폐결핵 치료를 위한 새로운 치료법에 대한 무작위, 적응형, 용량 범위 지정, 공개 라벨 시험 (RAD-TB)
폐결핵 치료를 위한 새로운 치료법에 대한 무작위, 적응형, 용량 범위, 공개 라벨 시험 2상
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.
연구 개요
상태
정황
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 장소
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Cape Town, 남아프리카, 6850
- 31793, South African Tuberculosis Vaccine Initiative (SATVI) CRS
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Cape Town, 남아프리카, 7700
- 31792, University of Cape Town Lung Institute (UCTLI) CRS
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Durban, 남아프리카, 4001
- 31422, CAPRISA eThekwini CRS
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Durban, 남아프리카, 4052
- 11201, Durban International CRS
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Johannesburg, 남아프리카, 1862
- 12301, Soweto ACTG CRS
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Johannesburg, 남아프리카, 2193
- 11101, Wits Helen Joseph (WITS HJH) CRS
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Rustenburg, 남아프리카
- 31684, Rustenburg CRS
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Blantyre, 말라위
- 30301, Blantyre CRS
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Lilongwe, 말라위, A-104
- 12001, Malawi CRS
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Mexico City, 멕시코, 14080
- 32078, Nutrición-Mexico CRS
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Hanoi, 베트남, 100000
- 32483 National Lung Hospital CRS
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Gaborone, 보츠와나, 0000
- 12701, Gaborone CRS
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Porto Alegre, 브라질, 91350
- 12201, Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS
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Rio de Janeiro, 브라질, 21040
- 12101, Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
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Port-au-Prince, 아이티, 6110
- 30022, Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
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Port-au-Prince, 아이티, 6110
- 31730, GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
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Kampala, 우간다
- 12401, Joint Clinical Research Centre (JCRC)/Kampala CRS
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Kampala, 우간다
- 30293 MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
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Pune, 인도, 411001
- 31441, Byramjee Jeejeebhoy Government Medical College (BJGMC) CRS
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Harare, 짐바브웨
- 30313, Milton Park CRS
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Eldoret, 케냐, 30100
- 12601, Moi University Clinical Research Center (MUCRC) CRS
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Kericho, 케냐, 20200
- 12501, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
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Bangkok, 태국, 10700
- 5115, Siriraj Hospital, Mahidol University NICHD CRS
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Chiang Mai, 태국, 50200
- 31784, Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
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Pathum Wan, 태국, 10330
- 31802, Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
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Changwat Chiang Rai
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Chiang Rai, Changwat Chiang Rai, 태국, 57000
- 5116 Chiangrai Prachanukroh Hospital NICHD CRS
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Lima, 페루, 15063
- 11301, Barranco CRS
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Lima, 페루
- 11302, San Miguel CRS San Miguel
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Lima Province
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Lima, Lima Province, 페루, 15234
- 31985, Socios En Salud Sucursal Perú CRS
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Cavite, 필리핀 제도, 4118
- 31981, TB HIV Innovations and Clinical Research Foundation Corp.
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
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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.
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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.
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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
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For individuals with HIV: CD4+ cell count ≥100 cells/mm3 based on testing performed within 30 days prior to study entry.
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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.
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Individuals age ≥18 years.
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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)
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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.
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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.
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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.
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For male study candidates, willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation.
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Documentation of Karnofsky performance score ≥60 obtained within 14 days prior to study entry.
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Chest x-ray obtained within 14 days prior to study entry.
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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.
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Ability and willingness of individual to provide informed consent.
Exclusion Criteria:
- More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.
- Current extrapulmonary TB, in the opinion of the investigator.
- QTcF interval >450 ms within 7 days prior to study entry.
- History of or ongoing heart failure.
- Personal or family history of congenital QT prolongation.
- History of known, untreated, ongoing hypothyroidism.
- History of or ongoing bradyarrhythmia.
- History of torsades de pointes.
- Current Grade 2 or higher peripheral neuropathy.
- 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.
- Pregnant or breastfeeding or planning to become pregnant within the next 12 months.
- Weight <35 kg.
- Unable to take oral medications.
- Taking any of prohibited medications.
- Known allergy/sensitivity or any hypersensitivity to components of investigational agents or their formulation.
- 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.
- Taking an investigational drug or vaccine within 30 or more days prior to study entry.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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활성 비교기: Arm 1: Standard of Care (SOC)
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INH 300 mg will be administered as one tablet orally once daily.
다른 이름들:
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.
다른 이름들:
PZA will be administered as 500 mg tablets, based on weight, orally once daily.
다른 이름들:
EMB will be administered as 400 mg tablets, based on weight, orally once daily.
다른 이름들:
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실험적: Arm 2: Bedaquiline (BDQ), Pretomanid (Pa), and Linezolid (LZD)
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INH 300 mg will be administered as one tablet orally once daily.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
다른 이름들:
LZD 600 mg will be administered as one 600 mg tablet orally once daily.
다른 이름들:
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실험적: Arm 3A: BDQ, Pa and TBI-223 (1200 mg)
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INH 300 mg will be administered as one tablet orally once daily.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
다른 이름들:
TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal. TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal. |
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실험적: Arm 3B: BDQ, Pa and TBI-223 (2400 mg)
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INH 300 mg will be administered as one tablet orally once daily.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
다른 이름들:
TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal. TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal. |
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실험적: Arm 4A: BDQ, Pa and Sutezolid (SZD) (800 mg)
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INH 300 mg will be administered as one tablet orally once daily.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
다른 이름들:
SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.
다른 이름들:
SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.
다른 이름들:
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실험적: Arm 4B: BDQ, Pa and SZD (1600 mg)
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INH 300 mg will be administered as one tablet orally once daily.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
다른 이름들:
SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.
다른 이름들:
SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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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
기간: Weeks 0, 1, 2, 3, 4 and 6
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for each experimental treatment arm compared to the SOC treatment arm. |
Weeks 0, 1, 2, 3, 4 and 6
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Difference in the cumulative proportion of participants having at least one new Grade 3 or higher adverse event (AE) by week 8 of treatment
기간: 8 weeks
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for each experimental treatment arm compared to the SOC treatment arm. |
8 weeks
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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2회 연속 측정에서 MGIT 액체 배양을 통해 배양 음성 상태로 측정한 결과 8주차까지 안정적인 가래 배양 전환이 발생한 참가자의 누적 비율입니다.
기간: 8주
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8주
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치료 첫 8주 동안 종방향 MGIT 액체 배양 측정에서 얻은 평균 log10 TTP 기울기.
기간: 0, 1, 2, 3, 4, 6, 8주차
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0, 1, 2, 3, 4, 6, 8주차
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치료 26주차까지 새로운 3등급 이상의 AE가 발생한 참가자의 누적 비율.
기간: 26주
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26주
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치료 8주차 이전에 어떤 이유로든 연구에서 제공한 항결핵제를 영구적으로 중단한 참가자의 누적 비율.
기간: 8주
|
8주
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치료 8주 전에 어떤 이유로든 최소 하나의 항결핵제를 3일 이상 영구적으로 중단하거나 일시적으로 중단한 참가자의 누적 비율입니다.
기간: 8주
|
8주
|
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치료 26주 전에 어떤 이유로든 적어도 하나의 항결핵제를 영구적으로 중단한 참가자의 누적 비율입니다.
기간: 26주
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26주
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치료 6주차에 안정적인 배양 전환이 이루어지고 8주차까지 새로운 3등급 이상의 AE가 발생하지 않은 복합입니다.
기간: 8주
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8주
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치료 시작 후 52주까지 지속적인 치료를 받은 참가자의 비율.
기간: 52주
|
52주
|
공동 작업자 및 조사자
협력자
수사관
- 연구 의자: Radojka Savic, PharmD, PhD, University of California
- 연구 의자: Kelly Dooley, MD, PhD, Vanderbilt University Medical Center
- 연구 의자: Gustavo Velásquez, MD, MPH, University of California
간행물 및 유용한 링크
일반 간행물
- Harrison LJ, Velasquez GE, Kempker RR, Imperial MZ, Nuermberger E, Dorman SE, Ignatius E, Granche J, Phillips PPJ, Furin J, Yang E, Foley C, Chiambah S, Rogers R, Van Grack A, Roa J, Shenje J, Nerette S, Kanyama C, Kyeyune RB, Mendoza-Ticona A, Murtaugh W, Foraida S, Goth M, Vernon A, Dooley KE, Savic RM. ACTG A5409 (RAD-TB): Study protocol for a phase 2 randomized, adaptive, dose-ranging, open-label trial of novel regimens for the treatment of pulmonary tuberculosis. Trials. 2025 Aug 15;26(1):291. doi: 10.1186/s13063-025-08973-w.
- Harrison L, Velasquez GE, Kempker RR, Imperial MZ, Nuermberger E, Dorman SE, Ignatius E, Granche J, Phillips PP, Furin J, Yang E, Foley C, Chiambah S, Rogers R, Van Grack A, Roa J, Shenje J, Nerette S, Kanyama C, Kyeyune RB, Mendoza-Ticona A, Murtaugh W, Foraida S, Goth M, Vernon A, Dooley KE, Savic RM. ACTG A5409 (RAD-TB): Study Protocol for a Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis. Res Sq [Preprint]. 2025 Mar 26:rs.3.rs-5931694. doi: 10.21203/rs.3.rs-5931694/v1.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 호흡기 감염
- 감염
- 호흡기 질환
- 폐 질환
- 그람 양성 세균 감염
- 세균 감염
- 세균 감염 및 진균증
- 방선균 감염
- 마이코박테리움 감염
- 결핵
- 결핵, 폐
- 유기 화학 물질
- 피리딘
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- 이종 사이 클릭 화합물, 융합 링
- Azoles
- 산, acyclic
- 카르 복실 산
- 다 환식 화합물
- 아미드
- 아민
- 이종 사이 클릭 화합물, 4 개 이상의 고리
- 리파 마이신
- 락탐, 마크로 사이 클릭
- 마크로 사이 클릭 화합물
- 피라진
- 아세트 아미드
- 아세테이트
- 옥사 졸리 디논
- 옥사 졸
- 히드라진
- 이소 니코틴산
- 산, 헤테로 사이 클릭
- 에틸렌 디아민
- 디아 민
- 폴리아민
- 리네졸리드
- 리팜핀
- 에탐부톨
- 이소니아지드
- 피라진아마이드
- Bedaquiline
- 프리 맨드
- PNU-100480
기타 연구 ID 번호
- A5409
- DOH-27-032024-5399 (기타 식별자: South African National Clinical Trial Registry (SANCTR))
- 38917 (레지스트리 식별자: DAIDS-ES Registry Number)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
Individual participant data that underlie results in the publication, after deidentification.
IPD 공유 기간
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
IPD 공유 액세스 기준
- 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.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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