Tuberculosis, Multidrug-Resistant
Conditions
Brief summary
The purpose of this study is to evaluate efficacy and safety of an oral bedaquiline-containing multidrug-resistant tuberculosis (MDR-TB) short-course regimen (SCR) compared to an oral SCR not including bedaquiline at the end of treatment in participants with pulmonary MDR-TB in China.
Interventions
DRUGBedaquiline
Bedaquiline uncoated tablets will be administered orally.
DRUGLevofloxacin
Levofloxacin filmcoated will be administered orally
DRUGLinezolid
Linezolid tablets will be administered orally
DRUGCycloserine
Cycloserine capsules will be administered orally.
DRUGClofazimine
Clofazimine capsules will be administered orally.
DRUGPyrazinamide
Pyrazinamide tablets will be administered orally.
DRUGProtionamide
Protionamide enteric-coated tablets will be administered orally.
Sponsors
Beijing Chest Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Has a positive sputum Mycobacterium tuberculosis culture from a test performed at screening * Has microbiological confirmation of rifampicin resistance by GeneXpert and to isoniazid (INH) via molecular drug-susceptibility testing (DST) showing katG mutation * Has a chest imaging result compatible with a diagnosis of pulmonary Tuberculosis (TB) * Agrees to use effective contraception during the 40-week study treatment phase. A female participant must be: of nonchildbearing potential; of childbearing potential and practicing effective methods of contraception during the 40-week study treatment phase * Is willing to undergo human immunodeficiency virus (HIV) testing
Exclusion criteria
* Has received prior treatment with bedaquiline * Has prior exposure to at least 1 second-line drug in the regimen for at least 4 weeks * Has any grade 3 or 4 laboratory abnormality as confirmed by a clinical expert * Has a known allergy or intolerance to bedaquiline or other drugs in the regimen * Is infected with a strain of nontuberculous mycobacteria * Is HIV-positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with a Favorable Treatment Outcome at the End of Treatment | At the end of treatment (Week 40) | Percentage of participants with a favorable treatment outcome at the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Treatment Success at the end of Treatment | At the end of treatment (Week 40) | Percentage of participants achieving treatment success at the end of treatment will be reported. Treatment success is achieved if participants completed their prescribed tuberculosis (TB) treatment; or if their last 3 culture results are negative by the end of treatment, these 3 cultures must be taken on separate visits and should be after the initial 6-month treatment period. |
| Percentage of Participants with a Modified Favorable Treatment Outcome at the end of Treatment and at 48 Weeks Post end of Treatment | At the end of treatment (Week 40) and at 48 weeks post end of treatment (Week 88) | Percentage of participants with a modified favorable treatment outcome at the end of treatment and at 48 weeks post end of treatment will be reported. A participant's treatment outcome will be classified as modified favorable if their last 2 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 2 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment. |
| Percentage of Participants Experiencing All-cause Mortality | Up to Week 88 | Percentage of participants experiencing all-cause mortality will be reported. |
| Percentage of Participants with a Favorable Treatment Outcome at 48 Weeks Post the End of Treatment | At 48 weeks post the end of treatment (Week 88) | Percentage of participants with a favorable treatment outcome at 48 weeks post the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment. |
| Percentage of Participants Experiencing TEAEs | From Week 1 up to Week 88 | Percentage of participants experiencing TEAEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study. |
| Percentage of Participants with TB Relapses and Re-infections During the Treatment-free Follow-up Phase | During the treatment-free follow-up phase (Up to 48 weeks) | Percentage of participants with TB relapses and re-infections during the treatment-free follow-up phase will be reported. |
| Percentage of Participants Whose Isolates Develop Resistance to Bedaquiline and Other Drugs Used in the Regimen | Up to Week 88 | Percentage of participants whose isolates develop resistance to bedaquiline and other drugs used in the regimen will be reported. |
| Percentage of Participants Experiencing Grade 3 or Greater Treatment-emergent Adverse Events (TEAEs) During Study Treatment and Follow-up | During study treatment and follow-up (From Week 1 up to Week 88) | Percentage of participants experiencing grade 3 or greater TEAEs during study treatment and follow-up will be reported. An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study. An assessment of severity grade will be made using the following 5 general categorical descriptors based on division of acquired immunodeficiency syndrome (AIDS) grading for AE severity assessment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death. |
Countries
China
Contacts
Primary ContactJingtao Gao, PhD
Outcome results
None listed