week 16
  description: Inflammatory Markers：IgM
  measure: IgA
  time frame: Study Week 16
  description: Inflammatory Markers： IgA
  measure: CD6 receptor expression levels
  time frame: Study Week 16
  description: Mean change of CD6 receptor expression levels in relative to baseline
  measure: T cell subsets
  time frame: Study Week 16
  description: Mean change of different proportion of T cell subsets in relative to baseline
  measure: Proportion of patients achieving a TIS of ≥20
  time frame: Study Week 16
  description: Defined as patients with an increase of ≥20 points on the Total Improvement Score in relative to baseline.
  measure: Proportion of patients achieving DOI
  time frame: Study Week 16
  description: DOI defined as ≥ 20% improvement in 3 of any 6 core set measures, with no more than 2 core set measures worsening by ≥ 25% (MMT-8 cannot worsen by ≥ 25%).
  measure: Mean Change of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score
  time frame: Study Week 16
  description: Defined as the mean change of activity score of CDASI（Score Range：0~132，The hingher score indcates the worse outcome） relative to baseline.
  measure: Incidence of ADA
  time frame: Study Week 16
  description: Defined as the precentage of subjects presenting anti-drug antibody
  measure: Exploratory indicators
  time frame: Study Week 16
  description: To explore wether the change of the antibody can indcates the clinical efficiency of Itolizumab in DM patients
  arm group label: Itolizumab Dose Level 1
  arm group type: Experimental
  description: Itolizumab of 25 mg administered by intravenous infusion every 2 weeks for a total of 7 doses.
  arm group label: Itolizumab Dose Level 2
  arm group type: Experimental
  description: Itolizumab of 50 mg administered by intravenous infusion every 2 weeks for a total of 7 doses.
  arm group label: Itolizumab Dose Level 3
  arm group type: Experimental
  description: Itolizumab of 100 mg administered by intravenous infusion every 2 weeks for a total of 7 doses.
  intervention type: Drug
  intervention name: Itolizumab
  description: Patients to be treated with Itolizumab.
  arm group label: Itolizumab Dose Level 1
  arm group label: Itolizumab Dose Level 2
  arm group label: Itolizumab Dose Level 3
  other name: T1h
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Xiaofeng Zeng
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: Rui Chen
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: Xijuan Song
  phone: 010-51571020
  email: songxijuan@biotechplc.com
  responsible party type: Sponsor
  mesh term: Dermatomyositis
  sharing ipd: No