MannKind Corporation has announced the initiation of its Phase 3 clinical trial, ICoN-1, designed to evaluate the efficacy and safety of Clofazimine Inhalation Suspension for the treatment of nontuberculous mycobacterial (NTM) lung disease. The first site has been activated in Australia, marking a significant step forward in addressing this challenging condition.
The ICoN-1 study is a multi-national, randomized, double-blind, placebo-controlled trial that will enroll approximately 230 participants at over 100 sites globally. The trial has received clearance from regulatory authorities in Australia, the United States, Japan, and South Korea, with approval in Taiwan expected by the end of the year. The first participant was randomized in September.
"With our first site initiation visit (SIV) and regulatory approvals to date in Australia, we are looking forward to enrolling patients for the ICoN-1 study in an effort to further develop a potential therapy for those living with serious NTM lung infections," said Dr. Burkhard Blank, Executive Vice President, Research & Development and Chief Medical Officer for MannKind Corporation.
Trial Design and Endpoints
The ICoN-1 trial focuses on adults with refractory NTM lung disease caused by mycobacterium avium complex (MAC). Participants will receive Clofazimine Inhalation Suspension in addition to guideline-based therapy, followed by an open-label extension. The primary endpoint is sputum culture conversion (negative for NTM) from baseline to the end of Month 6. In the U.S., a co-primary endpoint will assess changes in quality of life (QoL) during the same period.
Regulatory Designations and Intellectual Property
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Clofazimine Inhalation Suspension (MNKD-101) for the treatment of NTM lung disease. The FDA has also previously designated it as both an orphan drug and a qualified infectious disease product (QIDP) for this indication. Clofazimine Inhalation Suspension holds a patent (No. 11,793,808) valid until June 8, 2039, covering compositions of clofazimine and methods for treating lung infections. Similar patent protection exists in Japan (7377259), with applications pending in Australia and other countries.
NTM Lung Disease: An Unmet Medical Need
Pulmonary NTM infection is a rare disease with increasing global prevalence. It is associated with shortened lifespan, high morbidity, and significant impact on patients’ quality of life. NTM comprises a group of bacteria found in the environment that can cause cough, fatigue, reduced lung function, and other debilitating symptoms. Individuals with underlying conditions like COPD, asthma, and bronchiectasis are at higher risk. MAC accounts for approximately 80% of NTM lung disease cases in the United States. Approximately 15-20% of NTM patients are refractory. Estimated 2022 NTM disease prevalence is more than 100,000 in the U.S. and over 150,000 in Japan. The prevalence rate of NTM is increasing globally, with claims-based studies suggesting an annual rise of 7.5% within the U.S.
