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Safety and Preliminary Clinical Activity of Itolizumab in ARDS

Primary Purpose

Acute Respiratory Distress Syndrome

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Itolizumab
Sponsored by
Biotech Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female subject aged 18-75 years old (inclusive) Clinical diagnosis with infectious pneumonia as determined by the investigator Subject who havd received anti-infective treatment according to clinical practice. Diagnosis with ARDS according to the following criteria: (i) Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules; (ii) respiratory failure not fully explained by cardiac failure or fluid overload; (iii) Oxygenation (PaO2/FiO2) ≤300. ARDS diagnosed within 48 hours before administration, and fullfil the criteria of ARDS before administration Fullfill at least 2 of the following 4 criteria: ① elevated hs-CRP (>6 ULN); ② elevated IL-6 (>3 ULN); ③ high serum ferritin (>500µg/L at any one time or more than 2-fold increase within 48 hours of onset); ④ high D-dimer (>3 ULN). Negative result of serum HCG within 72 hours before enrollment for female with potential fertility Participant or his/her legal representive (when the participant is not capable of giving consent) is able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF) Exclusion Criteria: ARDS caused by non-infectious pneumonia (e.g., burns, drowning, poisoning, etc.) Subject who has cardiogenic pulmonary edema, and it is the main cause of respiratory failure Subject who is at high risk of death within 24 hours regardless of the treatment measures given as determined by the investigator Subject who is receiving extracorporeal membrane pulmonary oxygenation (ECMO) therapy at the time of screening. Subject who had received mechanical ventilation for more than 72 hours prior to administration. Subject with active tumors (other than carcinoma in situ or basal cell carcinoma) that requiring treatment. Any of the following chronic organ damage or immunosuppression: Cardiac: cardiac arrest within 7 days prior to screening; New York Heart Association cardiac function class IV at screening; Pulmonary: oxygen therapy or ventilator-dependent therapy for more than 1 month cumulatively within 6 months prior to screening; pulmonary embolism within 4 weeks prior to screening; pulmonary hypertension, end-stage lung disease, or interstitial lung disease requiring glucocorticoid therapy at screening; Renal: serum creatinine > 1.5 ULN or creatinine clearance < 30 mL/min at screening (Cockcroft-Gault formula, see study protocol annex 5 for details) or on long-term dialysis treatment; Liver: liver function classification of Child-Pugh grade C at screening; Immunosuppression status: with lymphoma, leukemia or acquired immunodeficiency; having received antitumor chemotherapy in the last 3 months, or being treated with immunosuppression for organ transplantation or immune disorders; having had allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation. Subject who had vaccination within 28 days prior to administration, or plan to get the vaccine during the study period Any of the following abnormalities at screening Hepatitis B-related tests: ① positive for hepatitis B surface antigen (HBsAg); ② positive for hepatitis B core antibody (HBcAb); ③ positive for hepatitis B surface antibody (HBsAb) and no history of hepatitis B vaccination; ④ positive for hepatitis B e antigen or hepatitis B e antibody; Positive hepatitis C virus antibody (HCV-Ab); Positive acquired immunodeficiency syndrome antibody (HIV-Ab). Subject who has a medical history of tuberculosis or those who deny a history of tuberculosis but has a positive gamma-interferon release test at screening. Absolute lymphocyte count < 0.2×109/L at screening Suspected allergic to the investigational drug or any of its excipients Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment Subject who had participated in other clinical studies (other than those not receiving interventions, such as observational study or questionnaires survey) within 3 months prior to screening, or who are participating in other experimental treatments. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Itolizumab Dose Level 1

    Itolizumab Dose Level 2

    Itolizumab Dose Level 3

    Arm 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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Incidence of Treatment Emergent Adverse Events
    Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0

    Secondary Outcome Measures

    Maximum serum concentration of Itolizumab, Cmax
    Maximum serum concentration of Itolizumab
    Minimum serum concentration of Itolizumab, Cmin
    Minimum serum concentration of Itolizumab
    Time to maximum serum concentration of Itolizumab, Tmax
    Time to maximum serum concentration of Itolizumab
    Total Itolizumab exposure across time, AUC0-t
    Total Itolizumab exposure across time
    Half life of Itolizumab, t1/2
    Half life of Itolizumab
    Inflammatory Markers,IL-6
    IL-6
    Inflammatory Markers,TNF-α
    TNF-α
    Inflammatory Markers, hs-CRP
    hs-CRP
    Inflammatory Markers,Serum ferritin
    Serum ferritin
    Inflammatory Markers,D-dimer
    D-dimer
    CD6 receptor expression levels
    Mean change of CD6 receptor expression levels in relative to baseline
    T cell subsets
    Mean change of different T cell subsets in relative to baseline
    The proportion of patients with stable or improved Lung Function
    Defined as patients with stable or improved PaO2 without increasing FiO2 in relative to baseline
    Mean change from baseline in Murray Score
    Mean change of Murray Score in relative to baseline,The higher score means the worse outcome
    Mean change from baseline in SOFA score
    Mean change of SOFA(Sequential Organ Failure Assessment) score in relative to baseline,The higher score means the worse outcome
    Mechanical ventilation-free days
    Duration of non-Mechanical ventilation
    Oxygen therapy-free days
    Duration of non-Oxygen therapy
    Duration of ICU stay
    ICU stay days
    Mortality rate
    Defined as the proportion of patients who met fatal outcome event by Day 15 and 30
    Clinical status assessed using a 7-category ordinal scale
    Clinical status assessed using a 7-category ordinal scale
    Incidence of ADA
    Defined as the precentage of subjects presenting anti-drug antibody

    Full Information

    First Posted
    July 20, 2023
    Last Updated
    August 3, 2023
    Sponsor
    Biotech Pharmaceutical Co., Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05978544
    Brief Title
    Safety and Preliminary Clinical Activity of Itolizumab in ARDS
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 31, 2023 (Anticipated)
    Primary Completion Date
    November 30, 2025 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Biotech Pharmaceutical Co., Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    To evaluate the safety, tolerability, PK, PD, and clinical activity of Itolizumab in subjects with acute respiratory distress syndrome (ARDS) caused by Infectious Pneumonia.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Respiratory Distress Syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    38 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Itolizumab Dose Level 1
    Arm Type
    Experimental
    Arm 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 Title
    Itolizumab Dose Level 2
    Arm Type
    Experimental
    Arm 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 Title
    Itolizumab Dose Level 3
    Arm Type
    Experimental
    Arm 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(s)
    Itolizumab
    Other Intervention Name(s)
    T1h
    Intervention Description
    Patients to be treated with Itolizumab.
    Primary Outcome Measure Information:
    Title
    Incidence of Treatment Emergent Adverse Events
    Description
    Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0
    Time Frame
    Study Day 58
    Secondary Outcome Measure Information:
    Title
    Maximum serum concentration of Itolizumab, Cmax
    Description
    Maximum serum concentration of Itolizumab
    Time Frame
    Study Day 30
    Title
    Minimum serum concentration of Itolizumab, Cmin
    Description
    Minimum serum concentration of Itolizumab
    Time Frame
    Study Day 30
    Title
    Time to maximum serum concentration of Itolizumab, Tmax
    Description
    Time to maximum serum concentration of Itolizumab
    Time Frame
    Study Day 30
    Title
    Total Itolizumab exposure across time, AUC0-t
    Description
    Total Itolizumab exposure across time
    Time Frame
    Study Day 30
    Title
    Half life of Itolizumab, t1/2
    Description
    Half life of Itolizumab
    Time Frame
    Study Day 30
    Title
    Inflammatory Markers,IL-6
    Description
    IL-6
    Time Frame
    Study Day 30
    Title
    Inflammatory Markers,TNF-α
    Description
    TNF-α
    Time Frame
    Study Day 30
    Title
    Inflammatory Markers, hs-CRP
    Description
    hs-CRP
    Time Frame
    Study Day 30
    Title
    Inflammatory Markers,Serum ferritin
    Description
    Serum ferritin
    Time Frame
    Study Day 30
    Title
    Inflammatory Markers,D-dimer
    Description
    D-dimer
    Time Frame
    Study Day 30
    Title
    CD6 receptor expression levels
    Description
    Mean change of CD6 receptor expression levels in relative to baseline
    Time Frame
    Study Day 30
    Title
    T cell subsets
    Description
    Mean change of different T cell subsets in relative to baseline
    Time Frame
    Study Day 30
    Title
    The proportion of patients with stable or improved Lung Function
    Description
    Defined as patients with stable or improved PaO2 without increasing FiO2 in relative to baseline
    Time Frame
    Study Day 30
    Title
    Mean change from baseline in Murray Score
    Description
    Mean change of Murray Score in relative to baseline,The higher score means the worse outcome
    Time Frame
    Study Day 30
    Title
    Mean change from baseline in SOFA score
    Description
    Mean change of SOFA(Sequential Organ Failure Assessment) score in relative to baseline,The higher score means the worse outcome
    Time Frame
    Study Day 30
    Title
    Mechanical ventilation-free days
    Description
    Duration of non-Mechanical ventilation
    Time Frame
    Study Day 30
    Title
    Oxygen therapy-free days
    Description
    Duration of non-Oxygen therapy
    Time Frame
    Study Day 30
    Title
    Duration of ICU stay
    Description
    ICU stay days
    Time Frame
    Study Day 30
    Title
    Mortality rate
    Description
    Defined as the proportion of patients who met fatal outcome event by Day 15 and 30
    Time Frame
    Study Day 15, 30
    Title
    Clinical status assessed using a 7-category ordinal scale
    Description
    Clinical status assessed using a 7-category ordinal scale
    Time Frame
    Study Day 30
    Title
    Incidence of ADA
    Description
    Defined as the precentage of subjects presenting anti-drug antibody
    Time Frame
    Study Day 30

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female subject aged 18-75 years old (inclusive) Clinical diagnosis with infectious pneumonia as determined by the investigator Subject who havd received anti-infective treatment according to clinical practice. Diagnosis with ARDS according to the following criteria: (i) Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules; (ii) respiratory failure not fully explained by cardiac failure or fluid overload; (iii) Oxygenation (PaO2/FiO2) ≤300. ARDS diagnosed within 48 hours before administration, and fullfil the criteria of ARDS before administration Fullfill at least 2 of the following 4 criteria: ① elevated hs-CRP (>6 ULN); ② elevated IL-6 (>3 ULN); ③ high serum ferritin (>500µg/L at any one time or more than 2-fold increase within 48 hours of onset); ④ high D-dimer (>3 ULN). Negative result of serum HCG within 72 hours before enrollment for female with potential fertility Participant or his/her legal representive (when the participant is not capable of giving consent) is able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF) Exclusion Criteria: ARDS caused by non-infectious pneumonia (e.g., burns, drowning, poisoning, etc.) Subject who has cardiogenic pulmonary edema, and it is the main cause of respiratory failure Subject who is at high risk of death within 24 hours regardless of the treatment measures given as determined by the investigator Subject who is receiving extracorporeal membrane pulmonary oxygenation (ECMO) therapy at the time of screening. Subject who had received mechanical ventilation for more than 72 hours prior to administration. Subject with active tumors (other than carcinoma in situ or basal cell carcinoma) that requiring treatment. Any of the following chronic organ damage or immunosuppression: Cardiac: cardiac arrest within 7 days prior to screening; New York Heart Association cardiac function class IV at screening; Pulmonary: oxygen therapy or ventilator-dependent therapy for more than 1 month cumulatively within 6 months prior to screening; pulmonary embolism within 4 weeks prior to screening; pulmonary hypertension, end-stage lung disease, or interstitial lung disease requiring glucocorticoid therapy at screening; Renal: serum creatinine > 1.5 ULN or creatinine clearance < 30 mL/min at screening (Cockcroft-Gault formula, see study protocol annex 5 for details) or on long-term dialysis treatment; Liver: liver function classification of Child-Pugh grade C at screening; Immunosuppression status: with lymphoma, leukemia or acquired immunodeficiency; having received antitumor chemotherapy in the last 3 months, or being treated with immunosuppression for organ transplantation or immune disorders; having had allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation. Subject who had vaccination within 28 days prior to administration, or plan to get the vaccine during the study period Any of the following abnormalities at screening Hepatitis B-related tests: ① positive for hepatitis B surface antigen (HBsAg); ② positive for hepatitis B core antibody (HBcAb); ③ positive for hepatitis B surface antibody (HBsAb) and no history of hepatitis B vaccination; ④ positive for hepatitis B e antigen or hepatitis B e antibody; Positive hepatitis C virus antibody (HCV-Ab); Positive acquired immunodeficiency syndrome antibody (HIV-Ab). Subject who has a medical history of tuberculosis or those who deny a history of tuberculosis but has a positive gamma-interferon release test at screening. Absolute lymphocyte count < 0.2×109/L at screening Suspected allergic to the investigational drug or any of its excipients Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment Subject who had participated in other clinical studies (other than those not receiving interventions, such as observational study or questionnaires survey) within 3 months prior to screening, or who are participating in other experimental treatments. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    DANDAN Gao
    Phone
    010-51571020
    Email
    gaodandan@biotechplc.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bin Du
    Organizational Affiliation
    Peking Union Medical College Hospital
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Huadong Zhu
    Organizational Affiliation
    Peking Union Medical College Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Safety and Preliminary Clinical Activity of Itolizumab in ARDS

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