NCT05496374已完成2 期
A Randomized, Investigator-Blinded, Placebo-Controlled, Multicenter, Phase 2, Dose-Ranging Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
The purpose of the study is to evaluate
- The microbiological response and clinical efficacy of SPR720 compared with placebo in participants with nontuberculous mycobacteria pulmonary disease (NTM-PD).
- The safety and tolerability of SPR720 in participants with NTM- PD
- The pharmacokinetic (PK) of SPR719, active moiety, following orally (po) administered prodrug SPR720 in participants with 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)
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 prior diagnosis of NTM-PD due to MAC according to American Thoracic Society (ATS) criteria
- •Has at least one prior lower respiratory culture (sputum or bronchoalveolar lavage [BAL]) positive for MAC in the 12 months prior to consent
- •Has an induced sputum culture at Screening positive for MAC by quantitative culture on solid agar
- •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:
- •Has a history of successful treatment with sputum culture conversion to negative
- •Has recent sputum or BAL culture evidence of recurrent or relapsed disease and
- •Has been off therapy for at least 3 months prior to consent
- •Has clinical signs and symptoms within the 6 weeks prior to consent that are consistent with NTM-PD with ≥2 of the following:
- •chronic cough
- •frequent throat clearing
- •shortness of breath (dyspnea)
- •coughing up of blood (hemoptysis)
- •excessive mucus (sputum) production
- •fever (temperature >38ºC or >100.4ºF)
- •night sweats
- •loss of appetite
- •unintended weight loss
- •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
排除标准
- •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)
- •Has disseminated or extrapulmonary NTM disease
- •Has end-stage NTM-PD or treatment-refractory NTM-PD
- •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
- •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
- •Prior exposure to SPR
- •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.
研究组 & 干预措施
Investigator Blind: Placebo
Placebo Comparator
Participants received SPR720 matching-placebo capsules, orally, once daily (QD) for 56 days.
干预措施: Placebo (Drug)
Investigator Blind: SPR720 500 mg
Experimental
Participants received SPR720 500 mg (250 mg × 2) capsules along with 2 SPR720 matching- placebo capsules, orally, QD for 56 days.
干预措施: SPR720 500 mg (Drug)
Investigator Blind: SPR720 1000 mg
Experimental
Participants received SPR720 1000 mg (250 mg × 4) capsules, orally, QD for 56 days.
干预措施: SPR720 1000 mg (Drug)
Open-label: SPR720 1000 mg
Experimental
Participants received SPR720 1000 mg (250 mg × 4) capsules, orally, QD for 56 days.
干预措施: SPR720 1000 mg (Drug)
Open-label: SPR720 500 mg
Experimental
Participants received SPR720 500 mg (250 mg × 2) capsules, orally, twice daily (BID) for 56 days.
干预措施: SPR720 500 mg (Drug)
结局指标
主要结局
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
时间窗: Days 1 through 56 (end of the treatment [EOT])
次要结局
- 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))
- Percent with Negative Sputum Culture in micro-ITT Population(Days 14 through Day 84 (FU))
- Changes in Susceptibility in SPR719 From Days 1 through 56 (EOT) in the micro-ITT Population(Days 1 through 56 (EOT))
- Clinical Response in the micro-ITT Population(Baseline up to Day 84 (FU))
- Clinical Response in the Clinically Evaluable (CE) Populations(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(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(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(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(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(Baseline up to FU Day 84)
- Number of Participants with Treatment Emergent Adverse Events (TEAEs)(From first dose of study drug (Day 1) up to follow up Day 84)
- 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)
研究者
研究点 (2)
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相关资讯
Spero Therapeutics Halts SPR720 Development After Phase II Failure, Focuses on Tebipenem HBr and SPR206• Spero Therapeutics discontinued the development of SPR720 after it failed to meet the primary endpoint in a Phase IIa trial for non-tuberculous mycobacterial pulmonary disease (NTM-PD).
• The interim analysis of SPR720 showed no significant antimicrobial effect compared to placebo, leading to the suspension of the program and a 39% staff reduction.
• Spero will now prioritize tebipenem HBr, licensed to GSK, and SPR206, with ongoing trials and FDA clearance for Phase II contingent on funding.
• The company's stock price declined following the announcement, reflecting investor concerns about the future of its antibiotic pipeline.last yearSpero Therapeutics Halts SPR720 Development After Phase IIa Failure• Spero Therapeutics discontinued the development of SPR720 after it failed to meet the primary endpoint in a Phase IIa trial for non-tuberculous mycobacterial pulmonary disease (NTM-PD).
• The interim analysis of the trial showed no significant antimicrobial effect compared to placebo, leading to the suspension of the SPR720 program.
• Spero plans to focus on its other antibiotic programs, including tebipenem HBr and SPR206, while also reducing its workforce by 39% to extend its cash runway.
• The company's stock price declined by over 17% following the announcement, reflecting investor concerns about the future of the SPR720 program.last year