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Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex

Primary Purpose

Nontuberculous Mycobacterium Infection, Mycobacterium Abscessus Infection

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Delpazolid
Sponsored by
LegoChem Biosciences, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nontuberculous Mycobacterium Infection focused on measuring NTM, MABC, MABC-PD, rapid growers

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Pre-screening: Adults aged 19 years or above Pre-screening: Patients diagnosed with MABC (including subspecies abscessus, bolletii, and massiliense) pulmonary disease in radiologic and microbiologic evaluations LCB01-0371 MIC ≤ 4 μg/mL for MABC Patients who continue to show positivity for MABC even after treatments based on the guidelines of ATS/ERS/ESCMID/IDSA for at least 6 months prior to screening, and who meet all of the following criteria: Patients who have been confirmed positive at least once in the last sputum or bronchoscopy sample culture performed prior to screening Patients who have not achieved culture conversion (at least 3 consecutive negative mycobacteria cultures in the sputum or bronchoscopy sample collected at an interval of at least 4 weeks) within 6 months prior to screening Patients who can voluntarily expectorate sputum at screening Patients with a life expectancy of 12 weeks or more Patients with adequate organ function who meet the following criteria: Hemoglobin > 9.0 g/dL (without transfusion within 2 weeks prior to measurement) Absolute neutrophil count ≥ 1,500/µL (without administration of G-CSF within 2 weeks prior to measurement) Platelet ≥ 100,000/µL Total bilirubin ≤ 1.5 × upper limit of normal (ULN) Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance >30 mL/min (calculated with the Cockcroft-Gault formula) Patients who voluntarily provided a written consent to participate in the clinical study Exclusion Criteria: Patients who cannot swallow the study drug tablet due to dysphagia, nasogastric tube insertion, etc. Patients diagnosed with cystic fibrosis Patients who have received a lung transplant Patients with disseminated or extrapulmonary nontuberculous mycobacteria Patients with known active pulmonary tuberculosis Patients with atypical mycobacterial infections other than MABC Patients with an active pulmonary malignancy within 1 year prior to screening or Patients with other malignancies that require chemotherapy or radiotherapy Patients who were administered linezolid for more than 2 weeks to treat MABC Patients with known HIV positivity or a suspected infection thereof or Patients with a known active hepatitis B or C infection Patients who currently have a clinically significant cardiovascular disease Patients with severe cardiac failure (New York Heart Association [NYHA] class III/IV) that occurred within 24 weeks prior to screening Patients with pulmonary embolism or deep venous thrombosis that occurred within 24 weeks prior to screening Patients whose multidrug therapy for treatment of MABC was changed within 4 weeks prior to screening (Discontinuation, dose adjustment, change of administration route, etc., are allowed.) Patients for whom the administration of contraindicated concomitant drugs that correspond to the following cannot be discontinued during the clinical study or for whom their administration is necessary Administration of a new antibacterial agent for the prioritized treatment of atypical mycobacteria, especially MABC, other than background therapy Monoamine oxidase inhibitors Serotonin reuptake inhibitor or serotonin 5-HT1 receptor agonists Meperidine or buspirone Drugs that lower epilepsy threshold; tramadol, etc. Other investigational products: If there is a history of administration within 30 days prior to screening, it falls under the exclusion criteria. Pregnant or breastfeeding women and women of childbearing potential who do not agree to practice appropriate contraceptive methods*:

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    delpazolid

    Arm Description

    In addition to background therapy for MABC, patients will be given orally three tablets (400 mg/tablet) of LCB01-0371 for 12 weeks.

    Outcomes

    Primary Outcome Measures

    Change from baseline in the semi-quantitative scale (SQS)
    The SQS using liquid media and solid media will be scored a point of 1-7, with lower scores representing a reducing bacterial load.

    Secondary Outcome Measures

    Change from baseline in SQS
    The SQS using liquid media and solid media will be scored a point of 1-7, with lower scores representing a reducing bacterial load.
    Sputum culture conversion rate
    neg culture x3( sputum conversion)
    Time to culture conversion
    from the date of assignment to the first negative result.
    Time to positivity in the liquid culture automated system (MGIT)
    time to detection of positive in MGIT system
    Negative sputum culture rate at each time point after baseline
    negative culture results in MGIT and solid media
    Change from baseline in the inflammatory marker
    erythrocyte sedimentation rate [ESR]) at each time point
    Change from baseline in the CT score
    The CT scan score will be transformed onto a scale of 0-42, with lower scores representing improved lung presentations.
    Quality of Life Questionnaire-Bronchiectasis
    The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.
    Six-minute walk test
    Six-minute walk test

    Full Information

    First Posted
    August 16, 2023
    Last Updated
    August 21, 2023
    Sponsor
    LegoChem Biosciences, Inc
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06004037
    Brief Title
    Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex
    Official Title
    A Phase 2a, Open-label, Single-arm, Multi-center Study to Evaluate the Efficacy and Safety of LCB01-0371 (Delpazolid) as Add-on Therapy in Patients With Refractory Mycobacterium Abscessus Complex Pulmonary Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2023 (Anticipated)
    Primary Completion Date
    July 29, 2025 (Anticipated)
    Study Completion Date
    May 29, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    LegoChem Biosciences, Inc

    4. Oversight

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

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the efficacy and safety of delpazolid add-on therapy in Patients with Refractory Mycobacterium abscessus Complex Pulmonary disease
    Detailed Description
    Delpazolid, which demonstrates effects similar to other oxazolidinone-class drugs and has confirmed good safety, aims to evaluate its efficacy in MABC-PD patients who are unresponsive to guideline-based treatments

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Nontuberculous Mycobacterium Infection, Mycobacterium Abscessus Infection
    Keywords
    NTM, MABC, MABC-PD, rapid growers

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    delpazolid
    Arm Type
    Experimental
    Arm Description
    In addition to background therapy for MABC, patients will be given orally three tablets (400 mg/tablet) of LCB01-0371 for 12 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Delpazolid
    Other Intervention Name(s)
    LCB01-0371
    Intervention Description
    Three tablets (400 mg/tablet) of delpazolid will be orally administered once daily for 12 weeks. After 3 months (12 weeks) of administration, if the investigator determines that there are clinical benefits, an additional extended treatment of up to 9 months (40 weeks) may be given, amounting to 1 year of treatment in total.
    Primary Outcome Measure Information:
    Title
    Change from baseline in the semi-quantitative scale (SQS)
    Description
    The SQS using liquid media and solid media will be scored a point of 1-7, with lower scores representing a reducing bacterial load.
    Time Frame
    12 weeks
    Secondary Outcome Measure Information:
    Title
    Change from baseline in SQS
    Description
    The SQS using liquid media and solid media will be scored a point of 1-7, with lower scores representing a reducing bacterial load.
    Time Frame
    4 weeks and 8 weeks
    Title
    Sputum culture conversion rate
    Description
    neg culture x3( sputum conversion)
    Time Frame
    12 weeks
    Title
    Time to culture conversion
    Description
    from the date of assignment to the first negative result.
    Time Frame
    12 weeks
    Title
    Time to positivity in the liquid culture automated system (MGIT)
    Description
    time to detection of positive in MGIT system
    Time Frame
    12 weeks
    Title
    Negative sputum culture rate at each time point after baseline
    Description
    negative culture results in MGIT and solid media
    Time Frame
    12 weeks
    Title
    Change from baseline in the inflammatory marker
    Description
    erythrocyte sedimentation rate [ESR]) at each time point
    Time Frame
    12 weeks
    Title
    Change from baseline in the CT score
    Description
    The CT scan score will be transformed onto a scale of 0-42, with lower scores representing improved lung presentations.
    Time Frame
    12 weeks
    Title
    Quality of Life Questionnaire-Bronchiectasis
    Description
    The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.
    Time Frame
    12 weeks
    Title
    Six-minute walk test
    Description
    Six-minute walk test
    Time Frame
    12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    19 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Pre-screening: Adults aged 19 years or above Pre-screening: Patients diagnosed with MABC (including subspecies abscessus, bolletii, and massiliense) pulmonary disease in radiologic and microbiologic evaluations LCB01-0371 MIC ≤ 4 μg/mL for MABC Patients who continue to show positivity for MABC even after treatments based on the guidelines of ATS/ERS/ESCMID/IDSA for at least 6 months prior to screening, and who meet all of the following criteria: Patients who have been confirmed positive at least once in the last sputum or bronchoscopy sample culture performed prior to screening Patients who have not achieved culture conversion (at least 3 consecutive negative mycobacteria cultures in the sputum or bronchoscopy sample collected at an interval of at least 4 weeks) within 6 months prior to screening Patients who can voluntarily expectorate sputum at screening Patients with a life expectancy of 12 weeks or more Patients with adequate organ function who meet the following criteria: Hemoglobin > 9.0 g/dL (without transfusion within 2 weeks prior to measurement) Absolute neutrophil count ≥ 1,500/µL (without administration of G-CSF within 2 weeks prior to measurement) Platelet ≥ 100,000/µL Total bilirubin ≤ 1.5 × upper limit of normal (ULN) Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance >30 mL/min (calculated with the Cockcroft-Gault formula) Patients who voluntarily provided a written consent to participate in the clinical study Exclusion Criteria: Patients who cannot swallow the study drug tablet due to dysphagia, nasogastric tube insertion, etc. Patients diagnosed with cystic fibrosis Patients who have received a lung transplant Patients with disseminated or extrapulmonary nontuberculous mycobacteria Patients with known active pulmonary tuberculosis Patients with atypical mycobacterial infections other than MABC Patients with an active pulmonary malignancy within 1 year prior to screening or Patients with other malignancies that require chemotherapy or radiotherapy Patients who were administered linezolid for more than 2 weeks to treat MABC Patients with known HIV positivity or a suspected infection thereof or Patients with a known active hepatitis B or C infection Patients who currently have a clinically significant cardiovascular disease Patients with severe cardiac failure (New York Heart Association [NYHA] class III/IV) that occurred within 24 weeks prior to screening Patients with pulmonary embolism or deep venous thrombosis that occurred within 24 weeks prior to screening Patients whose multidrug therapy for treatment of MABC was changed within 4 weeks prior to screening (Discontinuation, dose adjustment, change of administration route, etc., are allowed.) Patients for whom the administration of contraindicated concomitant drugs that correspond to the following cannot be discontinued during the clinical study or for whom their administration is necessary Administration of a new antibacterial agent for the prioritized treatment of atypical mycobacteria, especially MABC, other than background therapy Monoamine oxidase inhibitors Serotonin reuptake inhibitor or serotonin 5-HT1 receptor agonists Meperidine or buspirone Drugs that lower epilepsy threshold; tramadol, etc. Other investigational products: If there is a history of administration within 30 days prior to screening, it falls under the exclusion criteria. Pregnant or breastfeeding women and women of childbearing potential who do not agree to practice appropriate contraceptive methods*:

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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