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/NCT05978544</url>
    </required_header>
    <id_info>
      <org_study_id>BPL-ITO-ARDS-1001</org_study_id>
      <nct_id>NCT05978544</nct_id>
    </id_info>
    <brief_title>Safety and Preliminary Clinical Activity of Itolizumab in ARDS</brief_title>
    <official_title>A Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Clinical Activity of Itolizumab in Subjects With Acute Respiratory Distress Syndrome Caused by Infectious Pneumonia</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>
      <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 clinical activity of Itolizumab in subjects&#xD;
        with acute respiratory distress syndrome (ARDS) caused by Infectious Pneumonia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will enroll approximately 38 subjects in two parts:&#xD;
  &#xD;
        Part 1 is an open label 3+3 single dose escalation phase. 9-24 patients with ARDS caused by&#xD;
        infectious pneumonia across 3 dose cohorts.&#xD;
  &#xD;
        Part 2 is a randomized phase and will enroll approximately 14 additional participants,&#xD;
        randomized in a 1:1 ratio to one of the 2 doses based on efficacy data obtained from Part 1.&#xD;
  &#xD;
        All participants in this study will receive Itolizumab intravenously for once, investigator&#xD;
        discretion to continue with the same dose every 3 days up to 7 days.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 31, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 30, 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 Day 58</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 Day 30</time_frame>
      <description>Maximum serum concentration of Itolizumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Minimum serum concentration of Itolizumab, Cmin</measure>
      <time_frame>Study Day 30</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 Day 30</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 Day 30</time_frame>
      <description>Total Itolizumab exposure across time</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Half life of Itolizumab, t1/2</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Half life of Itolizumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory Markers,IL-6</measure>
      <time_frame>Study Day 30</time_frame>
      <description>IL-6</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory Markers,TNF-α</measure>
      <time_frame>Study Day 30</time_frame>
      <description>TNF-α</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory Markers, hs-CRP</measure>
      <time_frame>Study Day 30</time_frame>
      <description>hs-CRP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory Markers,Serum ferritin</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Serum ferritin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory Markers,D-dimer</measure>
      <time_frame>Study Day 30</time_frame>
      <description>D-dimer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CD6 receptor expression levels</measure>
      <time_frame>Study Day 30</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 Day 30</time_frame>
      <description>Mean change of different T cell subsets in relative to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The proportion of patients with stable or improved Lung Function</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Defined as patients with stable or improved PaO2 without increasing FiO2 in relative to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean change from baseline in Murray Score</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Mean change of Murray Score in relative to baseline，The higher score means the worse outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean change from baseline in SOFA score</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Mean change of SOFA（Sequential Organ Failure Assessment） score in relative to baseline，The higher score means the worse outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mechanical ventilation-free days</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Duration of non-Mechanical ventilation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Oxygen therapy-free days</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Duration of non-Oxygen therapy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of ICU stay</measure>
      <time_frame>Study Day 30</time_frame>
      <description>ICU stay days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality rate</measure>
      <time_frame>Study Day 15, 30</time_frame>
      <description>Defined as the proportion of patients who met fatal outcome event by Day 15 and 30</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical status assessed using a 7-category ordinal scale</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Clinical status assessed using a 7-category ordinal scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of ADA</measure>
      <time_frame>Study Day 30</time_frame>
      <description>Defined as the precentage of subjects presenting anti-drug antibody</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">38</enrollment>
    <condition>Acute Respiratory Distress Syndrome</condition>
    <arm_group>
      <arm_group_label>Itolizumab Dose Level 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Itolizumab of 50 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.</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 100 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.</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 150 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.</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. Clinical diagnosis with infectious pneumonia as determined by the investigator&#xD;
  &#xD;
            3. Subject who havd received anti-infective treatment according to clinical practice.&#xD;
  &#xD;
            4. Diagnosis with ARDS according to the following criteria: (i) Bilateral opacities-not&#xD;
               fully explained by effusions, lobar/lung collapse, or nodules; (ii) respiratory&#xD;
               failure not fully explained by cardiac failure or fluid overload; (iii) Oxygenation&#xD;
               (PaO2/FiO2) ≤300.&#xD;
  &#xD;
            5. ARDS diagnosed within 48 hours before administration, and fullfil the criteria of ARDS&#xD;
               before administration&#xD;
  &#xD;
            6. Fullfill at least 2 of the following 4 criteria: ① elevated hs-CRP (&gt;6 ULN); ②&#xD;
               elevated IL-6 (&gt;3 ULN); ③ high serum ferritin (&gt;500µg/L at any one time or more than&#xD;
               2-fold increase within 48 hours of onset); ④ high D-dimer (&gt;3 ULN).&#xD;
  &#xD;
            7. Negative result of serum HCG within 72 hours before enrollment for female with&#xD;
               potential fertility&#xD;
  &#xD;
            8. Participant or his/her legal representive (when the participant is not capable of&#xD;
               giving consent) is able to understand and comply with the planned procedure as&#xD;
               required by the protocol, and sign a written informed consent form (ICF)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. ARDS caused by non-infectious pneumonia (e.g., burns, drowning, poisoning, etc.)&#xD;
  &#xD;
            2. Subject who has cardiogenic pulmonary edema, and it is the main cause of respiratory&#xD;
               failure&#xD;
  &#xD;
            3. Subject who is at high risk of death within 24 hours regardless of the treatment&#xD;
               measures given as determined by the investigator&#xD;
  &#xD;
            4. Subject who is receiving extracorporeal membrane pulmonary oxygenation (ECMO) therapy&#xD;
               at the time of screening.&#xD;
  &#xD;
            5. Subject who had received mechanical ventilation for more than 72 hours prior to&#xD;
               administration.&#xD;
  &#xD;
            6. Subject with active tumors (other than carcinoma in situ or basal cell carcinoma) that&#xD;
               requiring treatment.&#xD;
  &#xD;
            7. Any of the following chronic organ damage or immunosuppression:&#xD;
  &#xD;
                 1. Cardiac: cardiac arrest within 7 days prior to screening; New York Heart&#xD;
                    Association cardiac function class IV at screening;&#xD;
  &#xD;
                 2. Pulmonary: oxygen therapy or ventilator-dependent therapy for more than 1 month&#xD;
                    cumulatively within 6 months prior to screening; pulmonary embolism within 4&#xD;
                    weeks prior to screening; pulmonary hypertension, end-stage lung disease, or&#xD;
                    interstitial lung disease requiring glucocorticoid therapy at screening;&#xD;
  &#xD;
                 3. Renal: serum creatinine &gt; 1.5 ULN or creatinine clearance &lt; 30 mL/min at&#xD;
                    screening (Cockcroft-Gault formula, see study protocol annex 5 for details) or on&#xD;
                    long-term dialysis treatment;&#xD;
  &#xD;
                 4. Liver: liver function classification of Child-Pugh grade C at screening;&#xD;
  &#xD;
                 5. Immunosuppression status: with lymphoma, leukemia or acquired immunodeficiency;&#xD;
                    having received antitumor chemotherapy in the last 3 months, or being treated&#xD;
                    with immunosuppression for organ transplantation or immune disorders; having had&#xD;
                    allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell&#xD;
                    transplantation.&#xD;
  &#xD;
            8. Subject who had vaccination within 28 days prior to administration, or plan to get the&#xD;
               vaccine during the study period&#xD;
  &#xD;
            9. Any of the following abnormalities at screening&#xD;
  &#xD;
                 1. Hepatitis B-related tests: ① positive for hepatitis B surface antigen (HBsAg); ②&#xD;
                    positive for hepatitis B core antibody (HBcAb); ③ positive for hepatitis B&#xD;
                    surface antibody (HBsAb) and no history of hepatitis B vaccination; ④ positive&#xD;
                    for hepatitis B e antigen or hepatitis B e antibody;&#xD;
  &#xD;
                 2. Positive hepatitis C virus antibody (HCV-Ab);&#xD;
  &#xD;
                 3. Positive acquired immunodeficiency syndrome antibody (HIV-Ab).&#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. Absolute lymphocyte count &lt; 0.2×109/L at screening&#xD;
  &#xD;
           12. Suspected allergic to the investigational drug or any of its excipients&#xD;
  &#xD;
           13. 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;
           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. 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>Bin Du</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Huadong Zhu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>DANDAN Gao</last_name>
      <phone>010-51571020</phone>
      <email>gaodandan@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 7, 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 7, 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>Respiratory Distress Syndrome</mesh_term>
      <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
      <mesh_term>Acute Lung Injury</mesh_term>
      <mesh_term>Syndrome</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/NCT05978544
  org study id: BPL-ITO-ARDS-1001
  nct id: NCT05978544
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  To evaluate the safety, tolerability, PK, PD, and clinical activity of Itolizumab in subjects
        with acute respiratory distress syndrome (ARDS) caused by Infectious Pneumonia.
  The study will enroll approximately 38 subjects in two parts:
  
        Part 1 is an open label 3+3 single dose escalation phase. 9-24 patients with ARDS caused by
        infectious pneumonia across 3 dose cohorts.
  
        Part 2 is a randomized phase and will enroll approximately 14 additional participants,
        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 for once, investigator
        discretion to continue with the same dose every 3 days up to 7 days.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Treatment Emergent Adverse Events
  time frame: Study Day 58
  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 Day 30
  description: Maximum serum concentration of Itolizumab
  measure: Minimum serum concentration of Itolizumab, Cmin
  time frame: Study Day 30
  description: Minimum serum concentration of Itolizumab
  measure: Time to maximum serum concentration of Itolizumab, Tmax
  time frame: Study Day 30
  description: Time to maximum serum concentration of Itolizumab
  measure: Total Itolizumab exposure across time, AUC0-t
  time frame: Study Day 30
  description: Total Itolizumab exposure across time
  measure: Half life of Itolizumab, t1/2
  time frame: Study Day 30
  description: Half life of Itolizumab
  measure: Inflammatory Markers,IL-6
  time frame: Study Day 30
  description: IL-6
  measure: Inflammatory Markers,TNF-α
  time frame: Study Day 30
  description: TNF-α
  measure: Inflammatory Markers, hs-CRP
  time frame: Study Day 30
  description: hs-CRP
  measure: Inflammatory Markers,Serum ferritin
  time frame: Study Day 30
  description: Serum ferritin
  measure: Inflammatory Markers,D-dimer
  time frame: Study Day 30
  description: D-dimer
  measure: CD6 receptor expression levels
  time frame: Study Day 30
  description: Mean change of CD6 receptor expression levels in relative to baseline
  measure: T cell subsets
  time frame: Study Day 30
  description: Mean change of different T cell subsets in relative to baseline
  measure: The proportion of patients with stable or improved Lung Function
  time frame: Study Day 30
  description: Defined as patients with stable or improved PaO2 without increasing FiO2 in relative to baseline
  measure: Mean change from baseline in Murray Score
  time frame: Study Day 30
  description: Mean change of Murray Score in relative to baseline，The higher score means the worse outcome
  measure: Mean change from baseline in SOFA score
  time frame: Study Day 30
  description: Mean change of SOFA（Sequential Organ Failure Assessment） score in relative to baseline，The higher score means the worse outcome
  measure: Mechanical ventilation-free days
  time frame: Study Day 30
  description: Duration of non-Mechanical ventilation
  measure: Oxygen therapy-free days
  time frame: Study Day 30
  description: Duration of non-Oxygen therapy
  measure: Duration of ICU stay
  time frame: Study Day 30
  description: ICU stay days
  measure: Mortality rate
  time frame: Study Day 15, 30
  description: Defined as the proportion of patients who met fatal outcome event by Day 15 and 30
  measure: Clinical status assessed using a 7-category ordinal scale
  time frame: Study Day 30
  description: Clinical status assessed using a 7-category ordinal scale
  measure: Incidence of ADA
  time frame: Study Day 30
  description: Defined as the precentage of subjects presenting anti-drug antibody
  arm group label: Itolizumab Dose Level 1
  arm group type: Experimental
  description: Itolizumab of 50 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.
  arm group label: Itolizumab Dose Level 2
  arm group type: Experimental
  description: Itolizumab of 100 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.
  arm group label: Itolizumab Dose Level 3
  arm group type: Experimental
  description: Itolizumab of 150 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.
  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: Bin Du
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: Huadong Zhu
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: DANDAN Gao
  phone: 010-51571020
  email: gaodandan@biotechplc.com
  responsible party type: Sponsor
  mesh term: Respiratory Distress Syndrome
  mesh term: Respiratory Distress Syndrome, Newborn
  mesh term: Acute Lung Injury
  mesh term: Syndrome
  sharing ipd: No