萝莉社

The purpose of this study is to find out if a new investigational drug called Clofazimine Inhalation Suspension can help treat people with NTM lung disease.聽 Part A of the study is made up of two cycles, Cycle 1 and Cycle 2. During each Cycle, you will dose with either Clofazimine Inhalation Suspension or placebo for 28 days in a row. You will then be off Clofazimine Inhalation Suspension or placebo for 56 days in a row. The duration of Part A Cycles 1 and 2 will be approximately 6 months.聽 During this entire time on and off study treatment during Part A, you will continue with your current treatment for NTM lung disease, as prescribed and managed by your healthcare provider. After you complete the study treatment in Part A, you will be eligible to receive Clofazimine Inhalation Suspension in Part B. The duration of Part B will be based on your sputum culture conversion, which can be up to an additional 18 months if your sputum cultures do not convert early on to negative.

Inclusion

Evidence of signed and dated informed consent document(s) indicating that the participant has been informed of all pertinent aspects of the trial. Age 鈮�18 years and 鈮�85 years at screening. Evidence of underlying nodular bronchiectasis and/or fibrocavitary disease on a chest radiograph or chest computed tomography, as determined by the investigator, within the 12 months prior to screening. MAC-positive culture results from at least two separate (at least 1 week apart) sputum samples, one taken within 12 months, and another taken within 3 months prior to the date of informed consent. The most recent sputum culture with available results should be expectorated (e.g., not collected via bronchoscopy) and positive for MAC. The time windows are based on the dates the samples are taken, not the dates of analysis or reporting. Note: A sputum culture will be obtained at baseline, but the participant may be randomized prior to availability of the results. (Co-infection with another NTM species including M. abscessus is allowed; see Section 5.4).

Be able to produce at least 3 mL of sputum or be willing to undergo an induction that produces at least 3 mL of sputum for mycobacteriology. FEV1 鈮�40% of predicted during screening, as calculated by the local spirometry laboratory standards. Currently receiving a multi-drug regimen of GBT for pulmonary NTM infection in line with the 2020 ATS/ERS/ESCMID/IDSA guideline for the treatment of NTM pulmonary disease for at least 6 months prior to consenting to participate in this study, with no changes in this regimen within 2 months of screening. For female participants of childbearing potential, a negative serum pregnancy test and agreement to use a protocol-recommended method of contraception during heterosexual intercourse from the start of the screening period until 鈮�12 months after the final dose of study therapy. For male participants who can father a child and are having intercourse with females of childbearing potential, agreement to use a protocol-recommended method of contraception from the start of the study therapy until 鈮�12 months after the final dose of the study therapy and to refrain from sperm donation from the start of study therapy until 鈮�12 months after administration of the final dose of study therapy.

Willingness and ability to comply with scheduled visits, drug inhalation plan, study procedures, laboratory tests, and study restrictions. Participants who have co-infection with another NTM species in addition to MAC. Participants who have co-infection with another NTM species in addition to MAC, the MAC should be the predominant NTM species assessed by the investigator based on the clinical judgment of the investigator

Exclusion

Clinical diagnosis of cystic fibrosis. Active tuberculosis Disseminated MAC or MABSC infection or participants with isolated MABSC infection.

1. Recent (i.e., within the last 3 months from date of screening) ICU admission with or without mechanical ventilation. Inability to inhale with a nebulizer, in the opinion of the investigator. Participants with known hypersensitivity to any of the ingredients or excipients of clofazimine. Prior therapy with clofazimine in the previous 4 months from date of screening. Participants with known resistance to clofazimine as treatment for MAC
2. Prior therapy with amikacin by any route of administration (e.g., inhaled or IV) in the previous 2 months from date of screening. Ongoing participation in any other interventional drug or device clinical trial, or exposure to another investigational drug or device within 28 days prior to start of study treatment. Current (or planned during the study) pregnancy or breastfeeding. QT prolongation during screening (450 ms or longer), and/or uncontrolled sinus rhythm (>110/minute). Increased risk for proarrhythmia A family history of sudden cardiac death, unexplained death, long-QT syndrome, or death from a primary dysrhythmia potentially associated with QT prolongation. Recent (within 4 months) initiation of or increase in the dosing regimen of any concomitant medication that is known to prolong the QT interval. Chronic and clinically meaningful, in the opinion of the investigator, abnormalities in potassium, magnesium, or calcium levels. Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within 3 years before screening or anticipated during the study period. Current alcohol, medication, or illicit drug abuse, per the investigator's clinical judgment. Prior or ongoing social or medical condition (e.g., concomitant illness, psychiatric condition, behavioral disorder), medical history, physical findings, ECG findings, or laboratory abnormality that, in the opinion of the investigator, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. Any prior use of bedaquiline within 1 year of screening. ALT or AST >1.5 times ULN or total bilirubin >1.5 times ULN during screening. Absolute neutrophil count