ICoN-1: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Efficacy and Safety of Treatment With MNKD-101 [Clofazimine Inhalation Suspension] When Added to Guideline-Based Therapy in Participants with Pulmonary Nontuberculous Mycobacterial Infection [Part A] Followed by an Open-Label Extension [Part B] (NCT06418711).

This clinical trial is designed to compare the efficacy and safety of Clofazimine Inhalation Suspension versus placebo when added to guideline-based therapy (GBT).

Trial phase

Phase 3

Trial participation type

This trial has been designed for the Clinical Research of a Drug.

Principal investigator

Prof C. Orla Morrissey

Key inclusion data

Inclusion: Evidence of underlying nodular bronchiectasis and/or fibrocavitary disease on a chest radiograph or chest computed tomography, as determined by the investigator, within the last 12 months; MAC-positive culture results from at least two separates (at least 1 week apart) expectorated sputum samples, one taken within 12 months, and another taken within 3 months prior to the date of informed consent; 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; 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 in this study, with no changes in this regimen within 2 months of screening; FEV1 ?40% of predicted during screening, as calculated by the local spirometry laboratory standards. Exclusion: Cystic fibrosis; Active tuberculosis; Disseminated MAC or MABSC infection or participants with isolated MABSC infection; Inability to inhale with a nebulizer, in the opinion of the investigator; Prior therapy with clofazimine in the previous 4 months from date of screening; Prior therapy with amikacin by any route of administration (e.g., inhaled or IV) in the previous 2 months from date of screening; QT prolongation during screening (450 ms or longer), and/or uncontrolled sinus rhythm (>110/minute); Increased risk of proarrhythmia (e.g., recent [within 6 months] myocardial infarction, stroke, heart failure decompensation or left ventricular ejection of <45%, ventricular arrhythmias, torsade de pointes, unstable angina, or high-degree atrioventricular block); Recent (within 6 months) initiation of or change 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; Any prior use of bedaquiline within 1 year of screening; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN during screening; Absolute neutrophil count <500/µL during screening; Use of prednisone ?10mg/day within 3 months prior to screening, or other significant immunosuppression as deemed by the investigator; Estimated glomerular filtration rate <30mL/minute/1.73 m2 (according to the CKD-EPI 2021 creatine equation) during screening; Advanced liver disease (Child-Pugh Class A, B, or C).