Innovating(IN) Shorter(S), All- Oral, Precised(P), Individualized(I) Treatment Regimen(RE) for Rifampicin Resistant Tuberculosis(INSPIRE-TB)

NCT05081401 | Recruiting Phase 3 DMC

• 1 other identifier: INSPIRE-TB
• Study Type: interventional
• Target: 1,050
• Locations: 1 country
• Sites: 5

Brief Summary

The INSPIRE-TB study is a pragmatic, multicentre, randomised, controlled, non-inferiority open-label trial to evaluate the efficacy and safety of seven 9-month oral regimens compared to a 9-month standard of care (SOC) regimen in RR-TB participants susceptible to fluoroquinolones, and a bedaquiline-containing 9-month oral regimen compared to a 20-month conventional regimen in RR-TB participants resistant to fluoroquinolones

Conditions

Multidrug Resistant Tuberculosis; Rifampicin Resistant Tuberculosis; Pre-XDR-TB

Keywords

multidrug resistant tuberculosis; shorter treatment; all-oral regimen; PZA sensitivity

Outcome Measures

Primary Outcomes (1)

• a favorable outcome at the end of study

  A favorable outcome is defined by the absence of previous unfavorable, and the last two culture results are negative. These two cultures must be taken from respiratory samples collected on separate visits at least 7 days apart. The latest culture sample should be collected between month 21 and 23.

  at 21 months after randomization

Secondary Outcomes (6)

• The median time to sputum culture conversion

  at 21 months after randomization

• The proportion of participants with grade 3 or higher AEs, SAEs

  at 21 months after randomization

• All-cause mortality and treatment relevant mortality

  at 21 months after randomization

• The proportion of participants with treatment relevant SAEs

  at 21 months post-randomization

• The proportion of participants with grade 3 or higher QTc prolongation

  at 21 months after randomization

Study Arms (10)

A-SOC

ACTIVE COMPARATOR

The control arm for fluroquinolones susceptible participants is the current standard of care oral regimen for RR-TB recommended by Chinese national guidelines. The SOC regimen comprise one or two group A drugs(bedaquiline or linezolid, moxifloxacin or levofloxacin) and one group B drug(clofazimine or cycloserine) along with other companion drugs.

Combination Product: Bdq(Lzd)+Lfx(Mfx)+Cfz(Cs)+Pto+E+H+Z

A1

EXPERIMENTAL

The experimental A1 arm in fluroquinolones susceptible participants is a 9-month regimen consisted of bedaquiline, linezolid, fluroquinolones(moxifloxacin or levofloxacin), cycloserine, clofazimine.

Combination Product: A1

A2a

EXPERIMENTAL

The experimental A2a arm in fluroquinolones susceptible participants is a 9-month regimen consisted of bedaquiline, linezolid, fluroquinolones(moxifloxacin or levofloxacin), cycloserine, pyrazinamide. The dosage of linezolid is 600mg daily for 9 months.

Combination Product: A2a

A2b

EXPERIMENTAL

The experimental A2b arm in fluroquinolones susceptible participants is a 9-month regimen consisted of bedaquiline, linezolid, fluroquinolones(moxifloxacin or levofloxacin), cycloserine, pyrazinamide. The dosage of linezolid is 600mg daily for 2 months.

Combination Product: A2b

A2c

EXPERIMENTAL

The experimental A2c arm in fluroquinolones susceptible participants is a 9-month regimen consisted of bedaquiline, linezolid, fluroquinolones(moxifloxacin or levofloxacin), cycloserine, pyrazinamide. The dosage of linezolid is 600mg daily for 2 months and then 300mg daily for 7 months.

Combination Product: A2c

A3

EXPERIMENTAL

The experimental A3 arm in fluroquinolones susceptible participants is a 9-month regimen consisted of bedaquiline, linezolid, fluroquinolones(moxifloxacin or levofloxacin), clofazimide, pyrazinamide.

Combination Product: A3

A4

EXPERIMENTAL

The experimental A4 arm in fluroquinolones susceptible participants is a 9-month regimen consisted of bedaquiline, fluroquinolones(moxifloxacin or levofloxacin), clofazimide, cycloserine, pyrazinamide.

Combination Product: A4

A5

EXPERIMENTAL

The experimental A4 arm in fluroquinolones susceptible participants is a 9-month regimen consisted of fluroquinolones(moxifloxacin or levofloxacin), linezolid, clofazimide, cycloserine, pyrazinamide.

Combination Product: A5

B-SOC

ACTIVE COMPARATOR

In fluroquinolones resistant participants, the comparator is a locally approved standard of care long regimen which is consistent with local guidelines for treatment of RR-TB in China and WHO recommendations. The control arm contain bedaquiline, cycloserine, clofazimine, and linezolid. Treatment duration is 20 months, with a 6-month intensive phase and a 14-month continuation phase.

Combination Product: B-SOC

B1

EXPERIMENTAL

In fluroquinolones resistant participants, the arm B1 is a 9-month treatment regimen with a combination of five drugs: bedaquiline, cycloserine, clofazimine, linezolid, pyrazinamide.

Combination Product: B1

Interventions

Bdq(Lzd)+Lfx(Mfx)+Cfz(Cs)+Pto+E+H+Z COMBINATION_PRODUCT

A-SOC: 4Bdq(Lzd)+Lfx(Mfx)+Cfz(Cs)+Pto+E+H+Z/5Lfx(Mfx)+Cfz(Cs)+E+Z During the intensive phase: Bedaquiline(Linezolid);Levofloxacin(Moxifloxacin) All treatment is taken orally

A-SOC

A1 COMBINATION_PRODUCT

9Bdq(6m)+Fq+Lzd+Cs+Cfz

A1

A2a COMBINATION_PRODUCT

9Bdq(6m)+Fq+Lzd(600mg)+Cs+Z

A2a

A2b COMBINATION_PRODUCT

9Bdq(6m)+Fq+Lzd(2m)+Cs+Z

A2b

A2c COMBINATION_PRODUCT

9Bdq(6m)+Fq+Lzd(600mg-300mg)+Cs+Z

A2c

A3 COMBINATION_PRODUCT

9Bdq(6m)+Fq+Lzd+Cfz+Z

A3

A4 COMBINATION_PRODUCT

9Bdq(6m)+Fq+Cfz+Cs+Z

A4

A5 COMBINATION_PRODUCT

9Fq+Lzd+Cfz+Cs+Z

A5

B-SOC COMBINATION_PRODUCT

6Bdq+Lzd+Cs+Cfz/14Lzd+Cfz+Cs

B-SOC

B1 COMBINATION_PRODUCT

9Bdq(6m)+Lzd+Cs+Cfz+Z

B1

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 16-75 years with weight over 30kg, regardless of HIV status;
• Pulmonary TB with rifampicin resistance diagnosed with either WHO-approved rapid molecular diagnostic test or phenotype drug susceptibility test (within 60 days prior to randomisation) ;
• Signed informed consent form (ICF).

You may not qualify if:

• Known allergies, hypersensitivity, or contraindication to any of the study drugs as described in additional material;
• Participants combined with central nervous system TB, tuberculous osteomyelitis or arthritis, hematogenous disseminated pulmonary TB;
• Patients known to be pregnant or breastfeeding at the time of enrollment;
• Patients who have received second-line MDR-TB treatment for 14 days or more prior to enrollment;
• Patients in critical condition and expected survival is estimated by physician to be less than 12 weeks.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (5)

Guiyang Public Health Treatment Center

Guiyang, Guizhou, China

RECRUITING

People's Hospital of Qiandongnan

Kaili, Guizhou, China

RECRUITING

The Third People's Hospital of Liupanshui

Liupanshui, Guizhou, China

RECRUITING

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, China

RECRUITING

Huashan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

A(2)C

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Wenhong Zhang, PHD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Sun, Dr.

CONTACT

(086)15921403893; feng.sun@nmcid.org.cn

Yang Li, Dr.

CONTACT

(086)18817583793; lalaliy@sina.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: Director of Division of Infectious Diseases

Study Record Dates

• First Submitted: October 5, 2021
• First Posted: October 18, 2021
• Study Start: May 23, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)