Pulmonary Tuberculosis Clinical Trial
Official title:
A Phase 2, Partially-blinded, Randomised Trial Assessing the Safety and Efficacy of TBAJ-876 or Bedaquiline, in Combination With Pretomanid and Linezolid in Adult Participants With Newly Diagnosed, Drug-sensitive, Smear-positive Pulmonary Tuberculosis
NCT number | NCT06058299 |
Other study ID # | NC-009 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | October 24, 2023 |
Est. completion date | June 2026 |
The goal of this clinical trial is to evaluate 3 dose levels of TBAJ876 for 8 weeks in combination with pretomanid and linezolid, compared to 8 weeks of Isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE), in adult participants with newly diagnosed, smear-positive, pulmonary drug sensitive tuberculosis (DS-TB). The main questions the trial aims to answer are: - What is the optimal dose of TBAJ876 to continue further in development. - What is the bactericidal activity of bedaquiline with pretomanid and linezolid (B-Pa-L) compared to 2HRZE and TBAJ876-Pa-L over 8 weeks - What is the efficacy and safety of the 26-week B-Pa-L regimen compared with the SOC (2HRZE/4HR) in participants with DS-TB. Participants will be seen regularly during treatment (up to 26 weeks) and follow-up (52 weeks post treatment) for safety and efficacy assessments, including but not limited to: - Safety labs, ECGs, vital signs, physical exams, PK sampling, neuropathy assessments and adverse event monitoring - Sputum collection
Status | Recruiting |
Enrollment | 300 |
Est. completion date | June 2026 |
Est. primary completion date | February 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - Signed informed consent - DS-TB as defined as sensitive to rifampicin and isoniazid by rapid sputum-based test AND either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB - Of non-childbearing potential OR using effective birth control methods - Body weight = 35 kg Exclusion Criteria: - Karnofsky score < 60 at screening - Any evidence of extrapulmonary TB - Cardiovascular or QT prolongation risk factors - Pregnant or breast-feeding Any of the following lab toxicities: - Platelets <100,000/mm³ - Creatinine >1.3 x ULN - Haemoglobin <9.5 g/dL or <95 g/L - Absolute neutrophil count <800/mm³ - Serum potassium less than the lower limit of normal for the laboratory. - ALT and/or AST =2.5 x ULN - Total bilirubin =1.6 x ULN - Direct bilirubin >1 x ULN - Haemoglobin A1c =8.0% - Total lipase =1.5 x ULN - Total amylase =1.5 x ULN - CPK >3 x ULN (if >3 x ULN, enquire about the participant's recent strenuous activity and consider repeating the test within the screening window) - TSH >1 x ULN - Positive results at screening for HBsAg, HAV IgM, or hepatitis C antibodies For participants living with HIV only: - CD4+ count<200 cells/µL. - WHO Clinical Stage 4 HIV disease - Participant does not agree to use DTG/TFV/3TC during trial if ARV therapy is indicated, and randomised to the TBAJ876 or the B-Pa-L regimen - If initiation of ARV therapy is indicate, participants who are known to be intolerant, non-responsive to DTG/TFV/3TC or have DTG/TFV/3TC as a contraindication. |
Country | Name | City | State |
---|---|---|---|
Georgia | National Center for Tuberculosis and Lung Diseases | Tbilisi | |
Philippines | De La Salle Medical and Health Sciences Institute | Dasmariñas | |
Philippines | Tropical Disease Foundation | Makati City | |
Philippines | Lung Center of the Philippines | Quezon City | |
South Africa | Madibeng Centre for Research | Brits | |
South Africa | Desmond Tutu Health Foundation | Cape Town | |
South Africa | TASK Brooklyn | Cape Town | |
South Africa | University of Cape Town Lung Institute (UCTLI) | Cape Town | |
South Africa | Setshaba Research Centre | City Of Tshwane | |
South Africa | Enhancing Care Foundation | Durban | |
South Africa | Synergy Biomed Research Institute (SBRI) | East London | |
South Africa | TB and HIV Investigative Network (THINK) | Hillcrest | |
South Africa | WITS, Clinical HIV Research Unit (CHRU) Themba Lethu Clinic, Helen Joseph Hospital | Johannesburg | |
South Africa | Perinatal HIV Research Unit (PHRU) | Klerksdorp | |
South Africa | Isango Lethemba TB Research Unit | Port Elizabeth | |
South Africa | The Aurum Institute | Rustenburg | |
Tanzania | NIMR-MBEYA Medical Research Center | Mbeya | |
Tanzania | Kilimanjaro Christian Medical Centre | Moshi | |
Tanzania | National Institute for Medical Research (NIMR) | Mwanza | |
Uganda | Case Western Reserve University- Research collaboration Uganda | Kampala | |
Uganda | Joint Clinical Research Centre (JCRC) | Kampala |
Lead Sponsor | Collaborator |
---|---|
Global Alliance for TB Drug Development |
Georgia, Philippines, South Africa, Tanzania, Uganda,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Time to stable sputum conversion | Time to stable sputum culture conversion to negative status using data from weekly cultures through 8 weeks of treatment. | Through 8 weeks of treatment | |
Secondary | Favorable Outcome 26 Weeks after End of Treatment | Proportion of participants with a favourable outcome at 26 weeks after the end of treatment. | 26 weeks after end of treatment |
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