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

Spero Therapeutics25 enrolled

Overview

The purpose of the study is to evaluate 1. The microbiological response and clinical efficacy of SPR720 compared with placebo in participants with nontuberculous mycobacteria pulmonary disease (NTM-PD). 2. The safety and tolerability of SPR720 in participants with NTM- PD 3. The pharmacokinetic (PK) of SPR719, active moiety, following orally (po) administered prodrug SPR720 in participants with NTM-PD.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD)

Interventions

Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Has a prior diagnosis of NTM-PD due to MAC according to American Thoracic Society (ATS) criteria 2. Has at least one prior lower respiratory culture (sputum or bronchoalveolar lavage \[BAL\]) positive for MAC in the 12 months prior to consent 3. Has an induced sputum culture at Screening positive for MAC by quantitative culture on solid agar 4. 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: 1. Has a history of successful treatment with sputum culture conversion to negative 2. Has recent sputum or BAL culture evidence of recurrent or relapsed disease and 3. Has been off therapy for at least 3 months prior to consent 5. Has clinical signs and symptoms within the 6 weeks prior to consent that are consistent with NTM-PD with ≥2 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 (temperature \>38ºC or \>100.4ºF) 8. night sweats 9. loss of appetite 10. unintended weight loss 11. wheezing 12. chest pain 6. 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: 1. In the opinion of the Investigator, is not a candidate for a 5-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) 2. Has disseminated or extrapulmonary NTM disease 3. Has end-stage NTM-PD or treatment-refractory NTM-PD 4. 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 5. 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 6. 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.

Locations (28)

Medical Facility

Birmingham, Alabama, United States

Medical Facility

Fresno, California, United States

Medical Facility

Los Angeles, California, United States

Medical Facility

Newport Beach, California, United States

Medical Facility

Northridge, California, United States

Medical Facility

Santa Clarita, California, United States

Medical Facility

Washington D.C., District of Columbia, United States

Medical Facility

Kissimmee, Florida, United States

Medical Facility

Loxahatchee Groves, Florida, United States

Medical Facility

Miami, Florida, United States

...and 18 more locations

Outcomes

Primary Outcomes

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

Time frame: Days 1 through 56 (end of the treatment [EOT])

Secondary Outcomes

Slope of the Weekly Sputum Log10 CFU/mL Change From Days 1 Through 28 in micro-ITT Population

Time frame: Days 1 through 28

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

Time frame: Days 1 through 56 (EOT)

Change from Baseline in the Sputum Log10 CFU/mL in the micro-ITT Population

Time frame: Days 1 through 56 (EOT)

Change from Baseline in the Sputum TTP Using MGIT in micro-ITT Population

Time frame: Days 1 through 56 (EOT)

Time to Negative Sputum Culture in micro-ITT Population

Time frame: Days 1 through 56 (EOT)

Percent with Negative Sputum Culture in micro-ITT Population

Time frame: Days 14 through Day 84 (FU)

Changes in Susceptibility in SPR719 From Days 1 through 56 (EOT) in the micro-ITT Population

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

Time frame: Days 1 through 56 (EOT)

Clinical Response in the micro-ITT Population

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

Time frame: Baseline up to Day 84 (FU)

Clinical Response in the Clinically Evaluable (CE) Populations

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

Time frame: Baseline up to Day 84 (FU)

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.

Time frame: Baseline up to FU Day 84

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.

Time frame: Baseline up to FU Day 84

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

The PGI-C scale is a patient-reported rating of improvement on a 7-point verbal descriptor scale.

Time frame: Baseline up to FU Day 84

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.

Time frame: Baseline up to FU Day 84

Change from Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS®) V1.0 Fatigue Short form 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.

Time frame: Baseline up to FU Day 84

Number of Participants with Treatment Emergent Adverse Events (TEAEs)

An adverse event (AE) 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.

Time frame: From first dose of study drug (Day 1) up to follow up Day 84

Maximum Plasma Concentration (Cmax) (Intensive PK group only)