RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex Disease

A 2-part multi-center, Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of RHB-204 in adult subjects with underlying nodular bronchiectasis and documented MAC lung infection.

The co-primary efficacy endpoints at the end of Part 1 evaluate the proportion of patients with sputum culture conversion after 6 months of treatment defined as three consecutive monthly negative sputum cultures at Months 4, 5, and 6 for RHB-204 compared to placebo and the mean change in the Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo.

At the Month 6 visit (end of Part 1), after all assessments including questionnaires and sputum samples have been collected, subjects will enter Part 2 of the study and receive open-label RHB-204.

In order to comply with current treatment duration guidelines (Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium avium Complex: Developing Drugs for Treatment - FDA Draft Guidance September 2021) in this protocol subjects will receive active treatment for 12 months after sputum culture conversion. As such, each subject's first negative culture that defines conversion will determine the total duration of their active study drug treatment. The longest duration of active study drug treatment will be 16 months. At the end of study treatment, all subjects will enter a 3-month post-treatment follow-up period (see study design section below for additional details).

To maintain the blind and integrity of the data, an independent team (Sputum Culture Monitors) will inform sites on each subject's treatment duration based on sputum culture conversion. Sputum Culture Monitors will also have access to randomized treatment allocation. All other study related personnel will remain blinded to sputum culture results and treatment allocation (Sponsor, CRO, medical monitors, safety, ECG and sputum laboratories, site personnel as well as participating subjects).

During Part 1, subjects who have completed at least the first 3 months of treatment with study drug, and at the Investigator's discretion, require rescue therapy (alternative anti-NTM treatment) will discontinue study drug (performing an EOT visit) and remain in the study to complete all scheduled study visits and assessments/procedures to Month 6 (performing an EOS visit).

Subjects who complete treatment based on the timeline provided by the Sputum Culture Monitors (EOT visit) and have an ongoing negative sputum culture will be reconsented to enter a follow-up Extension Study, to evaluate sputum culture results at two (2) further time points: 6 months and 12 months following end of treatment (EOT) for each subject in protocol RHB-204-01.