Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease

Phase 2

Terminated

Conditions: Mycobacterium Avium Complex
Non-tuberculous Mycobacterium Pulmonary Disease

Interventions: Drug: SPR720
Drug: Placebo
Drug: Open-label Standard of Care

Registration Number: NCT04553406

Lead Sponsor: Spero Therapeutics

Brief 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SPR720 low dose	SPR720	SPR720 500 mg administered orally once daily for 28 days.
Placebo	Placebo	Placebo administered orally once daily for 28 days
Standard of Care (SOC)	Open-label Standard of Care	Standard of Care regimen per the Investigator's discretion.
SPR720 high dose	SPR720	SPR720 1000 mg administered orally once daily for 28 days.

Primary Outcome Measures

Name	Time	Method
Time to Reach Maximum Plasma Concentration (Tmax) of SPR719	Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719	Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) of SPR719	Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose	SPR719 is the active moiety of the prodrug SPR720. Blood samples were planned to be taken at a subset of study sites in order to conduct intensive pharmacokinetic (PK) evaluation.
Accumulation Ratio of SPR719	Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Meaningful Change in Physical Examination Findings	Days 1, 7, 14, 21, 28, and 56	Full physical examination were conducted on Day 1 and 28 days after last dose (Day 56) and included, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system. Symptom-directed physical examinations were conducted at study visits on Days 7, 14, 21, and 28.
Changes From Baseline in Laboratory Tests	Days 1, 7, 14, 21, 28, and 56
Changes From Baseline in Vital Sign Measurements	Days 1, 7, 14, 21, 28, and 56	Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From first dose of study drug (Day 1) up to 28 days after last dose (56 days)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation patient 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. This includes any newly occurring event or previous condition that has increased in severity or frequency since starting active or randomized treatment. The Investigator assessed the intensity for each AE reported during the study using the latest version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, as Mild, Moderate, Severe, Life-threatening, or Death.
Number of Participants Who Received Any Concomitant Medication During the Study	Day 1 to Day 56
Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories	Days 1, 7, 14, 21, 28, and 56
Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings	Days 1, 14, 28, and 56	Standard 12-lead electrocardiogram (ECG) assessments included heart rate, cardiac rhythm, PR interval, RR interval, QRS interval, QT interval and QTC interval. Clinical significance was determined by the investigator.
Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests	Days 1, 7, 14, 21, 28, and 56	Clinical laboratory tests included serum chemistry, hematology, coagulation tests, and urinalysis. The investigator determined whether any changes in laboratory values were clinically significant based on the condition of the participant and the extent and duration of the deviation from the reference range.