A5300B/I2003B/PHOENIx A Phase III, open-label, multicenter trial with a cluster-randomized superiority design to compare the efficacy and safety of delamanid (DLM) versus isoniazid (INH) for preventing confirmed or probable active TB during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5,610
- 试验地点
- 2
- 主要终点
- % of participants with confirmed or probable active TB at any time between Day 0 and the week 96 study visit TB diagnoses will be reviewed by the independent outcomes review committee to assess whether the HHC had TB, if it was confirmed or probable TB,and if it was MDR-TB..% of participants who permanently discontinue randomized study drug due to a treatment-related AE.Requiring discontinuation as defined in the protocol, or in the opinion of the site investigator is a treatment-limiting AE
研究概览
简要总结
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 experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 1.00 Day(s) 至 85.01 Year(s)（—）
- 性别
- All
入选标准
- •INDEX CASE:age greater >18 years, patients with Pulmonary MDR-TB, Ability and willingness of the index case to provide informed consent to access the HH and approach HH members for evaluation. HH of index case has at least one reported HHC.HOUSEHOLD CONTACTS : Currently lives or lived in the same dwelling unit or plot of land and shares or has shared the same housekeeping arrangements as the index case and who reports exposure within 90 days prior to the index case starting MDR-TB treatment. Also, shared greater than 4 hours of indoor airspace with the index case during any one-week period prior to the index case starting MDR-TB treatment.;HHCs must be in one of the following high-risk groups:All children
- •5 years old at the time of enrollment ,Adults, adolescents, and children > 5 years of age who are TST+, Adults, adolescents, and children greater > 5 years of age who are HIV-infected or are non-HIV immunosuppressed regardless of TST or IGRA status. HIV-1 infection status must be documented , The following specific laboratory values for infants, children, adolescents, and adults obtained within 30 days prior to study entry by any DAIDS-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
排除标准
- •INDEX CASE :enrolled previously :HHC: TB: Receipt of more than 30 cumulative days of INH,rifamycin,fluoroquinolone,or DLM,Evidence of acute hepatitis ,abdominal pain,nausea & vomiting, jaundice, dark urine,& or light stools in the 90 days prior to study entry, liver cirrhosis .Peripheral neuropathy ,allergy sensitivity or any hypersensitivity to components of study drugs or their formulation,Serious illness.
- •Medication with potential for adverse drug-drug interactions, QT prolongation.
- •Taken an investigational IP or vaccine within 30 days prior to study entry .cardiovascular disorder, active drug or alcohol use or dependence.
结局指标
主要结局
% of participants with confirmed or probable active TB at any time between Day 0 and the week 96 study visit TB diagnoses will be reviewed by the independent outcomes review committee to assess whether the HHC had TB, if it was confirmed or probable TB,and if it was MDR-TB..% of participants who permanently discontinue randomized study drug due to a treatment-related AE.Requiring discontinuation as defined in the protocol, or in the opinion of the site investigator is a treatment-limiting AE
时间窗: Measured through Week 96
次要结局
- Percent of participants with confirmed active MDR-TB at any time between Day 0 and the week 96 study visit(Measured through Week 96)
- Percent of participants who died from any cause at any time between Day 0 and 96 weeks of follow-up .(Deaths will be reviewed by the independent outcomes review committee to assess whether the HHC had TB at the time of death, possibly undiagnosed, and relatedness of the death to TB.)
- Percent of participants who died from any cause at any time between Day 0 and 96 weeks of follow-up, or with confirmed or probable active TB at any time between Day 0 and the week 96 study visit.(Deaths and TB diagnoses will be reviewed by the independent outcomes review committee to assess whether the HHC had TB at the time of death, possibly undiagnosed, and relatedness of the death to TB; and whether the HHC had TB, if it was confirmed or probable TB, and if it was MDR-TB.)
- Percent of participants with a Grade 3 or higher adverse event during the period receiving randomized study drug (DLM or INH)(If a HHC has a Grade 3 or higher adverse event prior to starting randomized study drug, then the same event will only be considered during follow-up if the grade worsens.)