Short-Course Regimen With Bedaquiline, Moxifloxacin and Pyrazinamide for Early Bactericidal Activity in Drug-Susceptible Tuberculosis

NCT07129629 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: Beams Study
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

\# Brief Summary This study aims to evaluate the early bactericidal activity (EBA), safety, and tolerability of 4-month short-course regimens containing bedaquiline, moxifloxacin, and pyrazinamide in patients with drug-susceptible tuberculosis. This is a prospective, randomized, controlled, multicenter study planned to enroll 45 rifampicin-susceptible tuberculosis patients, who will be randomized in a 1:1:1 ratio to the BZMD group (bedaquiline + pyrazinamide + moxifloxacin + delamanid), BZMH group (bedaquiline + pyrazinamide + moxifloxacin + isoniazid), and standard control group. Subjects in the test groups will receive 17 weeks (4 months) of group-specific treatment regimens, while subjects in the control group will receive 26 weeks (6 months) of standard HRZE regimen treatment. The primary endpoint is the change from baseline in log₁₀ colony-forming units (CFU) per milliliter of sputum specimen from Day 0 (pre-dose) to Day 14 of treatment (EBA CFU₀-₁₄), used to evaluate the early bactericidal activity of the drugs. Secondary endpoints include EBA CFU and EBA TTP (time to positive culture) at other time intervals, pharmacokinetic characteristics, sustained microbiological clearance rates, relapse rates, and safety indicators. The study will analyze the daily decline in log₁₀ CFU counts and daily increase in TTP using nonlinear mixed-effects models to reflect the bactericidal activity of the study regimens. This study will help provide more effective and safer short-course treatment options for Chinese patients with drug-susceptible tuberculosis, thereby improving treatment adherence and treatment success rates, and providing scientific evidence for optimizing short-course treatment regimens for drug-susceptible tuberculosis.

Conditions

Tuberculosis, Pulmonary; Drug-Susceptible Pulmonary Tuberculosis

Keywords

Bedaquiline; Moxifloxacin; Pyrazinamide; Early Bactericidal Activity; Drug-Susceptible Tuberculosis; Short-course regimen

Outcome Measures

Primary Outcomes (1)

• Early Bactericidal Activity CFU 0-14 (EBA CFU₀-₁₄)

  The change from baseline in log10 colony-forming units (CFU) per milliliter of sputum specimen from baseline (Day 0, pre-dose) to Day 14 of treatment. This measures the early bactericidal activity of the drug regimens over the first 14 days of treatment.

  Day 0 (baseline) to Day 14 of treatment

Secondary Outcomes (5)

• Early Bactericidal Activity CFU 0-2 (EBA CFU₀-₂)

  Day 0 to Day 2

• Early Bactericidal Activity CFU 0-7 (EBA CFU₀-₇)

  Day 0 to Day 7

• Early Bactericidal Activity TTP 0-14 (EBA TTP₀-₁₄)

  Day 0 (baseline) to Day 14 of treatment

• Sustained Microbiological Clearance Rate

  Week 17 (end of treatment)

• Safety - Grade 3 or Higher Adverse Events

  From enrollment through study completion, up to 52 weeks

Other Outcomes (8)

• Early Bactericidal Activity CFU 7-14 (EBA CFU₇-₁₄)

  Day 7 to Day 14 of treatment

• Early Bactericidal Activity TTP 0-2 (EBA TTP₀-₂)

  Day 0 (baseline) to Day 2 of treatment

• Early Bactericidal Activity TTP 0-7 (EBA TTP₀-₇)

  Day 0 (baseline) to Day 7 of treatment

Study Arms (3)

BZMD Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Delamanid)

EXPERIMENTAL

4-month short-course regimen. Intensive phase (8 weeks): Bedaquiline + Pyrazinamide + Moxifloxacin + Delamanid. Consolidation phase (9 weeks): Bedaquiline + Moxifloxacin + Delamanid. Total treatment duration 17 weeks followed by follow-up until week 38.

Drug: Bedaquiline (B); Drug: Moxifloxacin; Drug: Pyrazinamide (PZA); Drug: Delamanid (D)

BZMH Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Isoniazid)

EXPERIMENTAL

4-month short-course regimen. Intensive phase (8 weeks): Bedaquiline + Pyrazinamide + Moxifloxacin + Isoniazid. Consolidation phase (9 weeks): Bedaquiline + Moxifloxacin + Isoniazid. Total treatment duration 17 weeks followed by follow-up until week 38.

Drug: Bedaquiline (B); Drug: Moxifloxacin; Drug: Pyrazinamide (PZA); Drug: Isoniazid (H)

Standard Control Group (HRZE)

ACTIVE COMPARATOR

Standard 6-month regimen. Intensive phase (8 weeks): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol. Consolidation phase (18 weeks): Rifampicin + Isoniazid. Total treatment duration 26 weeks followed by follow-up until week 38.

Drug: Pyrazinamide (PZA); Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Ethambutol (E)

Interventions

Bedaquiline (B) DRUG

Bedaquiline tablets administered orally. Dosing: 400 mg once daily for the first 2 weeks, then 200 mg three times per week for weeks 3-17. Used in both experimental arms (BZMD and BZMH groups) as part of the 4-month short-course regimen for drug-susceptible tuberculosis treatment.

Also known as: BDQ

BZMD Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Delamanid); BZMH Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Isoniazid)

Moxifloxacin DRUG

Moxifloxacin 400 mg tablets administered orally once daily before or after meals throughout the entire treatment period (17 weeks). Used in both experimental arms (BZMD and BZMH groups) as part of the 4-month short-course regimen for drug-susceptible tuberculosis treatment.

Also known as: Mfx

BZMD Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Delamanid); BZMH Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Isoniazid)

Pyrazinamide (PZA) DRUG

Pyrazinamide tablets administered orally once daily in the morning during intensive phase (8 weeks). Dosing by weight: 1000 mg for 40.0-49.9 kg, 1500 mg for 50.0-70.9 kg, 2000 mg for ≥75.0 kg. Used in both experimental arms (BZMD and BZMH groups) and control group as part of tuberculosis treatment regimen.

Also known as: PZA

BZMD Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Delamanid); BZMH Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Isoniazid); Standard Control Group (HRZE)

Delamanid (D) DRUG

Delamanid tablets administered orally at 100 mg twice daily (total daily dose 200 mg) throughout the entire treatment period (17 weeks). Used only in the BZMD experimental arm as part of the 4-month short-course regimen for drug-susceptible tuberculosis treatment.

Also known as: Dlm

BZMD Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Delamanid)

Isoniazid (H) DRUG

Isoniazid tablets administered orally at 300 mg once daily in the morning throughout the entire treatment period. Used in the BZMH experimental arm (17 weeks) and in the standard control group (26 weeks) as part of tuberculosis treatment regimens.

Also known as: INH

BZMH Group (Bedaquiline + Moxifloxacin + Pyrazinamide + Isoniazid); Standard Control Group (HRZE)

Rifampicin (R) DRUG

Rifampicin tablets administered orally once daily in the morning throughout the entire treatment period (26 weeks). Dosing by weight: 450 mg for 40.0-49.9 kg, 600 mg for 50.0-70.9 kg and ≥75.0 kg. Used only in the standard control group as part of the 6-month standard tuberculosis treatment regimen.

Also known as: Rif

Standard Control Group (HRZE)

Ethambutol (E) DRUG

Ethambutol tablets administered orally during the intensive phase (8 weeks). Dosing by weight: 750 mg for 40.0-49.9 kg, 1000 mg for 50.0-70.9 kg and ≥75.0 kg. Used only in the standard control group as part of the 6-month standard tuberculosis treatment regimen.

Also known as: Emb

Standard Control Group (HRZE)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥18 years and ≤60 years
• Male or female
• Body weight 40-90 kg
• Capable of producing adequate sputum, with collection of at least 10ml overnight sputum
• Willing to participate in trial treatment and follow-up, with signed informed consent (legal guardian may sign for patients lacking civil capacity)
• Positive acid-fast bacilli smear microscopy of respiratory specimens (≥1+ according to WHO criteria) and positive rapid amplification test for Mycobacterium tuberculosis in respiratory specimens
• Rifampicin-susceptible based on molecular drug susceptibility testing or conventional drug susceptibility testing
• No anti-TB treatment for more than 3 days received within 6 months before the screening period
• Subjects whose imaging findings meet the diagnostic criteria for TB, as determined by the investigator
• Women of childbearing potential who have not undergone surgical sterilization must agree to use appropriate contraceptive methods

You may not qualify if:

• Evidence of concurrent extrapulmonary TB
• Subjects who have participated in other clinical studies within 8 weeks before the screening period
• Confirmed resistance of mycobacterium tuberculosis isolates to any of the following: Isoniazid, fluoroquinolones, revealed by molecular drug susceptibility testing
• Known allergy or intolerance to any study drug
• Patients who cannot receive oral therapy
• Abnormal liver function (alanine transaminase \[ALT\], alkaline phosphatase \[ALP\], or total bilirubin \[TBil\] exceeding 2 times the upper limit of normal) or known cirrhosis or known alcoholic hepatitis
• The hematology indicates white blood cells \<3.0×10⁹/L, or hemoglobin \<80 g/L, or platelets \<80×10⁹/L
• The estimated glomerular filtration rate (eGFR) is less than 60 mL/min/1.73 m²
• The blood electrolyte test indicates a baseline serum potassium level less than 3.5 mmol/L
• Subjects who have used drugs known to prolong the QTcF interval for more than 3 days within 30 days before the screening period (including but not limited to amiodarone, bisoprolol, chloroquine, chlorpromazine, cisapride, cyclobenzaprine, clarithromycin, digoxin, dofetilide, domperidone, ertapenem, ibutilide, levomethadone, methadone, pentamidine, quinidine, sotalol, sparfloxacin, thioridazine)
• Subjects with clinically significant ECG abnormalities as determined by the investigator, including but not limited to: baseline QTcF \>450 ms for males or \>470 ms for females, presence of second- or third-degree atrioventricular block, QRS duration \>120 ms
• Combined heart failure, coronary artery disease, myocardial infarction, ventricular hypertrophy, clinically significant arrhythmia, poorly controlled hypertension-related cardiovascular disease
• Patients with known QT prolongation syndrome or a family history thereof
• Subjects who have used any drug or substance known to be a strong inhibitor of cytochrome P450 enzymes within 30 days before the screening period (including but not limited to ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin, fluvoxamine, warfarin, rivaroxaban, and other novel oral anticoagulants)
• Subjects with known bleeding disorders or family history of bleeding disorders

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead
• Huashan Hospital: collaborator
• Guangzhou National Laboratory: collaborator

Related Publications (3)

• Paton NI, Cousins C, Suresh C, Burhan E, Chew KL, Dalay VB, Lu Q, Kusmiati T, Balanag VM, Lee SL, Ruslami R, Pokharkar Y, Djaharuddin I, Sugiri JJR, Veto RS, Sekaggya-Wiltshire C, Avihingsanon A, Sarin R, Papineni P, Nunn AJ, Crook AM; TRUNCATE-TB Trial Team. Treatment Strategy for Rifampin-Susceptible Tuberculosis. N Engl J Med. 2023 Mar 9;388(10):873-887. doi: 10.1056/NEJMoa2212537. Epub 2023 Feb 20.

  PMID: 36808186 BACKGROUND

• Cevik M, Thompson LC, Upton C, Rolla VC, Malahleha M, Mmbaga B, Ngubane N, Abu Bakar Z, Rassool M, Variava E, Dawson R, Staples S, Lalloo U, Louw C, Conradie F, Eristavi M, Samoilova A, Skornyakov SN, Ntinginya NE, Haraka F, Praygod G, Mayanja-Kizza H, Caoili J, Balanag V, Dalcolmo MP, McHugh T, Hunt R, Solanki P, Bateson A, Crook AM, Fabiane S, Timm J, Sun E, Spigelman M, Sloan DJ, Gillespie SH; SimpliciTB Consortium. Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial. Lancet Infect Dis. 2024 Sep;24(9):1003-1014. doi: 10.1016/S1473-3099(24)00223-8. Epub 2024 May 17.

  PMID: 38768617 BACKGROUND

• Tasneen R, Garcia A, Converse PJ, Zimmerman MD, Dartois V, Kurbatova E, Vernon AA, Carr W, Stout JE, Dooley KE, Nuermberger EL. Novel Regimens of Bedaquiline-Pyrazinamide Combined with Moxifloxacin, Rifabutin, Delamanid and/or OPC-167832 in Murine Tuberculosis Models. Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0239821. doi: 10.1128/aac.02398-21. Epub 2022 Mar 22.

  PMID: 35315690 BACKGROUND

Related Links

• World Health Organization Global Tuberculosis Report 2024 providing epidemiological background and current treatment recommendations for drug-susceptible tuberculosis.
• WHO consolidated guidelines on drug-susceptible tuberculosis treatment providing evidence-based recommendations for standard treatment regimens and management approaches that inform the study design and comparator arm selection.

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

bedaquiline; Moxifloxacin; Pyrazinamide; OPC-67683; Fumigant 93; Isoniazid; Protons; Rifampin; Ethambutol

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines

Central Study Contacts

sha wei Chief Physician and Doctoral Supervisor, MD&PhD

CONTACT

+86 65115006-2015; shfksw@126.com

liu yidian Study Coordinator Research Manager Deputy Investigator, MD

CONTACT

+86 65115006-2021; liuyidian115@139.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Not applicable - open-label study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician and Doctoral Supervisor

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 19, 2025
• Study Start: August 20, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share