Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Condition: Mycobacterium Avium Complex; Non-tuberculous Mycobacterium Pulmonary Disease
MeSH terms: Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; Lung Diseases
Intervention: SPR720; Placebo; Open-label Standard of Care
Intervention description: Capsules for oral administration; Capsules for oral administration; Standard of Care regimen is at the Investigator's discretion; recommended 2-drug or 3-drug SOC, consisting of either:
Clarithromycin 500-1000 mg, plus ethambutol hydrochloride (HCl) 15 mg/kg orally once daily or
Azithromycin 250-500 mg plus ethambutol HCl 15 mg/kg orally once daily.
Optional rifampin 600 mg or rifabutin 300 mg orally once daily may be added to the SOC regimen for up to 28 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To evaluate the pharmacokinetics (PK) of SPR719, the active moiety, generated from the orally
      (po) administered SPR720 prodrug in a patient population with nontuberculous mycobacteria
      pulmonary disease (NTM-PD)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a diagnosis of NTM-PD due to MAC

          -  Had at least 1 prior positive culture (sputum or bronchoalveolar lavage) positive for
             MAC in the previous 6 months

          -  Has an induced sputum culture at screening positive for MAC by at least one of the
             following methods performed by the microbiology laboratory: quantitative culture on
             solid agar or growth on liquid media (MGIT)

          -  Is either treatment naïve and has not received any prior treatment for MAC, OR if
             previously treated for MAC, has culture evidence of persistent, recurrent, or relapsed
             disease and has been off therapy for at least 6 months

          -  In the opinion of the Investigator, is ready to initiate treatment (treatment naïve)
             or reinitiate treatment (previously treated) within the next 3 months, and for whom a
             delay, in order to participate in a placebo-controlled clinical trial, is considered
             reasonable and clinically acceptable

          -  Had clinical signs and symptoms within the 6 weeks before the date of consent that are
             consistent with NTM-PD with at least two of the following:

               1. chronic cough

               2. fatigue

               3. frequent throat clearing

               4. shortness of breath (dyspnea)

               5. coughing up of blood (hemoptysis)

               6. excessive mucus (sputum) production

               7. fever

               8. night sweats

               9. loss of appetite

              10. unintended weight loss

              11. wheezing

              12. chest pain

          -  Has a measured forced expiratory volume in 1 second (% predicted FEV1) ≥30% on
             pulmonary function test within 3 months prior to consent

          -  Has a chest radiograph (CXR) or computed tomography (CT) scan within 6 months prior to
             consent with findings consistent with NTM-PD. If no CXR or CT scan is available, a CXR
             or CT scan should be performed at screening to confirm eligibility.

          -  Other inclusion criteria per protocol

        Exclusion Criteria:

          -  Has disseminated or extrapulmonary NTM

          -  Has end-stage NTM-PD or treatment-refractory NTM-PD and is unlikely to respond to
             protocol-specified SOC treatment

          -  Had isolation on sputum cultures of any species of Mycobacterium other than a species
             included in MAC within the past 6 months

          -  Had prior isolation of MAC with macrolide resistance

          -  Has received any systemic (oral or IV) or inhaled antibiotic with activity against MAC
             between consent and randomization

          -  Has a potentially confounding underlying pulmonary disease, including but not limited
             to cystic fibrosis, active pulmonary malignancy (primary or metastatic),
             NTM-hypersensitivity disease pneumoconiosis, or another advanced lung disease with a %
             predicted FEV1<30%

          -  Other exclusion criteria per protocol