Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD)
Conditions
Keywords
Mycobacterium avium Complex, MAC, Pulmonary disease
Brief summary
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.
Interventions
DRUGPlacebo
Placebo-matching capsules was administered orally.
DRUGSPR720 500 mg
SPR720 500 mg (250 mg × 2 capsules) was administered orally.
DRUGSPR720 1000 mg
SPR720 500 mg (250 mg × 4 capsules) was administered orally.
Sponsors
Spero Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | Days 1 through 56 (end of the treatment [EOT]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Susceptibility in SPR719 From Days 1 through 56 (EOT) in the micro-ITT Population | Days 1 through 56 (EOT) | Susceptibility is ≥4-fold increase in minimum inhibitory concentration for same pathogen identified at Baseline. |
| Slope of the Weekly Sputum Log10 CFU/mL Change From Days 1 Through 28 in micro-ITT Population | 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 | Days 1 through 56 (EOT) | — |
| Change from Baseline in the Sputum Log10 CFU/mL in the micro-ITT Population | Days 1 through 56 (EOT) | — |
| Change from Baseline in the Sputum TTP Using MGIT in micro-ITT Population | Days 1 through 56 (EOT) | — |
| Time to Negative Sputum Culture in micro-ITT Population | Days 1 through 56 (EOT) | — |
| Clinical Response in the micro-ITT Population | Baseline up to Day 84 (FU) | Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened. |
| Clinical Response in the Clinically Evaluable (CE) Populations | Baseline up to Day 84 (FU) | 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 | Baseline up to FU Day 84 | 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. |
| Percent with Negative Sputum Culture in micro-ITT Population | Days 14 through Day 84 (FU) | — |
| Change From Baseline in 7-point Patient Global Impression of Change (PGI-C) scale for Quality of Life (QOL) Assessments | Baseline up to FU Day 84 | The PGI-C scale is a patient-reported rating of improvement on a 7-point verbal descriptor scale. |
| Change From Baseline in Flu, COVID-19, or Other Illness Questionnaire (2 questions) for Quality of Life (QOL) Assessments | Baseline up to FU Day 84 | 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 Patient-Reported Outcomes Measurement Information System (PROMIS®) V1.0 Fatigue Short form 7a scale for Quality of Life (QOL) Assessments | Baseline up to FU Day 84 | 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. |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | From first dose of study drug (Day 1) up to follow up Day 84 | 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. |
| Maximum Plasma Concentration (Cmax) (Intensive PK group only) | Pre-dose and post-dose on Days 1 and 14 | — |
| Time to reach Cmax (Tmax) (Intensive PK group only) | Pre-dose and post-dose on Days 1 and 14 | — |
| Area Under the Concentration-time Curve (AUC0-τ) (Intensive PK group only) | Pre-dose and post-dose on Days 1 and 14 | — |
| Accumulation Ratio of SPR719 Cmax on Day 14 Compared to Day 1 (Intensive PK group only) | Pre-dose and post-dose on Days 1 and 14 | — |
| Accumulation Ratio of SPR719 AUC0-τ on Day 14 Compared to Day 1 (Intensive PK group only) | Pre-dose and post-dose on Days 1 and 14 | — |
| Change From Baseline in 6-point Patient Global Impression of Severity (PGI-S) Scale for Quality of Life (QOL) Assessments | Baseline up to FU Day 84 | 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. |
Countries
United States
Outcome results
None listed