A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease

A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease

A Randomized, Double-Blinded, Placebo-Controlled, Multicenter, Phase 2, Dose-Ranging Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease

The purpose of the study is to evaluate The microbiological response and clinical efficacy of SPR720 compared with placebo in participants with nontuberculous mycobacteria pulmonary disease (NTM-PD). The safety and tolerability of SPR720 in a participants population with NTM- PD The pharmacokinetic (PK) of SPR719, active moiety, following orally (po) administered prodrug SPR720 in a participant population with NTM-PD.

Participants will receive SPR720 500 milligrams (mg) [250 mg × 2 capsules and 2 matching placebo capsules, orally QD for 56 days.

Slope of the Weekly Sputum Log10 Colony Forming Units Per Millilitre (CFU/mL) Change From Day 1 Through 56 in micro-Intent to Treat (m-ITT) Population

Slope of the Time to Positivity (TTP) using MGIT on Samples of Induced Sputum From Days 1 Through 56 (EOT) in micro-ITT Population

Susceptibility is ≥4-fold increase in minimum inhibitory concentration for same pathogen identified at Baseline.

Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened.

Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened.

Change From Baseline in 11-point Nontuberculous Mycobacteria Pulmonary Disease (NTM-PD) Symptoms and Impact Scale for Quality of Life (QOL) Assessments

The 11-point NTM-PD Symptoms and Impact Scale will evaluate specific clinical signs and symptoms and QOL improvements and will include symptoms of chronic cough, fatigue, frequent throat clearing, dyspnea, hemoptysis, excessive mucus (sputum) production, chills, night sweats, loss of appetite, unintended weight loss, wheezing, and chest pain.

Change From Baseline in 6-point Patient Global Impression of Severity (PGI-S) Scale for Quality of Life (QOL) Assessments

The PGI-S scale is comprised of a 6-point verbal descriptor scale to determine meaningful change reported for the other symptom ratings in participants with NTM-PD.

Change From Baseline in 7-point Patient Global Impression of Change (PGI-C) scale for Quality of Life (QOL) Assessments

Change From Baseline in Flu, COVID-19, or Other Illness Questionnaire (2 questions) for Quality of Life (QOL) Assessments

This 2-question form will assess the participants flu, COVID-19 or other illness status and how these illnesses have affected the participants NTM-PD disease over the past 7 days.

Change from Baseline in PROMIS® V1.0 Fatique Shortform 7a scale for Quality of Life (QOL) Assessments

The PROMIS® scale will assess the participants experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities using a validated 5-point Likert scale.

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational/experimental) product, whether related to this product or not.

Inclusion Criteria: Has a prior diagnosis of NTM-PD due to MAC Has at least one prior lower respiratory culture (sputum or bronchoalveolar lavage [BAL]) positive for MAC in the 12 months prior to consent Has an induced sputum culture at Screening positive for MAC by quantitative culture on solid agar Is either treatment naïve and has not received any prior treatment for MAC, OR if previously treated for MAC and meets all of the following criteria: Has a history of successful treatment with sputum culture conversion to negative Has recent sputum or BAL culture evidence of recurrent or relapsed disease and Has been off therapy for at least 3 months prior to consent Has clinical signs and symptoms within the 6 weeks prior to consent that are consistent with NTM-PD ≥2 of the following: chronic cough fatigue frequent throat clearing shortness of breath (dyspnea) coughing up of blood (hemoptysis) excessive mucus (sputum) production fever (temperature >38ºC or >100.4ºF) night sweats loss of appetite unintended weight loss wheezing chest pain Has a measured forced expiratory volume in the first second following maximal inhalation (FEV1) % predicted ≥30% within 3 months prior to consent. If prior FEV1% predicted test result is not available, obtain FEV1% predicted at Screening to confirm eligibility Exclusion Criteria: In the opinion of the Investigator, is not a candidate for a 4-month delay in initiation of standard multidrug therapy to participate in a placebo-controlled clinical trial (e.g., participant has severe symptoms or, extensive disease burden) Has disseminated or extrapulmonary NTM disease Has end-stage NTM-PD or treatment-refractory NTM-PD Has isolation on lower respiratory (sputum or BAL) cultures of any Mycobacterium species other than those included in MAC within the 6 months prior to consent Has any other condition or prior therapy, which, in the opinion of the Investigator, would make the participant unsuitable for this study, including compliance with all study assessments and adherence to the protocol schedule of assessment Prior exposure to SPR720. Participants who are unable to comply with the requirements of the study or who in the opinion of the Investigator should not participate in the study are not eligible Other inclusion and exclusion criteria as per protocol may apply.