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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Nontuberculous Mycobacterium Infection, Mycobacterium Abscessus Infection

Intervention / Treatment
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* Drug: Delpazolid


Participation Criteria
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Eligibility Criteria
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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*:

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: delpazolid<br>In addition to background therapy for MABC, patients will be given orally three tablets (400 mg/tablet) of LCB01-0371 for 12 weeks. | Drug: Delpazolid<br>* 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.<br>* Other names: LCB01-0371;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks and 8 weeks | 
| Sputum culture conversion rate | neg culture x3( sputum conversion) | 12 weeks | 
| Time to culture conversion | from the date of assignment to the first negative result. | 12 weeks | 
| Time to positivity in the liquid culture automated system (MGIT) | time to detection of positive in MGIT system | 12 weeks | 
| Negative sputum culture rate at each time point after baseline | negative culture results in MGIT and solid media | 12 weeks | 
| Change from baseline in the inflammatory marker | erythrocyte sedimentation rate [ESR]) at each time point | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| Six-minute walk test | Six-minute walk test | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NTM, MABC, MABC-PD, rapid growers