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肺结核治疗新方案的随机、适应性、剂量范围、开放标签试验 (RAD-TB)

2026年10月29日 更新者：National Institute of Allergy and Infectious Diseases (NIAID)

肺结核治疗新方案的 2 期随机、适应性、剂量范围、开放标签试验

A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).

A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)].

The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of study treatment (experimental or SOC, based on treatment arm assignment) followed by 18 weeks of SOC continuation phase treatment with 346 participants in Wave 1: 49-50 participants in each experimental treatment arm and 98-100 participants in the SOC treatment arm.

研究概览

地位

暂停

条件

干预/治疗

研究类型

介入性

注册 (估计的)

341

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

  • 乌干达
      • Kampala、乌干达
        • 12401, Joint Clinical Research Centre (JCRC)/Kampala CRS
      • Kampala、乌干达
        • 30293 MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
  • 南非
      • Cape Town、南非、6850
        • 31793, South African Tuberculosis Vaccine Initiative (SATVI) CRS
      • Cape Town、南非、7700
        • 31792, University of Cape Town Lung Institute (UCTLI) CRS
      • Durban、南非、4001
        • 31422, CAPRISA eThekwini CRS
      • Durban、南非、4052
        • 11201, Durban International CRS
      • Johannesburg、南非、1862
        • 12301, Soweto ACTG CRS
      • Johannesburg、南非、2193
        • 11101, Wits Helen Joseph (WITS HJH) CRS
      • Rustenburg、南非
        • 31684, Rustenburg CRS
  • 博茨瓦纳
      • Gaborone、博茨瓦纳、0000
        • 12701, Gaborone CRS
  • 印度
      • Pune、印度、411001
        • 31441, Byramjee Jeejeebhoy Government Medical College (BJGMC) CRS
  • 墨西哥
      • Mexico City、墨西哥、14080
        • 32078, Nutrición-Mexico CRS
  • 巴西
      • Porto Alegre、巴西、91350
        • 12201, Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS
      • Rio de Janeiro、巴西、21040
        • 12101, Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
  • 泰国
      • Bangkok、泰国、10700
        • 5115, Siriraj Hospital, Mahidol University NICHD CRS
      • Chiang Mai、泰国、50200
        • 31784, Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
      • Pathum Wan、泰国、10330
        • 31802, Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
    • Changwat Chiang Rai
      • Chiang Rai、Changwat Chiang Rai、泰国、57000
        • 5116 Chiangrai Prachanukroh Hospital NICHD CRS
  • 津巴布韦
      • Harare、津巴布韦
        • 30313, Milton Park CRS
  • 海地
      • Port-au-Prince、海地、6110
        • 30022, Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
      • Port-au-Prince、海地、6110
        • 31730, GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
  • 秘鲁
      • Lima、秘鲁、15063
        • 11301, Barranco CRS
      • Lima、秘鲁
        • 11302, San Miguel CRS San Miguel
    • Lima Province
      • Lima、Lima Province、秘鲁、15234
        • 31985, Socios En Salud Sucursal Perú CRS
  • 肯尼亚
      • Eldoret、肯尼亚、30100
        • 12601, Moi University Clinical Research Center (MUCRC) CRS
      • Kericho、肯尼亚、20200
        • 12501, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
  • 菲律宾
      • Cavite、菲律宾、4118
        • 31981, TB HIV Innovations and Clinical Research Foundation Corp.
  • 越南
      • Hanoi、越南、100000
        • 32483 National Lung Hospital CRS
  • 马拉维
      • Blantyre、马拉维
        • 30301, Blantyre CRS
      • Lilongwe、马拉维、A-104
        • 12001, Malawi CRS

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 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Pulmonary TB (among individuals either without history of prior TB treatment or with history of TB treatment completed more than 2 years prior to study entry), identified within 7 days prior to study entry by at least one sputum specimen positive for Mtb by Xpert. Semiquantitative Mtb results of "medium" or "high" from Xpert MTB/RIF Ultra are required.

  2. Pulmonary TB with documented INH susceptibility (by Line Probe Assay (LPA) or Xpert MTB/XDR or other validated molecular test) and with documented RIF susceptibility (by LPA or Xpert MTB/RIF or Xpert MTB/RIF Ultra or other validated molecular test) within 7 days prior to study entry.

  3. Documentation of HIV-1 infection status, as below:

    Presence or absence of HIV-1 infection, as documented by:

    • Any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, any time prior to study entry. AND for a positive result confirmation by one of the following:
    • A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used), or
    • HIV-1 antigen, or
    • Plasma HIV-1 RNA viral load, or
    • A licensed Western blot

  4. For individuals with HIV: CD4+ cell count ≥100 cells/mm3 based on testing performed within 30 days prior to study entry.

  5. For individuals with HIV: Currently being treated with dolutegravir-based antiretroviral therapy (ART), or plan to initiate dolutegravir-based ART at or before study week 8.

  6. Individuals age ≥18 years.

  7. The following laboratory values obtained within 7 days prior to study entry at any network-approved non-U.S. laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs:

    • Serum or plasma alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)
    • Serum or plasma total bilirubin ≤2 times ULN
    • Serum or plasma creatinine ≤2 times ULN
    • Serum or plasma potassium ≥3.5 mEq/L
    • Serum or plasma magnesium ≥1.0 mEq/L (≥0.500 mmol/L)
    • Absolute neutrophil count (ANC) ≥1500/mm^3
    • Hemoglobin ≥9.0 g/dL
    • Platelet count ≥100,000/mm^3
    • Negative for, hepatitis B surface antigen (HBsAg)
    • Negative for hepatitis C virus (HCV) antibody (or if HCV antibody positive, must have a negative HCV PCR)

  8. For female study candidates who are of reproductive potential, negative pregnancy test (urine HCG or serum β-HCG) within 3 days (72 hours) prior to entry by any network-approved non-U.S. laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.

    Females who are of reproductive potential and who participate in sexual activity that could lead to pregnancy must agree to use at least two of the following forms of birth control while receiving TB study medications and for 12 months after stopping study medications:

    • Male or female condoms
    • Diaphragm or cervical cap (with spermicide, if available)
    • Intrauterine device (IUD) or intrauterine system (IUS)
    • Hormone-based birth control (e.g., oral contraceptives, Depo-Provera, NuvaRing, implants)

    Female study candidates who are of reproductive potential, but who abstain from sexual activity that could lead to pregnancy require no additional contraception.

    Female study candidates who are not of reproductive potential are eligible without requiring the use of contraceptives. Self-reported history is acceptable documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; these candidates are all considered not of reproductive potential.

  9. For male study candidates who engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives while the individual is on study and for 90 days after experimental treatment discontinuation.

    For male study candidates who have undergone successful vasectomy with documented azoospermia or have documented azoospermia for any other reason, are eligible without requiring the use of contraceptives.

  10. For male study candidates with pregnant partners, willingness to use condoms during vaginal intercourse while on study and for 90 days after experimental treatment discontinuation.

  11. For male study candidates, willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation.

  12. Documentation of Karnofsky performance score ≥60 obtained within 14 days prior to study entry.

  13. Chest x-ray obtained within 14 days prior to study entry.

  14. A verifiable address or residence readily accessible for visiting, and willingness to inform the study team of any change of address during study treatment and follow-up period.

  15. Ability and willingness of individual to provide informed consent.

Exclusion Criteria:

  1. More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.
  2. Current extrapulmonary TB, in the opinion of the investigator.
  3. QTcF interval >450 ms within 7 days prior to study entry.
  4. History of or ongoing heart failure.
  5. Personal or family history of congenital QT prolongation.
  6. History of known, untreated, ongoing hypothyroidism.
  7. History of or ongoing bradyarrhythmia.
  8. History of torsades de pointes.
  9. Current Grade 2 or higher peripheral neuropathy.
  10. Other medical conditions (e.g., diabetes, liver or kidney disease, blood disorders, chronic diarrhea), in the opinion of the site investigator, in which the current clinical condition of the participant is likely to prejudice the response to, or assessment of, treatment.
  11. Pregnant or breastfeeding or planning to become pregnant within the next 12 months.
  12. Weight <35 kg.
  13. Unable to take oral medications.
  14. Taking any of prohibited medications.
  15. Known allergy/sensitivity or any hypersensitivity to components of investigational agents or their formulation.
  16. Active drug or alcohol use or dependence; or mental illness (e.g., major depression) that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  17. Taking an investigational drug or vaccine within 30 or more days prior to study entry.

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
有源比较器：Arm 1: Standard of Care (SOC)
  • Weeks 1-8: INH 300 mg, RIF 600 mg, PZA weight-based, EMB weight-based
  • Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance)
药品：Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

其他名称：
  • 异烟肼
药品：Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

其他名称：
  • RIF
药品：Pyrazinamide

PZA will be administered as 500 mg tablets, based on weight, orally once daily.

其他名称：
  • PZA
药品：Ethambutol

EMB will be administered as 400 mg tablets, based on weight, orally once daily.

其他名称：
  • 欧洲工商局
实验性的：Arm 2: Bedaquiline (BDQ), Pretomanid (Pa), and Linezolid (LZD)
  • Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, LZD 600 mg
  • Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance)
药品：Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

其他名称：
  • 异烟肼
药品：Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

其他名称：
  • RIF
药品：Bedaquiline

BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.

其他名称：
  • BDQ
药品：Pretomanid

Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.

其他名称：
  • 帕
药品：Linezolid

LZD 600 mg will be administered as one 600 mg tablet orally once daily.

其他名称：
  • LZD
实验性的：Arm 3A: BDQ, Pa and TBI-223 (1200 mg)
  • Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, TBI-223 1200 mg
  • Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance)
药品：Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

其他名称：
  • 异烟肼
药品：Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

其他名称：
  • RIF
药品：Bedaquiline

BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.

其他名称：
  • BDQ
药品：Pretomanid

Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.

其他名称：
  • 帕
药品：TBI-223

TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.

药品：TBI-223

TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.
实验性的：Arm 3B: BDQ, Pa and TBI-223 (2400 mg)
  • Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, TBI-223 2400 mg
  • Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance)
药品：Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

其他名称：
  • 异烟肼
药品：Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

其他名称：
  • RIF
药品：Bedaquiline

BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.

其他名称：
  • BDQ
药品：Pretomanid

Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.

其他名称：
  • 帕
药品：TBI-223

TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.

药品：TBI-223

TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.
实验性的：Arm 4A: BDQ, Pa and Sutezolid (SZD) (800 mg)
  • Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, SZD 800 mg
  • Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance)
药品：Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

其他名称：
  • 异烟肼
药品：Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

其他名称：
  • RIF
药品：Bedaquiline

BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.

其他名称：
  • BDQ
药品：Pretomanid

Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.

其他名称：
  • 帕
药品：Sutezolid

SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.

其他名称：
  • 苏德
药品：Sutezolid

SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.

其他名称：
  • 苏德
实验性的：Arm 4B: BDQ, Pa and SZD (1600 mg)
  • Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, SZD 1600 mg
  • Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance)
药品：Isoniazid

INH 300 mg will be administered as one tablet orally once daily.

其他名称：
  • 异烟肼
药品：Rifampicin

RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.

其他名称：
  • RIF
药品：Bedaquiline

BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.

其他名称：
  • BDQ
药品：Pretomanid

Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.

其他名称：
  • 帕
药品：Sutezolid

SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.

其他名称：
  • 苏德
药品：Sutezolid

SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.

其他名称：
  • 苏德

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
Difference in mean log10 (Time to positivity (TTP)) slope from longitudinal mycobacteria growth indicator tube (MGIT) liquid culture measurements over the first 6 weeks of treatment
大体时间：Weeks 0, 1, 2, 3, 4 and 6

for each experimental treatment arm compared to the SOC treatment arm.
Weeks 0, 1, 2, 3, 4 and 6
Difference in the cumulative proportion of participants having at least one new Grade 3 or higher adverse event (AE) by week 8 of treatment
大体时间：8 weeks

for each experimental treatment arm compared to the SOC treatment arm.
8 weeks

次要结果测量

结果测量
大体时间
第 8 周时痰培养稳定转化的参与者的累计比例，通过 MGIT 液体培养连续两次测量的培养阴性状态进行测量。
大体时间：8周
8周
治疗前 8 周纵向 MGIT 液体培养测量的平均 log10 TTP 斜率。
大体时间：第 0、1、2、3、4、6 和 8 周
第 0、1、2、3、4、6 和 8 周
治疗第 26 周时出现新的 3 级或更高 AE 的参与者的累积比例。
大体时间：26周
26周
在治疗第 8 周之前由于任何原因永久停止使用研究提供的抗结核药物的参与者的累计比例。
大体时间：8周
8周
在治疗第 8 周之前，由于任何原因永久停用或暂时停用至少一种抗结核药物 ≥3 天的参与者的累计比例。
大体时间：8周
8周
在治疗第 26 周之前由于任何原因永久停用至少一种抗结核药物的参与者的累计比例。
大体时间：26周
26周
治疗第 6 周培养物稳定转化且到第 8 周没有出现新的 3 级或更高 AE 的综合结果。
大体时间：8周
8周
治疗开始后 52 周内持久治愈的参与者比例。
大体时间：52周
52周

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

National Institute of Allergy and Infectious Diseases (NIAID)

合作者

TB Alliance

调查人员

  • 学习椅：Radojka Savic, PharmD, PhD、University of California
  • 学习椅：Kelly Dooley, MD, PhD、Vanderbilt University Medical Center
  • 学习椅：Gustavo Velásquez, MD, MPH、University of California

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

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)

2025年3月11日

初级完成 (估计的)

2027年3月1日

研究完成 (估计的)

2028年1月3日

研究注册日期

首次提交

2023年12月20日

首先提交符合 QC 标准的

2023年12月20日

首次发布 (实际的)

2024年1月5日

研究记录更新

最后更新发布 (实际的)

2026年11月2日

上次提交的符合 QC 标准的更新

2026年10月29日

最后验证

2026年10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

  • A5409
  • DOH-27-032024-5399 (其他标识符：South African National Clinical Trial Registry (SANCTR))
  • 38917 (注册表标识符：DAIDS-ES Registry Number)

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

Individual participant data that underlie results in the publication, after deidentification.

IPD 共享时间框架

Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.

IPD 共享访问标准

  • With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
  • For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
  • By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

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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