A PAN-USR TB Multi-Center Trial

NCT06905522 | Recruiting Phase 3 FDA Drug

• 1 other identifier: SMART-C2405002
• Study Type: interventional
• Target: 610
• Locations: 1 country
• Sites: 3

Brief Summary

Tuberculosis (TB) remains a major public health issue and one of the top ten causes of death from a single infectious disease worldwide. China is among the countries with the highest TB burden, ranking third globally for total TB cases and second for drug-resistant TB cases. PAN-TB is an innovative concept in TB treatment, aiming to develop a universal regimen effective for all forms of active TB, including both drug-susceptible and drug-resistant strains. The primary goal of the PAN-TB regimen is to simplify the treatment process, reduce costs, and improve treatment success rates. The ideal Target Regimen Profile (TRP) for PAN-TB includes superior efficacy compared to standard treatment for non-drug-resistant TB, a reduced treatment duration from the current 4-6 months to 2-3 months, and improved safety and tolerability. This project aims to explore a new ultra-short-course treatment regimen for both drug-sensitive (DS-TB) and drug-resistant TB (MDR/RR-TB), which aligns with the latest trends in TB treatment both domestically and internationally. The regimen also has significant practical implications for enhancing treatment efficacy and reducing patient burden. Furthermore, the study will explore the identification of new biomarkers closely linked to treatment outcomes over the course of full-cycle therapy.

Conditions

Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Unfavorable outcomes

  Percentage of patients with unfavorable outcomes (failure, treatment interruption, death, loss to follow-up, re-treatment, recurrence) at 12 months (52 weeks) after randomization

  12 months (52 weeks)

• Safety

  Percentage of patients who have treatment interruption due to any reason or died within 2 months (9 weeks) after randomization

  2 months (9 weeks)

Secondary Outcomes (9)

• Sputum culture conversion rate

  2 months (9 weeks) after randomization

• Unfavorable outcomes (short-term)

  6 months (26 weeks) after randomization

• Unfavorable outcomes (mid-term)

  18 months (78 weeks) after randomization

• Time to sputum culture conversion

  Median time

• Serious adverse events or grade 3 or higher adverse events (short-term)

  12 months (52 weeks) after randomization

Study Arms (4)

Drug-susceptible TB (A1)

EXPERIMENTAL

2 months (9 weeks) BLSZ regimen: The treatment involves the use of bedaquiline (B), linezolid (L), sitafloxacin (S), and pyrazinamide (Z) throughout the entire process. At the end of 2 months (9 weeks) of treatment, if the sputum smear is still positive or if clinical symptoms have not improved, the treatment duration can be extended to 13 weeks. After the extended treatment period (3 months or 13 weeks), if the sputum smear remains positive or if clinical symptoms have not been relieved, the patient should be switched to the standard treatment regimen, and the subject should be withdrawn from the study.

Drug: Bedaquiline (B); Drug: Sitafloxacin (S); Drug: Linezolid (L); Drug: Pyrazinamide (Z)

Drug-resistant TB (A2)

EXPERIMENTAL

2 months (9 weeks) BLSZ regimen: The treatment involves the use of bedaquiline (B), linezolid (L), sitafloxacin (S), and pyrazinamide (Z) throughout the entire process. At the end of 2 months (9 weeks) of treatment, if the sputum smear is still positive or if clinical symptoms have not improved, the treatment duration can be extended to 13 weeks. After the extended treatment period (3 months or 13 weeks), if the sputum smear remains positive or if clinical symptoms have not been relieved, the patient should be switched to the standard treatment regimen, and the subject should be withdrawn from the study.

Drug: Bedaquiline (B); Drug: Sitafloxacin (S); Drug: Linezolid (L); Drug: Pyrazinamide (Z)

Drug-susceptible TB (B)

ACTIVE COMPARATOR

2HRZE/4HR (26 weeks): Four drugs-isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E)-are used during the first 2 months of the intensive phase. This is followed by 4 months of consolidation treatment, during which only isoniazid and rifampicin are used.

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

Drug-resistant TB (C)

ACTIVE COMPARATOR

6 months (26 weeks) of BPaLM: The treatment involves the use of bedaquiline (B), pretomanid (Pa), linezolid (L), and moxifloxacin (M) throughout the entire course. If the sputum culture remains positive at 4 months, or if clinical symptoms are not relieved by 6 months, or if chest CT results show worsening at 6 months, the treatment may be extended to 9 months. If the patient chooses to withdraw from the study at 6 months, they are allowed to do so.

Drug: Bedaquiline (B); Drug: Linezolid (L); Drug: Moxifloxacin (M); Drug: Pretomanid (Pa)

Interventions

Bedaquiline (B) DRUG

The initial dose of bedaquiline is 400 mg daily for 2 weeks, followed by 200 mg three times a week.

Drug-resistant TB (A2); Drug-resistant TB (C); Drug-susceptible TB (A1)

Sitafloxacin (S) DRUG

200mg once daily

Drug-resistant TB (A2); Drug-susceptible TB (A1)

Linezolid (L) DRUG

600mg once daily

Drug-resistant TB (A2); Drug-resistant TB (C); Drug-susceptible TB (A1)

Pyrazinamide (Z) DRUG

20-30 mg/kg/day; 1000 mg for patients weighing \<50 kg, 1500 mg for patients weighing ≥50 kg but \<75 kg, and 2000 mg for patients weighing ≥75 kg.

Drug-resistant TB (A2); Drug-susceptible TB (A1); Drug-susceptible TB (B)

Isoniazid (H) DRUG

4-6 mg/kg once daily, 300 mg once daily

Drug-susceptible TB (B)

Rifampicin (R) DRUG

8-12 mg/kg once daily, 450 mg for patients weighing \<50 kg, 600 mg for patients weighing ≥50 kg but \<75 kg, and 750 mg for patients weighing ≥75 kg.

Drug-susceptible TB (B)

Ethambutol (E) DRUG

15-25 mg/kg once daily, 750 mg once daily

Drug-susceptible TB (B)

Moxifloxacin (M) DRUG

400mg once daily

Drug-resistant TB (C)

Pretomanid (Pa) DRUG

200mg once daily

Drug-resistant TB (C)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range from 18 to 65 years old, regardless of gender;
• Clinical symptoms and/or pulmonary imaging (chest X-ray or chest CT) support the diagnosis of active pulmonary tuberculosis;
• Microbiological testing (molecular or phenotypic) confirms the presence of Mycobacterium tuberculosis, whether resistant to rifampicin or not; Recommend using respiratory specimens for GeneXpert MTB/RIF testing;
• Voluntarily sign the informed consent form for participating in this project and be able and willing to accept follow-up visits;
• Willing to undergo HIV testing;
• Willing to preserve samples including DNA;
• For women with fertility, they have a negative serum or urine pregnancy test within 3 days before enroll the study and be willing to use effective contraceptive measures during the study period. Female subjects without fertility must have records of menopause, hysterectomy, bilateral oophorectomy, or bilateral tubal ligation. Acceptable forms of contraception include condoms, intrauterine devices, cervical caps with spermicides, and diaphragm with spermicides.

You may not qualify if:

• Prior to this study, patients who were diagnosed with active pulmonary tuberculosis and had received anti-tuberculosis treatment (including first-line and second-line anti-tuberculosis drugs);
• Intolerance or allergy to any investigational drug (i.e., bedaquiline, linezolid, fluoroquinolones \[including moxifloxacin, sitagliptin\], pyrazinamide);
• Resistance to any investigational drug (i.e., bedaquiline, linezolid, fluoroquinolones \[including moxifloxacin, sitagliptin\], pyrazinamide). The following detection methods can be used: tNGS or other drug sensitivity testing methods (such as GeneXpert MTB/XDR, dissolution curve method, phenotypic drug sensitivity, etc.);
• Suffering from hematogenous disseminated tuberculosis or coexisting with extrapulmonary tuberculosis (as specified in this study, the scope of pulmonary tuberculosis includes: simple pulmonary tuberculosis, pulmonary tuberculosis + tuberculous pleurisy/bronchial tuberculosis/mediastinal lymph node tuberculosis. Extrapulmonary tuberculosis refers to tuberculosis other than the chest-related types mentioned above);
• Presence of non-tuberculous mycobacteria or other microbial lung infections that affect treatment outcomes;
• Simultaneously using drugs that affect the efficacy of this study or have contraindications for combination therapy;
• Use of any immunosuppressive medication or systemic glucocorticoids for more than 2 weeks before screening;
• Any medication currently used or planned to be used that is known to significantly prolong the QTc interval, including but not limited to: amiodarone, amitriptyline, chloroquine, chlorpromazine, cisapride, dipyridamole, itraconazole, procaine, quinidine, or sotalol;
• Uncontrolled blood sugar in diabetes, with no likelihood of improving blood sugar status according to the judgment of the researchers;
• HIV positive;
• Coexisting with severe autoimmune diseases, severe liver and kidney dysfunction, psychiatric disorders, hematological disorders, or malignant tumors;
• Laboratory parameters within 14 days prior to recruitment: (1) Serum AST and ALT levels ≥ 3 times the upper limit of normal (ULN); (2) Blood creatinine ≥ 2 times ULN; (3) Hemoglobin ≤ 70 g/L; (4) Platelet count ≤ 50 × 10\^9/L; (5) Blood potassium levels are ≥ 5.5 mmol/L or ≤ 3.5 mmol/L;
• Women who are pregnant or breastfeeding;
• Weight \<30 kg, or ≥90 kg;
• The patient has participated in clinical trials of other drugs within the past 3 months during the screening period;

Sponsors & Collaborators

• Shenzhen Third People's Hospital: lead
• First Affiliated Hospital of Zhejiang University: collaborator
• Beijing Chest Hospital of Capital Medical University: collaborator
• Shenyang Tenth People's Hospital: collaborator
• The Sixth People's Hospital of the Xinjiang Uygur Autonomous Region: collaborator
• The Fourth Hospital of Inner Mongolia Autonomous Region: collaborator
• Guizhou Aerospace Hospital: collaborator

Study Sites (3)

Beijing Chest Hospital of Capital Medical University

Beijing, China

RECRUITING

Shenzhen Third People's Hospital

Shenzhen, China

RECRUITING

The Sixth People's Hospital of the Xinjiang Uygur Autonomous Region

Ürümqi, China

RECRUITING

Related Publications (7)

• 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 RESULT

• Conradie F, Bagdasaryan TR, Borisov S, Howell P, Mikiashvili L, Ngubane N, Samoilova A, Skornykova S, Tudor E, Variava E, Yablonskiy P, Everitt D, Wills GH, Sun E, Olugbosi M, Egizi E, Li M, Holsta A, Timm J, Bateson A, Crook AM, Fabiane SM, Hunt R, McHugh TD, Tweed CD, Foraida S, Mendel CM, Spigelman M; ZeNix Trial Team. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis. N Engl J Med. 2022 Sep 1;387(9):810-823. doi: 10.1056/NEJMoa2119430.

  PMID: 36053506 RESULT

• Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: 10.1056/NEJMoa2117166.

  PMID: 36546625 RESULT

• Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Moodliar R, Dodd M, Solodovnikova V, Liverko I, Rajaram S, Rassool M, McHugh T, Spigelman M, Moore DA, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL team. Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. Lancet Respir Med. 2024 Feb;12(2):117-128. doi: 10.1016/S2213-2600(23)00389-2. Epub 2023 Nov 16.

  PMID: 37980911 RESULT

• Zhang Y, Shi W, Zhang W, Mitchison D. Mechanisms of Pyrazinamide Action and Resistance. Microbiol Spectr. 2014 Aug;2(4):MGM2-0023-2013. doi: 10.1128/microbiolspec.MGM2-0023-2013.

  PMID: 26104205 RESULT

• Zhang Y, Chiu Chang K, Leung CC, Wai Yew W, Gicquel B, Fallows D, Kaplan G, Chaisson RE, Zhang W. 'Z(S)-MDR-TB' versus 'Z(R)-MDR-TB': improving treatment of MDR-TB by identifying pyrazinamide susceptibility. Emerg Microbes Infect. 2012 Jul;1(7):e5. doi: 10.1038/emi.2012.18. Epub 2012 Jul 25.

  PMID: 26038418 RESULT

• Fu L, Zhang X, Xiong J, Sun F, Weng T, Li Y, Zhang P, Li H, Yang Q, Cai Y, Liang H, Chen Q, Wang Z, Liu L, Chen X, Zhang W, Deng G. Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study. Int J Infect Dis. 2023 Oct;135:101-108. doi: 10.1016/j.ijid.2023.08.001. Epub 2023 Aug 10.

  PMID: 37567554 RESULT

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

bedaquiline; sitafloxacin; Linezolid; Pyrazinamide; Isoniazid; Protons; Rifampin; Ethambutol; Moxifloxacin; pretomanid

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)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Hydrazines; 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; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Central Study Contacts

Professor Lu

CONTACT

+86 18930811818; lushuihua66@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: April 1, 2025
• Study Start: June 18, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 1, 2025

Record last verified: 2025-11

Locations

CN (3)