A Randomized, Partially Blinded, Placebo- and Comparator-Controlled, Multicenter, Phase 2a, Dose Ranging, Proof-of-Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SPR720 as Compared With Placebo or Standard of Care for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Time to Reach Maximum Plasma Concentration (Tmax) of SPR719
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •chronic cough
- •frequent throat clearing
- •shortness of breath (dyspnea)
- •coughing up of blood (hemoptysis)
- •excessive mucus (sputum) production
- •night sweats
- •loss of appetite
- •unintended weight loss
- •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
排除标准
- •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
研究组 & 干预措施
SPR720 low dose
SPR720 500 mg administered orally once daily for 28 days.
干预措施: SPR720 (Drug)
SPR720 high dose
SPR720 1000 mg administered orally once daily for 28 days.
干预措施: SPR720 (Drug)
Placebo
Placebo administered orally once daily for 28 days
干预措施: Placebo (Drug)
Standard of Care (SOC)
Standard of Care regimen per the Investigator's discretion.
干预措施: Open-label Standard of Care (Drug)
结局指标
主要结局
Time to Reach Maximum Plasma Concentration (Tmax) of SPR719
时间窗: 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
时间窗: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) of SPR719
时间窗: 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
时间窗: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
次要结局
- Number of Participants With Clinically Meaningful Change in Physical Examination Findings(Days 1, 7, 14, 21, 28, and 56)
- 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)
- 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))
- 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)
- Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests(Days 1, 7, 14, 21, 28, and 56)