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OPC-167832、Delamanid 和 Bedaquiline 4 个月疗程在药物敏感肺结核患者中的安全性和有效性评估

2026年7月17日 更新者：Otsuka Pharmaceutical Development & Commercialization, Inc.

一项多中心、2b/c 期、开放标签、随机、剂量探索试验，以评估 OPC-167832 联合 Delamanid 和 Bedaquiline 为期 4 个月的方案在药物敏感肺结核患者中的安全性和有效性，并与标准治疗

该试验将评估 OPC-167832 联合 Delamanid 和 Bedaquiline 在 DS-TB 受试者中服用 4 个月与服用利福平、异烟肼、乙胺丁醇、吡嗪酰胺 (RHEZ) 服用 6 个月相比的安全性和有效性

研究概览

地位

完全的

条件

干预/治疗

详细说明

这项研究的符合条件的参与者已诊断出肺DS-TB。

这是一项2b/c阶段的多中心，开放标签，随机，剂量调查研究，包括长达26周的治疗期。

在筛查期限长达14天之后，在研究中将随机分组合格的参与者。

随机化将通过在筛选胸部X射线时通过双侧气蚀进行分层（是或否）。 治疗期结束后，将遵循参与者，直到随机分组后12个月。

研究类型

介入性

注册 (实际的)

122

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 南非
      • Cape Town、南非、7100
        • TASK Applied Science, Brooklyn Chest Hospital Premises
      • Cape Town、南非、7700
        • University of CapeTown Lung Center Institute
      • Johannesburg、南非、2092
        • Themba Lethu Clinic Clinical HIV Research Unit (CHRU)
      • Klerksdorp、南非、2574
        • Perinatal HIV Research Unit Tshepong Hospital Complex
      • Pretoria、南非、0152
        • Setshaba Research Center
    • Gauteng
      • Tembisa、Gauteng、南非、1632
        • Aurum Institute - Tembisa Clinical Research Centre

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 65年 (成人、年长者)

接受健康志愿者

不

描述

纳入标准：

  1. 能够在开始任何与试验相关的程序或治疗之前提供书面的知情同意书，并且研究者认为能够遵守试验的所有要求。
  2. 筛选访问时年龄在 18 至 65 岁（含）之间的男性或女性参与者。
  3. 筛选访视时体重 ≥ 35.0 kg。
  4. 新诊断的利福平和异烟肼易感（在筛查样本中）肺结核。
  5. 能自发生痰。
  6. 育龄女性 (FOCBP) 必须同意使用 2 种不同的经批准的节育方法，或者在参与试验期间以及最后一剂 IMP 或 RHEZ 剂量后的 12 周内保持禁欲。
  7. 男性参与者必须同意使用 2 种不同的经批准的节育方法，或者在他们参与试验的整个过程中以及最后一剂 IMP 或 RHEZ 后的 12 周内保持禁欲。

排除标准：

  1. 在筛选时，参与者已知或怀疑对利福平、异烟肼、乙胺丁醇、吡嗪酰胺、DLM 或 BDQ 具有耐药性，这些耐药性由实验室确认或基于流行病学史。
  2. 有临床意义的代谢证据（例如，包括持续或当前的低钾血症[即筛选时钾<3.5 mEq/dL]）、胃肠道、神经、精神、内分泌或肝脏（例如乙型和丙型肝炎）疾病；恶性肿瘤；或其他异常（正在研究的适应症除外）。
  3. 有或目前有临床相关的心血管疾病史，例如心力衰竭、冠心病、不受控制的高血压、心律失常或强烈提示此类问题的症状（例如晕厥或心悸）、快速性心律失常或心肌梗死后的状态。
  4. 已知的出血性疾病或出血性疾病家族史。
  5. 禁止使用 DLM、BDQ、OPC 167832、利福平、异烟肼、吡嗪酰胺或乙胺丁醇的任何疾病或病症。
  6. 过去 2 年内结核分枝杆菌的任何先前治疗。
  7. 在筛选前 3 个月内接受过对结核分枝杆菌有效的药物（例如喹诺酮类）的任何治疗。
  8. 严重肺外结核的临床证据（例如粟粒性结核、腹部结核、泌尿生殖系统结核、骨关节炎结核、结核性脑膜炎）。
  9. 肺矽肺、肺纤维化或研究者认为严重的其他肺部疾病（结核病除外）的证据。 特别是，任何可能干扰 X 射线图像评估、痰液收集或痰液结果解释或以其他方式影响受试者参与试验的潜在病症。
  10. 任何以肌酐清除率/估计肾小球滤过率 (eGFR) < 60 mL/min/1.73 为特征的肾功能损害 m2，或筛选时以丙氨酸转氨酶或天冬氨酸转氨酶 > 2.0 × 临床实验室参考范围正常上限或胆红素 > 2.0 × 临床实验室参考范围正常上限为特征的肝功能损害。
  11. 筛查葡萄糖（非空腹）≥ 200 mg/dL 或糖化血红蛋白 (HbA1c) ≥ 6.5%。
  12. QTcF 在男性参与者中 > 450 毫秒（在女性参与者中 > 470 毫秒），房室传导阻滞 II 或 III，双束传导阻滞，在筛选时或当前或历史上有临床意义的室性心律失常。 其他 ECG 异常，如果研究者认为具有临床意义。
  13. 在指定期限内接受任何违禁药物（见第 6.5.1 节）或在试验期间可能需要违禁伴随治疗的参与者。
  14. 在第 1 天接受第一剂 IMP 或 RHEZ 之前正在哺乳或妊娠试验结果呈阳性的女性参与者。
  15. 目前有严重的药物和/或酒精滥用史，可能导致对试验要求的依从性差，或者在试验过程中对参与者的健康构成风险。
  16. 当前肝炎史或乙型肝炎表面抗原 (HBsAg) 和/或抗丙型肝炎病毒 (HCV) 携带者。
  17. 筛选时可卡因或其他滥用药物（不包括已知的处方兴奋剂和其他处方药和大麻）呈阳性的参与者被排除在外。 如果根据研究者的书面意见，参与者不符合《精神疾病诊断和统计手册》第五版中度至重度物质使用障碍的标准，则药物筛查中可检测到的酒精、大麻、巴比妥类或阿片类药物水平不是排除性的，并且阳性测试并不表示会影响参与者安全或试验结果解释的临床状况，并且在治疗前由医学监督员同意参与。
  18. 在进入试验前 30 天内服用过研究药物的历史。
  19. 有献血困难史。
  20. 给药前 30 天内捐献血液或血浆。
  21. 研究者认为严重精神障碍的病史会使参与者无法参加本试验。
  22. 任何已知的先前接触过 OPC-167832、DLM 或 BDQ 的信息。
  23. 患有研究者认为不应参加试验的严重医学合并症的参与者。
  24. Karnofsky 评分 < 60 的参与者将被排除在试验之外。
  25. 筛选时参与者的活动性严重急性呼吸系统综合症冠状病毒 (SARS-CoV-2) 感染检测呈阳性。
  26. 合并感染 HIV 的参与者未接受由替诺福韦、恩曲他滨/拉米夫定、多替拉韦（即 > 3 个月）组成的稳定抗逆转录病毒治疗方案，或病毒载量可检测到，或 CD4 计数 < 350 个细胞/mm3排除在审判之外。

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Delamanid + Bedaquiline + OPC-167832 10 mg
参与者将每天（QD），Bedaquiline，400 mg，口服片剂，QD，QD，QD 2周，然后每周200毫克，每周三次（TIW）和OPC-167832，1067832，10 mg，QD，QD，QD，QD，QD，QD，QD，400毫克，每天（QD），400 mg，口服片剂，每天获得300毫克的口服片剂的组合方案。
药品：Delamanid
Delamanid (300 mg QD) for 17 weeks
药品：Bedaquiline
Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) for 17 weeks
药品：OPC-167832 10 mg
OPC-167832 (10 mg QD) for 17 weeks
实验性的：Delamanid + Bedaquiline + OPC-167832 30 mg
参与者将获得Delamanid，300 mg，口服片剂，QD，Bedaquiline，400 mg，口服片剂，QD的组合方案，持续2周，然后200 mg，TIW和OPC-167832，30 mg，30 mg，口服片剂，口服片剂，QD总计17周。
药品：Delamanid
Delamanid (300 mg QD) for 17 weeks
药品：Bedaquiline
Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) for 17 weeks
药品：OPC-167832 30 mg
OPC-167832 (30 mg QD) for 17 weeks
实验性的：Delamanid + Bedaquiline + OPC-167832 90毫克
参与者将获得Delamanid，300 mg，口服片剂，QD，Bedaquiline，400 mg，口服片剂，QD的组合方案，持续2周，然后200 mg，TIW和OPC-167832，167832，90 mg，90 mg，口服片剂，QD，QD总计17周。
药品：Delamanid
Delamanid (300 mg QD) for 17 weeks
药品：Bedaquiline
Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) for 17 weeks
药品：OPC-167832 90 mg
OPC-167832 (90 mg QD) for 17 weeks
有源比较器：利福平，异烟肼，乙酰丁醇和吡嗪酰胺（RHEZ）
参与者将口服QD，然后将Rhez收到8周，然后进行18周的Rifampin和Isoniazid总共26周。
药品：RHEZ
RHEZ (RIFAFOUR single dose combination tablets) for 8 weeks
其他名称：
  • RIFAFOUR
药品：Rifampin
Rifampin tablets for 18 weeks
药品：Isoniazid
Isoniazid tablets for 18 weeks

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, TEAEs Related to Study Drug, TEAEs Leading to Study Discontinuation, TEAEs Leading to Death, and All Grade TEAEs Based on DAIDS Criteria
大体时间：From first dose of study drug up to end of follow up period (up to Week 52)

An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment. Serious AE are AEs that leads to death, is life threatening, requires or prolongs hospitalization, significant disability, congenital anomaly or birth defect, and other medically important serious advent.

AEs were graded on a severity 3-point scale as follows: Mild: Discomfort noticed, but no disruption to daily activity.; Moderate: Discomfort sufficient to reduce or affect normal daily activity.;Severe: Inability to work or perform normal daily activity. As pre-specified in statistical analysis plan (SAP),Division of AIDS (DAIDS v2.1) criteria was used and AEs graded as follows:Grade 1-Mild;Grade 2-Moderate;Grade 3-Severe;Grade 4-Life Threatening;Grade 5-Death.
From first dose of study drug up to end of follow up period (up to Week 52)
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities
大体时间：Baseline up to end of follow up period (up to Week 52)
Laboratory assessments included clinical chemistry (Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Total Bilirubin, Calcium, Creatinine, estimated Glomerular Filtration Rate (eGFR), Glucose, Fasting and Non-Fasting, Cholesterol, Inorganic Phosphorus, Magnesium, Potassium, Sodium, Triglycerides and Uric Acid), hematology (Activated Partial Thromboplastin Time, Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio (INR), Absolute CD4+ Count, Absolute Lymphocytes, Absolute Neutrophil Count, Hemoglobin, Platelet Count, White Blood Cell), and urinalysis (Urine Glucose, Blood and Protein). As pre-specified in statistical analysis plan (SAP), Division of AIDS (DAIDS) criteria was used and abnormalities were graded as follows:Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death. Laboratory values with DAIDS Grade ≥3 were considered as potentially clinically relevant abnormalities and are reported here.
Baseline up to end of follow up period (up to Week 52)
Number of Participants With Potentially Clinically Relevant Abnormalities in the Vital Signs
大体时间：Baseline up to end of follow up period (up to Week 52)
Vital signs measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body weight, and body temperature. Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and sitting positions after the participant had been in each position for at least 3 minutes. The participants were categorized based on the clinically relevant vital sign values as per DAIDS criteria pre-specified in SAP. Each vital sign parameter was graded using the DAIDS criteria as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Potentially Life Threatening; Grade 5 - Death. The categories with at least one participant with clinically significant value of any grade for vital signs are reported here.
Baseline up to end of follow up period (up to Week 52)
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities
大体时间：Baseline up to end of follow up period (up to Week 52)
3 ECGs were performed at baseline (Day -1) spaced 5 to 10 minutes apart, and 3 ECGs at all subsequent visits during the treatment and follow-up periods. The categories with at least one participant with clinically relevant ECG abnormalities are reported here.
Baseline up to end of follow up period (up to Week 52)
Number of Participants With an AE Reported as DAIDS Grade 3 or Higher
大体时间：From first dose of study drug up to end of follow up period (up to approximately Week 52)
An AE was defined as any untoward medical occurrence in a clinical trial participant administered a treatment that does not necessarily have a causal relationship with the treatment. All AEs were graded on a 5-point scale according to DAIDS Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death.
From first dose of study drug up to end of follow up period (up to approximately Week 52)
Number of Participants With TEAEs Leading to Discontinuation of Treatment
大体时间：From first dose of the study drug up to end of follow up period (up to approximately Week 52)
An AE was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment.
From first dose of the study drug up to end of follow up period (up to approximately Week 52)
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT) by End of Treatment (Week 17)
大体时间：Week 17
A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% confidence interval (CI) was calculated using Clopper Pearson (exact) confidence interval model.
Week 17
Percentage of Participants Who Achieved SCC in MGIT by End of Treatment (Week 26)
大体时间：Week 26
A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% CI is calculated using Clopper Pearson (exact) confidence interval model.
Week 26

次要结果测量

结果测量
措施说明
大体时间
Percentage of Participants Who Achieved SCC in MGIT by the End of 8 Weeks of Treatment
大体时间：Week 8
A participant was classified as having achieved SCC if he/she achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the 8 weeks of treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% CI is calculated using Clopper Pearson (exact) confidence interval model.
Week 8
Time to Detection of MGIT Cultures
大体时间：Baseline up to Week 52
Time to detection of MGIT cultures was the time assessed, in days, when a sputum culture result was positive using the MGIT system during the routine 42-day incubation period. A longer time to detection represented a lower burden of mycobacterium tuberculosis (MTB) organisms present in the sputum.
Baseline up to Week 52
Percentage of Participants Achieving Negative Sputum Lipoarabinomannan (LAM) by 8 Weeks of Treatment and by End of Treatment
大体时间：Week 8, and End of Treatment Period - Week 17 (for OPC-167832 arms) and Week 26 (for RHEZ arm)
Sputum LAM concentrations were measured on up to 3 samples collected at baseline and postbaseline at Week 8 and at end of treatment. A participant was classified as having achieved negative sputum conversion in LAM if the participant has the first of 2 visits of at least 1 week apart with sputum LAM negative (below the lower limit of quantification) and without a positive sputum LAM result in between. Numeric sputum LAM concentration data was converted to a binary variable using the rule: if the sputum LAM concentration was less than 10 picograms per milliliter (pg/mL) then it was interpreted as a negative result. If the sputum LAM concentration was greater than or equal to 10 pg/mL then it was interpreted as positive result. SCC for LAM was considered to have been achieved if there were negative results at two consecutive visits with non-missing results. 95% CI was calculated using Clopper Pearson (exact) confidence interval model.
Week 8, and End of Treatment Period - Week 17 (for OPC-167832 arms) and Week 26 (for RHEZ arm)
Percentage of Participants With Acquired Drug Resistance
大体时间：Baseline up to Week 52
Acquired resistance was defined as a post-baseline resistant result at any timepoint after a baseline susceptible result. Baseline was defined as Day -1, if Day -1 was missing then Day 1 was used, if day 1 was missing then Week 1 was used. Resistance data was collected for streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, bedaquiline and delamanid. Susceptibility testing (DST) for anti-TB medications was performed on positive M tuberculosis isolates from Day -1 or Day 1 cultures, and on the end of treatment sputum specimen. Percentage of participants who were susceptible at baseline and developed resistance to the indicated drug (class) at any post-baseline visits was summarized.
Baseline up to Week 52
Time to Sputum Culture Conversion (SCC)
大体时间：From the first dose of the study up to the end of the follow-up period (up to Week 52)
Sputum culture conversion occurs when a participant has the first of 2 consecutive visits of at least 7 days apart with sputum cultures negative and without a positive sputum culture result in between, as well as no positive sputum culture after the negative results. If a participant had a positive MGIT culture result throughout the study period, then the participant was considered as not having achieved SCC within the period under consideration. The time to SCC in this case was censored. Time to SCC was calculated from date of first dose using MGIT cultures without the mitigation method measures.
From the first dose of the study up to the end of the follow-up period (up to Week 52)

其他结果措施

结果测量
措施说明
大体时间
Assess the Positron Emission Tomography/Computerized Axial Tomography (PET/CT) Imaging Response Over the Course of Treatment
大体时间：Baseline to Week 26
Positron emission tomography/computerized axial tomography (PET/CT) imaging changes over the course of treatment, using quantitative scan assessment.
Baseline to Week 26
Evaluate the Ribosomal Ribonucleic Acid Synthesis Ratio (RS Ratio) Decline in Sputum
大体时间：Baseline to 12 months post randomization
The decline of ribosomal ribonucleic acid synthesis ratio (RS ratio - a ratio of spacers between the mRNA) in sputum over the course of trial.
Baseline to 12 months post randomization
Assess Whole Blood Transcriptomic Signatures Previously Associated With TB Cure From Serum
大体时间：Screening to 12 months post randomization
The change in whole blood transcriptomic signatures over the course of treatment will be evaluated using ROC curves for association with microbiological and clinical response.
Screening to 12 months post randomization
The Proportion of Participants With Favorable Outcome at 12 Months Post Randomization
大体时间：Baseline to 12 months post randomization
The proportion of subjects with favorable outcome as compared to the 6 months post end of treatment and at 12 months post randomization.
Baseline to 12 months post randomization
Number of Participants With Relapse at 12 Months Post Randomization
大体时间：Baseline to 12 months post randomization
Proportion of participants with relapse at 12 months post randomization.
Baseline to 12 months post randomization

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Otsuka Pharmaceutical Development & Commercialization, Inc.

合作者

Bill and Melinda Gates Foundation

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年4月12日

初级完成 (实际的)

2024年4月8日

研究完成 (实际的)

2024年5月19日

研究注册日期

首次提交

2021年8月20日

首先提交符合 QC 标准的

2022年1月21日

首次发布 (实际的)

2022年2月3日

研究记录更新

最后更新发布 (实际的)

2026年8月12日

上次提交的符合 QC 标准的更新

2026年7月17日

最后验证

2026年7月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 323-201-00006

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

作为本研究结果基础的匿名个人参与者数据 (IPD) 将与研究人员共享，以实现在方法论上合理的研究计划中预先指定的目标。 参与者少于 25 人的小型研究被排除在数据共享之外。

IPD 共享时间框架

数据将在全球市场获得上市许可后提供，或在文章发表后 1-3 年内提供。 数据的可用性没有结束日期。

IPD 共享访问标准

Otsuka 将在 Vivli 数据共享平台上共享数据，该平台可在此处找到：https://vivli.org/ourmember/Otsuka/

IPD 共享支持信息类型

  • 研究方案
  • 树液
  • 企业社会责任

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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