A Phase 2b, Randomised, Multi-center, Partially Blinded Trial Assessing the Safety and Efficacy of Regimens Containing Sorfequiline, Pretomanid and Linezolid in Adults With Newly Diagnosed, Drug-sensitive, Smear Positive Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 22
- 主要终点
- Incidence and characterization of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
The goal of this interventional trial is to evaluate the safety and efficacy of the loading dose regimen 200/100SPaL-4/13 weeks, and the 100SPaL -17 weeks regimen in adults with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis.
Participants (18-65 years) will be randomised 1:1, stratified by country and disease severity, to receive either :
- a sorfequiline loading-dose regimen (200 mg daily for 4 weeks followed by 100 mg daily for 13 weeks) plus pretomanid 200 mg and linezolid 600 mg daily, or
- sorfequiline 100 mg daily for 17 weeks plus pretomanid 200 mg and linezolid 600 mg daily. Study treatment is administered orally once daily with food.
The primary objective is to assess safety through 17 weeks of treatment, including treatment-emergent adverse events, ECG findings, vital signs, laboratory assessments, visual acuity, and peripheral neuropathy. Secondary objectives include assessments of efficacy (time to stable sputum culture conversion; favorable outcome and treatment failure/relapse at 26 and 52 weeks after end of treatment) and pharmacokinetics of trial drugs, with exploratory analyses including predictors of culture conversion, exposure-response relationships, and quality of life.
详细描述
This is a phase 2, randomised, multi-center, partially blinded, clinical trial conducted in 2 treatment arms.
The trial will be performed at multiple centers in South Africa and Tanzania in at approximately 100 participants with DS-TB who meet all the inclusion criteria and none of the exclusion criteria, aged 18 to 65, inclusive. Participants will be randomised to one of the 2 sorfequiline, pretomanid and linezolid containing regimens and will be randomised in 1:1 ratio based on country and severity of disease (AFB 3+ and/or bilateral cavitation). T
The trial will consist of the following periods:
- Screening period: Screening visit, up to 11 days prior to randomisation (Day 1)
- Treatment Period: approximately 100 participants will be randomised equally to the 2 treatment arms below:
- Sorfequiline 200 mg + pretomanid 200 mg + linezolid 600 mg for 4 weeks followed by sorfequiline 100 mg for 13 weeks
- Sorfequiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 17 week
- Follow-up Period: 52 weeks after end of treatment
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DS-TB as defined as sensitive to rifampicin and isoniazid by rapid sputum-based test AND either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB
- •Of non-childbearing potential OR using effective birth control methods
- •Body weight ≥ 35 k
排除标准
- •Karnofsky score < 60 at screening
- •Any evidence of extrapulmonary TB
- •Cardiovascular or QT prolongation risk factors Pregnant or breast-feeding
- •Laboratory abnormalities as defined in the protocol. • For participants living with HIV only:
- •CD4+ count<200 cells/μL.
- •WHO Clinical Stage 4 HIV disease
- •Participant does not agree to use DTG/TFV/3TC during study treatment if ARV therapy is indicated
- •If initiation of ARV therapy is indicated, participants who are known to be intolerant, non-responsive to DTG/TFV/3TC or have DTG/TFV/3TC as a contraindication.
研究组 & 干预措施
Sorfequline 200/100-Pretomanid 200mg-Linezolid 600mg (Loading Dose)
Regimen (17 weeks total):
Weeks 1-4: Sorfequiline 200 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Weeks 5-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily
干预措施: Linezolid (Drug)
Sorfequiline 100-Pretomanid 200mg-Linezolid 600mg (No Loading Dose)
Regimen (17 weeks total):
Weeks 1-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Includes sorfequiline placebo tablets during first 4weeks to maintain blinding vs the loading regimen.
干预措施: Pretomanid (Drug)
Sorfequiline 100-Pretomanid 200mg-Linezolid 600mg (No Loading Dose)
Regimen (17 weeks total):
Weeks 1-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Includes sorfequiline placebo tablets during first 4weeks to maintain blinding vs the loading regimen.
干预措施: Linezolid (Drug)
Sorfequiline 100-Pretomanid 200mg-Linezolid 600mg (No Loading Dose)
Regimen (17 weeks total):
Weeks 1-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Includes sorfequiline placebo tablets during first 4weeks to maintain blinding vs the loading regimen.
干预措施: sorfequiline (Drug)
Sorfequline 200/100-Pretomanid 200mg-Linezolid 600mg (Loading Dose)
Regimen (17 weeks total):
Weeks 1-4: Sorfequiline 200 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Weeks 5-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily
干预措施: sorfequiline (Drug)
Sorfequline 200/100-Pretomanid 200mg-Linezolid 600mg (Loading Dose)
Regimen (17 weeks total):
Weeks 1-4: Sorfequiline 200 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Weeks 5-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily
干预措施: Pretomanid (Drug)
结局指标
主要结局
Incidence and characterization of treatment-emergent adverse events (TEAEs)
时间窗: Through 17 weeks of treatment
Includes severity, relationship to study drugs, seriousness, TEAEs leading to discontinuation, and TEAEs leading to death; plus safety monitoring endpoints (ECG, vital signs, clinical labs, visual acuity changes, peripheral neuropathy changes.
次要结局
- Time to stable sputum culture conversion (SSCC) to negative(Through 17 weeks of treatment)
- Proportion with favorable outcome(26 weeks after EOT; 52 weeks after EOT)