Nontuberculous Mycobacterium Infection, Mycobacterium Abscessus Infection
Conditions
Keywords
NTM, MABC, MABC-PD, rapid growers
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
Interventions
DRUGDelpazolid
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.
Sponsors
LigaChem Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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 ≤ 8 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: 1. Patients who have been confirmed positive at least once in the last sputum or bronchoscopy sample culture performed prior to screening 2. 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: 1. Hemoglobin \> 9.0 g/dL (without transfusion within 2 weeks prior to measurement) 2. Absolute neutrophil count ≥ 1,500/µL (without administration of G-CSF within 2 weeks prior to measurement) 3. Platelet ≥ 100,000/µL 4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) 5. Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 × ULN 6. 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 NTM 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 has received linezolid for MABC treatment within 3 months prior to screening * 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 1. Patients with severe cardiac failure (New York Heart Association \[NYHA\] class III/IV) that occurred within 24 weeks prior to screening 2. 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 1. Administration of a new antibacterial agent for the prioritized treatment of NTM, especially MABC, other than background therapy 2. Monoamine oxidase inhibitors 3. Serotonin reuptake inhibitor or serotonin 5-HT1 receptor agonists 4. Meperidine or buspirone 5. Drugs that lower epilepsy threshold; tramadol, etc. 6. Tricyclic Antidepressant 7. Other investigational products: If there is a history of administration within 30 days prior to screening, it falls under the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| semi-quantitative scale (SQS) change versus baseline | 12 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Sputum culture conversion rate | 12 weeks | neg culture x3( sputum conversion) |
| Time to culture conversion | 12 weeks | from the date of assignment to the first negative result. |
| Time to positivity in the liquid culture automated system (MGIT) | 12 weeks | time to detection of positive in MGIT system |
| Negative sputum culture rate at each time point after baseline | 12 weeks | negative culture results in MGIT and solid media |
| Change from baseline in SQS | 4 weeks and 8 weeks | The SQS using liquid media and solid media will be scored a point of 1-7, with lower scores representing a reducing bacterial load. |
| Change from baseline in the CT score | 12 weeks | The CT scan score will be transformed onto a scale of 0-42, with lower scores representing improved lung presentations. Descriptive statistics for each point in time are presented, and intra-group comparison of CT score changes at 12 weeks compared to baseline |
| Quality of Life Questionnaire-Bronchiectasis | 12 weeks | 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 | 12 weeks | Six-minute walk test |
| Extended administration | After 12 weeks | 1\) SQS at each time point compared to baseline in subjects receiving extended administration * The SQS using liquid media and solid media will be scored a point of 1-7, with lower scores representing a reducing bacterial load 2) Inflammatory markers at each time point compared to baseline in subjects receiving extended administration * erythrocyte sedimentation rate 3) CT scores at each time point compared to baseline in subjects receiving extended administration * The CT scan score will be transformed onto a scale of 0-42, with lower scores representing improved lung presentations. 4\) QOL-B change at each time point compared to baseline in subjects receiving extended administration * The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life. 5\) sputum culture negative conversion at each time point compared to baseline in subjects receiving extended administration * negative culture results in MGIT and solid media |
| Change from baseline in the inflammatory marker | 12 weeks | erythrocyte sedimentation rate \[ESR\]) at each time point |
Countries
South Korea
Outcome results
None listed