Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03086486
Other study ID # ZeNix (B-Pa-L) NC-007
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date November 21, 2017
Est. completion date February 8, 2022

Study information

Verified date June 2023
Source Global Alliance for TB Drug Development
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To evaluate the efficacy, safety and tolerability of various doses and durations of linezolid plus bedaquiline and pretomanid after 26 weeks of treatment in participants with either pulmonary XDR-TB, pre-XDR-TB, or treatment intolerant or non-responsive MDR-TB.


Description:

A phase 3, multi-center, partially-blinded, randomized clinical trial in 4 parallel treatment groups. Bedaquiline and pretomanid treatment will not be blinded. Linezolid treatment dose and duration will be double-blinded. Participants will have a screening period of up to 14 days and will be randomized to receive one of the 4 active treatment arms. Participants will be randomized to one of the 4 regimens in a 1:1:1:1 ratio, using an interactive voice and web response system (IXRS) which will utilize a randomization system using stratification with a random element to allocate participants evenly across the arms by HIV status and type of TB. Each participant will receive 26 weeks of treatment. If participant's week 16 sputum sample is culture positive between the week 16 and week 26 treatment visits and their clinical condition suggests they may have an ongoing TB infection, Investigator may consider extending current treatment to 39 weeks. If the culture results between week 16 and week 26 are contaminated, missing or considered an isolated positive without clinical significance, available culture results should be used to make this decision. All decisions regarding treatment extension should be discussed with and approved by, in consultation with the Sponsor Medical Monitor before implementation. The treatment may also require modification due to toxicities. All dose modifications should be discussed with the Sponsor Medical Monitor prior to implementation, unless a pause or dose reduction is required urgently for safety concerns. Participants will be followed for 78 weeks after end of treatment.


Recruitment information / eligibility

Status Completed
Enrollment 181
Est. completion date February 8, 2022
Est. primary completion date February 15, 2021
Accepts healthy volunteers No
Gender All
Age group 14 Years and older
Eligibility Inclusion Criteria: - Male or female, aged 14 years or older. - One of the following with documentation of culture positive or molecular test within 3 months of screening: - XDR-TB defined as resistance to rifamycins, a fluoroquinolone AND an injectable OR - Pre-XDR-TB with defined as resistance to rifamycins, and to a fluoroquinolone OR an injectable OR - MDR-TB with resistance to rifamycins, and either non-responsive or non-tolerant to current treatment. - Of non-childbearing potential or willing to practice effective birth control methods. - Complete informed consent form. Exclusion criteria: - Karnofsky score < 60 at screening. - Body mass index (BMI) < 17 kg/m2 - Participants who are expected to require a surgical procedure (for Pulmonary TB). - Any risk factor for QT prolongation - Pregnant or breast-feeding - Any planned contraindicated medicines or received more than 2 weeks of bedaquiline, linezolid or delamanid prior to first dose of IMP. - A peripheral neuropathy of Grade 3 or 4, according to DMID. Or, participants with a Grade 1 or 2 neuropathy which is likely to progress/worsen over the course of the study, in the opinion of the Investigator - Any of the following lab toxicities/abnormalities: - Viral load >1000 copies/mL (Unless newly diagnosed HIV and not yet on ART who otherwise qualify for participation); - CD4+ count < 100 cells/µL (HIV positive participants); - Serum potassium less than the lower limit of normal for the laboratory; - Hemoglobin < 9.0 g/dL or 90g/L; - Platelets <100,000/mm3 or < 100 x 10^9/L - Absolute neutrophil count (ANC) < 1500/ mm3 or < 1.5 x 10^9/L - Aspartate aminotransferase (AST) and Alanini aminotransferase (ALT) Grade 3 or greater (> 3.0 x ULN) - Total bilirubin greater than 1.5 x ULN - Direct bilirubin greater than ULN - Serum creatinine level greater than 1.5 times upper limit of normal - Albumin <3.0 g/dl or < 30 g/L

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Pretomanid
200mg tablets
Linezolid
Scored 600mg tablets
Bedaquiline
100mg tablets
Placebo Linezolid
Scored 600 mg tablets

Locations

Country Name City State
Georgia National Center for Tuberculosis and Lung Diseases Tbilisi
Moldova, Republic of Institute of Phthisiopneumology Chiril Draganiuc Chisinau
Russian Federation Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow Moscow
Russian Federation Moscow City Research and Practice Tuberculosis Treatment Centre Moscow
Russian Federation National Medical Research Center of Phthisiopulmonology and Infectious Diseases Moscow
Russian Federation FSBI "Saint-Petersburg Research Institute of Phthisiopulmonology" Saint Petersburg
Russian Federation Ural Research Institute of Phthisiopulmonology Yekaterinburg
South Africa King DinuZulu Hospital Complex Durban
South Africa Clinical HIV Research Unit (CHRU) Sizwe Tropical Diseases Hospital Johannesburg
South Africa Tshepong Hospital Klerksdorp North - West
South Africa Empilweni TB Hospital Port Elizabeth Eastern Cape

Sponsors (1)

Lead Sponsor Collaborator
Global Alliance for TB Drug Development

Countries where clinical trial is conducted

Georgia,  Moldova, Republic of,  Russian Federation,  South Africa, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment Unfavourable status:
Participants not classified as having achieved or maintained culture negative status when last seen
Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture
Participants who had a positive culture not followed by at least two negative cultures when last seen
Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide
Participants definitely or possibly dying from TB related cause during the follow-up phase
Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy
Participants who have had surgery and the resected tissue is cultured and is positive for MTB
Participants lost to follow up or withdrawn from the study before the end of treatment
26 weeks
Secondary Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. Unfavourable status:
Participants not classified as having achieved or maintained culture negative status when last seen
Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture
Participants who had a positive culture not followed by at least two negative cultures when last seen
Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide
Participants definitely or possibly dying from TB related cause during the follow-up phase
Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy
Participants who have had surgery and the resected tissue is cultured and is positive for MTB
Participants lost to follow up or withdrawn from the study before the end of treatment
78 weeks
Secondary Time to Sputum Culture Conversion to Negative Status Through the Treatment Period Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures.
Note:
Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart.
Participants who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit.
26 weeks
Secondary Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures. End of Treatment, 26 weeks
See also
  Status Clinical Trial Phase
Recruiting NCT05738681 - Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial Phase 2/Phase 3
Recruiting NCT05526885 - Tuberculosis Diagnostic Trial of CAD4TB Screening Alone Compared to CAD4TB Screening Combined With a CRP Triage Test, Both Followed by Confirmatory Xpert MTB/RIF Ultra in Communities of Lesotho and South Africa N/A
Completed NCT04369326 - Community Initiated Preventive Therapy for TB N/A
Recruiting NCT04568967 - TB-CAPT EXULTANT - HIV N/A
Completed NCT02337270 - Phase 1 Clinical Trial of the Safety and Immunogenicity of an Adenovirus-based TB Vaccine Administered by Aerosol Phase 1
Not yet recruiting NCT06253715 - Shortened Regimen for Drug-susceptible TB in Children Phase 3
Recruiting NCT04271397 - Immunological Biomarkers in Tuberculosis Management N/A
Withdrawn NCT03639038 - Tuberculosis Diagnosis by Flow Cytometry
Completed NCT03199313 - Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid Phase 1
Recruiting NCT04975178 - Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa Phase 3
Completed NCT04463680 - Rifampin and the Contraceptive Implant Phase 4
Completed NCT03973970 - Assessing the Ability of the T-SPOT®.TB Test (IQ)
Recruiting NCT04230395 - Alcohol Reduction Among People With TB and HIV in India N/A
Completed NCT04874948 - Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment Phase 1
Active, not recruiting NCT02906007 - Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV Phase 1/Phase 2
Not yet recruiting NCT05917210 - Peer-led Implementation of TB-HIV Education and Adherence Counseling in Uganda N/A
Not yet recruiting NCT06017843 - Impact Evaluation of Use of MATCH AI Predictive Modelling for Identification of Hotspots for TB Active Case Finding N/A
Not yet recruiting NCT05845112 - Start Taking Action For TB Diagnosis
Active, not recruiting NCT02715271 - Study of TB Lesions Obtained in Therapeutical Surgery
Completed NCT02781909 - Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis Phase 2