Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202311505748497 Date of Approval: 10/11/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Phase 2, partially-blinded, randomised trial assessing the safety and efficacy of TBAJ876 or bedaquiline, in combination with pretomanid and linezolid in adult participants with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis
Official scientific title A phase 2, partially-blinded, randomised trial assessing the safety and efficacy of TBAJ876 or bedaquiline, in combination with pretomanid and linezolid in adult participants with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis
Brief summary describing the background and objectives of the trial This is a phase 2, dose-ranging trial of TBAJ876 in participants with DS-TB. The bactericidal activity and safety of 3 doses of TBAJ876 (25 mg, 50 mg, and 100 mg) in combination with pretomanid 200 mg and linezolid 600 mg will be compared to the SOC (2HRZE) after 8 weeks of treatment to determine the optimal dose of TBAJ876 to carry forward in subsequent phases of development. The trial will also examine the bactericidal activity of B-Pa-L compared to 2HRZE and TBAJ876-Pa-L over 8 weeks and examine the efficacy and safety of the 26-week B-Pa-L regimen compared with the SOC (2HRZE/4HR) in participants with DS-TB. The trial will also evaluate the efficacy, in terms of relapse rate at follow-up Week 26 and Week 52 compared to the SOC arm, of 8 weeks of 25 mg, 50 mg, and 100 mg of TBAJ876-Pa-L arms (maximal total treatment duration of 26 weeks). These data will supplement the TBAJ876 dose ranging findings at Week 8 and provide insight into the optimal duration of treatment required for the TBAJ876-Pa-L regimens. All these data will support the planning for a future phase 3 trial. Trial Objectives: The objectives of the trial are to evaluate the efficacy, safety, and tolerability of TBAJ876 (3 doses) or bedaquiline in combination with pretomanid and linezolid in adult participants with newly diagnosed, smear-positive pulmonary DS-TB in comparison to the SOC.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 15/09/2023
Actual trial start date
Anticipated date of last follow up 22/02/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 300
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NC009 Sponsor-issued protocol number
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group TBAJ876 25 mg Pa L HR Up to 5 tablets orally once daily 8 -18 weeks TBAJ876 25 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR (isoniazid, rifampicin) for 7 to 18 weeks 60
Experimental Group TBAJ876 50mg Pa L HR Up to 5 tablets orally once daily 8 -18 weeks TBAJ876 50 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR (isoniazid, rifampicin) for 7 to 18 weeks 60
Experimental Group TBAJ876 100mg Pa L HR Up to 5 tablets orally once daily 8 -18 weeks TBAJ876 100 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR (isoniazid, rifampicin) for 7 to 18 weeks 60
Experimental Group B Pa L 4 - 9 tablets orally once daily 8 -16 weeks Bedaquiline 200 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by bedaquiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 18 weeks 60
Control Group HRZE Up to 5 tablets orally once daily 8 -18 weeks Isoniazid (H) + rifampicin (R) + pyrazinamide (Z), ethambutol (E) for 8 weeks followed by HR (isoniazid, rifampicin) for 18 weeks 60 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Signed written informed consent prior to undertaking any trial-related procedures. 2. Participants aged 18 to 65 years, inclusive. 3. Body weight (in light clothing and no shoes) ≥35 kg. 4. Sputum positive for tubercle bacilli (at least 1+ on the IUATLD/WHO scale [Section 13.4] on smear microscopy) at the trial laboratory. 5. DS-TB participants defined as the following: a. Sensitive to rifampicin and isoniazid by rapid sputum-based test AND b. 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. 6. A chest x-ray during the screening period or within 14 days of screening which in the opinion of the investigator is compatible with pulmonary TB. 7. Be of non-childbearing potential OR using effective methods of birth control 1. History or presence of pulmonary, hepatic, musculoskeletal abnormalities, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, psychiatric disease 2. Cardiovascular abnormalities 3. Karnofsky performance status score of <60%. 4. Abuse of alcohol or illegal drugs 5. Historical and/or current use of local traditional medications/herbs (such as St. John’s wort) 6. Being, or about to be, treated for malaria. 7. Is critically ill and, in the judgment of the investigator, has a diagnosis likely to result in death during the trial or the follow-up period. 8. Any evidence of extrapulmonary TB. Pleural effusion occupying <50% of hemithorax or concomitant intra- or extra-thoracic lymphadenopathy are not exclusions. 9. For participants living with HIV (as specified by protocol). 10. Having participated in other clinical trials with investigational agents within 8 weeks prior to Day 1 or currently randomised in an investigational drug trial. 11. Participants with QTcF interval on ECG >450 msec at screening visit. 12. Participants with any of the following at the screening visit per medical history: a. A personal or family history of congenital QT prolongation, b. A history of known, untreated, and uncontrolled hypothyroidism, c. A history of or ongoing bradyarrhythmia, d. A history of Torsade de Pointe. 13. Unstable Diabetes Mellitus which required hospitalization for hyper- or hypo-glycemia within the past year prior to the start of screening. 14. Females who have a positive pregnancy test during the screening visit or are already known to be pregnant, breastfeeding, or planning to conceive a child during the trial or within 6 months of completing treatment with IMP. Males planning to conceive a child during the trial or within 6 months of stopping treatment with IMP. 15. Any diseases or conditions in which the use of standard TB drugs or any of their components is contra-indicated, including but not limited to drug allergy. 16. Use of any drug within 30 days prior to randomisation known to prolong QTc interval. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 26/05/2023 National Institute of Medical Research
Ethics Committee Address
Street address City Postal code Country
11101 Dar es Salaam Dodoma 40478 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 20/03/2023 Mbeya Medica Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P O Box 419 Mbeya 2410 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/06/2023 College Research Ethic Review Committee
Ethics Committee Address
Street address City Postal code Country
P.O.Box 2240 Moshi 2240 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/05/2023 Joint Clinical Research Centre
Ethics Committee Address
Street address City Postal code Country
Plot 101 Lubowa, off Entebbe Road Kampala N/A Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/08/2023 Uganda National Council for Science and Technology
Ethics Committee Address
Street address City Postal code Country
Plot 6 Kimera Road, Ntinda Kampala N/A Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to stable sputum culture conversion to negative status using data from weekly cultures through 8 weeks of treatment. 8 weeks
Secondary Outcome Proportion of participants with a favourable outcome at 26 weeks after the end of treatment. 26 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Uganda Case Western Reserve University Research Collaboration Upper Hill Road, Mulago Hospital Complex Kampala Uganda
Joint Clinical Research Centre Plot 101 Lubowa Estates, Off Entebbe Road Kampala Uganda
National Institute for Medical Research Mbeya Medical Research Centre Hospital Hill Road Mbeya Tanzania
Kilimanjaro Clinical Research Institute Kilimanjaro Christian Medical Centre Sokoine Road Moshi Tanzania
National Institute for Medical Research Mwanza Medical Research Centre Isamilo area Nyamagana Mwanza Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
TB Alliance 80 Pine Street, 20th Floor New York 10005 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor TB Alliance 80 Pine Street, 20th Floor New York 10005 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Harriet Mayanja Kizza harriet.mayanja@mak.ac.ug +256772593482 Uganda Case Western Reserve University Research Collaboration, Upper Hill Road Mulago Hospital Complex
City Postal code Country Position/Affiliation
Kampala Uganda National PI Uganda
Role Name Email Phone Street address
Public Enquiries Harriet Mayanja Kizza harriet.mayanja@mak.ac.ug +256772593482 Uganda Case Western Reserve University Research Collaboration, Upper Hill Road Mulago Hospital Complex
City Postal code Country Position/Affiliation
Kampala Uganda National PI Uganda
Role Name Email Phone Street address
Scientific Enquiries Harriet Mayanja Kizza harriet.mayanja@mak.ac.ug +256772593482 Uganda Case Western Reserve University Research Collaboration, Upper Hill Road Mulago Hospital Complex
City Postal code Country Position/Affiliation
Kampala Uganda National PI Uganda
Role Name Email Phone Street address
Principal Investigator Nyanda Elias Ntinginya nelias@mmrp.org +255252503364 Hospital Hill Road
City Postal code Country Position/Affiliation
Mbeya Tanzania National PI Tanzania
Role Name Email Phone Street address
Public Enquiries Nyanda Elias Ntinginya nelias@mmrp.org +255252503364 Hospital Hill Road
City Postal code Country Position/Affiliation
Mbeya Tanzania National PI Tanzania
Role Name Email Phone Street address
Scientific Enquiries Nyanda Elias Ntinginya nelias@mmrp.org +255252503364 Hospital Hill Road
City Postal code Country Position/Affiliation
Mbeya Tanzania National PI Tanzania
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes There is currently no plan to implement Individual Patient Sharing of data. However, de-identified participant data will be available but accessed upon request and approval by TB Alliance/sponsor. In additional, third parties may obtain study access upon request and permission of TB Alliance/sponsor. Clinical Study Report 12 months after the final database lock. Controlled access
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information