Clinical trial NCT06004037: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nontuberculous Mycobacterium Infection
Mycobacterium Abscessus Infection
Keywords: NTM
MABC
MABC-PD
rapid growers
Lead sponsor: LigaChem Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-22
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 ≤ 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 exclusion criteria.
* Pregnant or breastfeeding women and women of childbearing potential who do not agree to practice appropriate contraceptive methods\*:

Primary outcomes:
measure: semi-quantitative scale (SQS) change versus baseline
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline in SQS
timeFrame: 4 weeks and 8 weeks
measure: Sputum culture conversion rate
timeFrame: 12 weeks
measure: Time to culture conversion
timeFrame: 12 weeks
measure: Time to positivity in the liquid culture automated system (MGIT)
timeFrame: 12 weeks
measure: Negative sputum culture rate at each time point after baseline
timeFrame: 12 weeks
measure: Change from baseline in the inflammatory marker
timeFrame: 12 weeks
measure: Change from baseline in the CT score
timeFrame: 12 weeks
measure: Quality of Life Questionnaire-Bronchiectasis
timeFrame: 12 weeks
measure: Six-minute walk test
timeFrame: 12 weeks
measure: Extended administration
timeFrame: After 12 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Bundang Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
References: