Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort (INSPIRE-BDLL)

Fudan University

Status and phase: Enrolling; Phase 3

Conditions: Pulmonary Tuberculosis; Drug-resistant Tuberculosis; Rifampin-resistant Tuberculosis

Treatments: Drug: delamanid; Drug: bedaquiline; Drug: Clofazimine; Drug: linezolid; Drug: Levofloxacin

Study type: Interventional

Funder types: Other

Identifiers

NCT06649721

INSPIRE-BDLL

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 1 patient group

BDLL

Experimental group

Description:

6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen

Treatment:

Drug: Levofloxacin

Drug: linezolid

Drug: Clofazimine

Drug: bedaquiline

Drug: delamanid