Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort (NCT06649721) — China Trial Details

Condition(s) studied

Drug-resistant TuberculosisPulmonary TuberculosisRifampin-resistant Tuberculosis

Investigational drug(s) / intervention(s)

bedaquilinedelamanidlinezolidLevofloxacinClofazimine

bedaquiline: 400 milligrams (mg) daily for 2 weeks(w), then 200mg three times a week for 22 weeks (w)

delamanid: * for participants weighing up to 33.9 kilograms (kg): 50mg two times a day for 24w * for participants weighing 34kg or above: 100mg two times a day for 8w, then 200mg daily for 16w

linezolid: * for participants weighing up to 33.9kg: 450mg daily; * for participants weighing 34kg or above: 600mg daily; for 24w if a negative culture is obtained from sputum collected at 16w, or else for 36w

Levofloxacin: Only for participants with confirmed fluoroquinolone-susceptible TB or unknown fluoroquinolone susceptibility: * for participants weighing up to 33.9kg: 500mg daily * for participants weighing 34kg to 49.9kg: 750 daily * for participants weighing 50kg or above: 1000mg daily for 24w if a negative culture is obtained from sputum collected at 16w, or else for 36w

Clofazimine: Only for participants with confirmed fluoroquinolone-resistant TB or unknown fluoroquinolone susceptibility: 100mg daily, for 24w if a negative culture is obtained from sputum collected at 16w, or else for 36w

Study summary

This is an investigational, prospective, multicenter, single-arm, open label trial. The goal of this clinical trial is to evaluate the efficacy and safety of a 6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), or BDLLfxC regimen, to treat rifampin-resistant pulmonary tuberculosis (RR-TB) in Chinese teenagers and adults (aged 12 years or above). The main questions it aims to answer are:

* Is BDLLfxC regimen effective to treat RR-TB in Chinese participants?
* Is BDLLfxC regimen safe in Chinese RR-TB participants? Participants will take BDLLfxC regimen to treat their RR-TB. There will be no additional hospital visits, laboratory tests or radiological examinations other than routine clinical practice.

Eligibility

Sex

ALL

Min age

12 Years

Max age

—

Healthy volunteers

No

Inclusion Criteria: * Participants are willing to sign informed consent of this trial, those without capacity for civil conduct need their legal guardian to sign * Participants (and their legal guardian if applicable) are willing to cooperate to complete all trial procedures * Male or female, 12 years or older, weight ≥ 30kg * Confirmed pulmonary tuberculosis with resistance to rifampin by phenotypic or genotypic susceptibility testing within 3 months, and must be re-confirmed by sputum culture sampled at trial inclusion * Women with childbearing potential should not be pregnant, confirmed by a volunteered negative pregnancy test, and are willing to use effective contraceptive method from giving consent to 3 months after study treatment * Men with childbearing potential must be willing to use condom or other effective contraceptive methods to avoid their sex partners from being pregnant * Women in breastfeeding period must be willing to discontinue breastfeeding from giving consent to 3 months after study treatment * Participants are willing to take HIV test, and willing to take appropriate antiretroviral therapy if positive Exclusion Criteria: * Previously use of Bedaquiline or Delamanid for at least 28 days * Concomitant hematogenous disseminated tuberculosis, or severe pulmonary tuberculosis in investigator's opinion (including tuberculosis of the digestive system, osteoarticular tuberculosis or tuberculous meningitis) * Currently using any drug that has been prohibited in the protocol * History of allergic action to any of the study drugs * Currently participating in any other clinical trials * Cardiovascular risk at screening: (1) QTcF more than 480 milliseconds (ms); (2) History of clinically significant arrythmia, and at investigator's opinion, participation in this study will increase the risk; (3) Decompensated heart failure; (4) Grade 3 high blood pressure and the goals of treatment have not been reached; (5) Abnormal thyroid function; (6) Abnormal serum Ca, Mg or K level; (7) Other conditions with cardiovascular risks in investigator's opinion. * History of optic neuropathy or peripheral neuropathy, and the investigator considers that the condition may progress or deteriorate by participating in the study, or inappropriate to participate * Hepatic disorders at screening: (1) Active viral hepatitis: HBsAg positive or HBV DNA \>1000 CPs/mL, with elevated AST or ALT or HCV RNA positive; (2) Decompensated cirrhosis * Renal disorders at screening: (1) Unstable or rapidly progressive renal disease; (2) Moderate / severe renal disfunction or end-stage renal disease (eGFR\< 60 mL/min/1.73 m2); (3) Serum creatinine ≥133 μmol/L(1.5 mg/mL) in men, or ≥124 μmol/L (1.4 mg/mL) in women * Other abnormal laboratory test: (1) Hemoglobin \< 8.0g/dL; (2) Platelet \<75,000/mm3; (3) Absolute neutrophil count \<1000/mm3; (4) Aspartate transaminase (AST) or alanine aminotransferase (ALT) \>3×upper limit of normal (ULN); (5) Total bilirubin (TBil) \>2×ULN, or \>1.5×ULN together with abnormal AST or ALT; (6) Albumin \<30g/L * The investigator considers that the participant is not able to complete the study process, or the participation is not safe.

Primary outcome measure(s)

Proportion of participants with favorable outcomes in both treatment and follow-up period — Up to 72 weeks after start of treatment
Favorable outcome in treatment period (up to 28 weeks after start of treatment): a participant's outcome will be defined as "favorable" if it meets any of the following below and has not been defined as "unfavorable" before, 1. . Cured: complete at least 80% of total required dose per protocol, with negative culture results of last two sputum samples (collected 14 days apart) ; 2. . Treatment completed: complete at least 80% of total required dose per protocol, with NO negative culture results of last two sputum samples (collected 14 days apart); Favorable outcome in follow-up period (from end of treatment to 72 weeks after start of treatment): a participant's outcome will be defined as "favorable" if it meets any of the following below and has not been defined as "unfavorable" before, (1). Cured: sputum culture negative at 72 weeks from start of treatment; (2). Culture negative when last seen: loss to follow-up before 72 weeks, with negative sputum culture when last seen.

Trial sites (34)

Facility	City	Region
Anhui Chest Hospital	Hefei	Anhui
The 8th Medical Center of Chinese PLA General Hospital	Beijing	Beijing Municipality
The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
The Fourth People's Hospital of Nanning	Nanning	Guangxi
Liupanshui Third People's Hospital	Liupanshui	Guizhou
Hebei Chest Hospital	Shijiazhuang	Hebei
The Fifth Hospital of Shijiazhuang	Shijiazhuang	Hebei
Infectious Disease Hospital of Heilongjiang Province	Harbin	Heilongjiang
Jiamusi Tuberculosis Hospital(Jiamusi Cancer Hospital)	Jiamusi	Heilongjiang
Harbin Chest Hospital	Harbin	Helongjiang
Luoyang Center Hospital	Luoyang	Henan
The First Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
Henan Chest Hospital	Zhengzhou	Henan
Henan Infectious Disease Hospital	Zhengzhou	Henan
Wuhan Pulmonary Hospital，Wuhan Tuberculosis Prevention and Control Institute	Wuhan	Hubei
Changsha Central Hospital	Changsha	Hunan
Hulunbuir Infectious Disease Hospital	Hulunbuir	Inner Mongolia
The Second Hospital of Nanjing	Nanjing	Jiangsu
Jiangxi Chest Hospital	Nanchang	Jiangxi
Infectious Disease Hospital of Changchun	Changchun	Jilin
Jilin Tuberculosis Hospital	Jilin City	Jilin
Shenyang Chest Hospital	Shenyang	Liaoning
Xi'an Chest Hospital	Xi'an	Shaanxi
Shandong Public Health Clinical Center, Shandong University	Jinan	Shandong
Linyi People Hospital	Linyi	Shandong
Qingdao Chest Hospital	Qingdao	Shandong
Weifang No.2 People's Hospital	Weifang	Shandong
Yantai Qishan Hospital	Yantai	Shandong
Shanxi Medical University Affiliated Chest Hospital	Taiyuan	Shanxi
Public Health Clinical Center of Chengdu	Chengdu	Sichuan
Tianjin Haihe Hospital	Tianjin	Tianjin Municipality
Wenzhou Central Hospital	Wenzhou	Zhejiang
Beijing Chest Hospital	Beijing	China
Huashan Hospital	Shanghai	China

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