Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB)Phase 2BETONCT05473195
A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Eto Alone and in Combination With BVL-GSK098
A Phase 2 study testing BVL-GSK098 9mg, Ethionamide 250mg and Ethionamide 250 mg in people with Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB), run by TASK Applied Science at 1 site in South Africa.
Trial summary
To evaluate the 7-day early bactericidal activity (EBA), pharmacokinetics (PK), safety and tolerability of ethionamide (Eto) with or without BVL-GSK098 in participants with rifampicin- and isoniazid-susceptible pulmonary TB. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB)
- What is being tested?
- BVL-GSK098 9mg, Ethionamide 250mg and Ethionamide 250 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteSouth Africa
- Study dates
- 6 Dec 2022to 16 Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants are required to meet all the following criteria in order to be randomized.
- Provide written, informed consent prior to all trial-related procedures.
- Male or female, aged between 18 and 65 years, inclusive.
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Newly diagnosed and untreated pulmonary TB.
- Rifampicin- and isoniazid-susceptible pulmonary TB as determined by molecular testing (GeneXpert XDR or Genotype MTBDRplus for INH).
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- A chest X-ray taken during the screening period or up to 2 weeks before screening which, in the opinion of the investigator, is consistent with TB.
- GeneXpert positive with a quantitative readout of medium or high.
- Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).
- Be of non-childbearing potential or using effective methods of birth control.
- For WOCBP, injectable or other contraceptive methods (per Appendix 1) need to be given prior to or during screening, and at least 2 days prior to first dose of IP.
Who cannot join
- Participants will be excluded from participation if they fulfil any of the following criteria.
- Medical History
- Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
- History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator
- History of hypothyroidism
- QTcF of >450 ms at baseline
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- Clinically significant evidence of extrathoracic TB, as judged by the investigator.
- History of allergy to any of the trial IP as confirmed by the clinical judgement of the investigator.
- Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.
- HIV positive AND:
- CD4 < 250cells/mm3
- OR, on ART in stage 1 only. Participants established on ART (2 NRTIs and dolutegravir) for more than 30 days at start of screening are eligible for participation in stage 2.
- NOTE: ART permitted in Stage 2 is limited to the following in line with local guidelines for 1st line ART:
- NRTIs selected from: Emtricitabine, Lamivudine, Tenofovir
- PLUS Dolutegravir
- As the drug-drug interaction potential of ART has not been fully investigated with the IP, NNRTIs (efavirenz, nevirapine) and other protease inhibitors will not be permitted in this study.
- Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of trial participation. Male participant planning to conceive a child for at least 90 days, after the last dose of study intervention in the trial.
- Treatment History
- Participation in other clinical studies with investigational agents within 8 weeks prior to screening.
- Treatment received for this episode of TB with any drug active against M.tb (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides).
- Treatment with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
TASK Clinical Research Centre
Cape Town, Western Cape, 7530
About this study
Official title: A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Ethionamide Alone and in Combination With BVL-GSK098 Administered Orally to Adults With Newly Diagnosed, Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis
To evaluate the 7-day early bactericidal activity (EBA), pharmacokinetics (PK), safety and tolerability of ethionamide (Eto) with or without BVL-GSK098 in participants with rifampicin- and isoniazid-susceptible pulmonary TB.
Read the detailed description
A single-centre, open-label, clinical trial in two stages. All treatments will be administered orally (PO) on days 1-7.
Stage 1 will recruit 15 participants into arm 1 who will receive Eto and a low dose BVL-GSK098 combination (bEto), including 3 participants from the control arm (arm 2). Participants will be randomized 5:1. This will be followed by a recruitment pause and an interim analysis to evaluate safety of the combination.
Stage 1:
Arm Regimen Participants
- BVL-GSK098 9 mg once daily (OD) plus ethionamide 250 mg OD (b9Eto250) 15
- Isoniazid 300 mg po OD (INH) 3 * BVL-GSK098 9 mg will be given 12-hourly on Day one (loading dose), then once daily on Day 2-7.
An interim safety analysis will be performed after all Stage 1 participants complete the end of treatment visit (Day 8). If the b9Eto250 arm meets the predefined safety criteria (Section 9), the study will proceed to Stage 2. Recruitment will then continue with the remaining arms randomized in a 4:5:5:5:5:5 ratio.
Stage 2:
Arm Regimen Participants 2 Isoniazid 300 mg po OD (INH) 12 3 BVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125) 15 4 BVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250) 15 5 BVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500) 15 6 Ethionamide 250 mg po OD (Eto250) 15 7 Ethionamide 750 mg po given in a single or divided dose daily (Eto750) 15
- BVL-GSK098 27 mg will be given 12-hourly on Day one (loading dose), then once daily on Day 2-7. Ethionamide 750 mg given in divided doses Day 1-3, and OD Day 4-7.
Participants on INH will serve as control for the EBA quantitative mycobacteriology. The study will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.
- Being tested
- BVL-GSK098 9mg, Ethionamide 250mg, Ethionamide 250 mg, Isoniazid 300 MG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BVL-GSK098 9mgDrug
Also called Ethionamide 125 and 250mg
BVL-GSK098 9 mg once daily po OD plus ethionamide 250 mg po OD (b9Eto250) BVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125 BVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250) BVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500)
Ethionamide 250mgDrug
Ethionamide 250 mg po OD (Eto250)
Ethionamide 250 mgDrug
Also called Ethionamide 250mg
Ethionamide 750 mg po given in a single or divided dose (Eto750)
Isoniazid 300 MGDrug
Isoniazid 300 mg po OD (INH)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | BVL-GSK098 9 mg once daily (OD) plus ethionamide 250 mg OD (b9Eto250) Receives: Drug: BVL-GSK098 9mg; Drug: Ethionamide 250mg |
| Arm 2 | Active comparator | Isoniazid 300 mg po OD (INH) Receives: Drug: Isoniazid 300 MG |
| Arm 3 | Experimental | BVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125) Receives: Drug: BVL-GSK098 9mg; Drug: Ethionamide 250mg |
| Arm 4 | Experimental | BVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250) Receives: Drug: BVL-GSK098 9mg; Drug: Ethionamide 250 mg |
| Arm 5 | Experimental | BVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500) Receives: Drug: Ethionamide 250mg |
| Arm 6 | Experimental | Ethionamide 250 mg po OD (Eto250) Receives: Drug: Ethionamide 250 mg |
| Arm 7 | Experimental | Ethionamide 750 mg po given in a single or divided dose daily (Eto750) Receives: Drug: Ethionamide 250mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
EBA CFU
The EBA CFU(0-7) as determined by the predicted rate of change in log10CFU per ml sputum over the period day 0 to day 7 will be described using linear, bi-linear or non-linear functions using nonlinear mixed effects modelling as dictated by the data of log10CFU over time and relation to drug exposure.
Predicted estimate of rates of change including uncertainties for the potential differences in treatment effects between the groups will be given and graphically illustrated.
Measured: 7 days
Secondary outcomes (1)
EBA TTP
The EBA TTP(0-7) as determined by the predicted rate of change in TTP over the period day 0 to day 7 will be described using linear, bi-linear or non-linear functions using nonlinear mixed effects modelling of TTP over time and relation to drug exposure.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2022
- Study start6 Dec 2022
- Primary completion16 Apr 2024
- Study completion16 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A single-centre, open-label, clinical trial in two stages. All treatments will be administered orally (PO) on days 1-7.
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- TASK Applied Science
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Reinard McPherson, MBChB, Principal investigator, TASK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05473195
- Sponsor's protocol ID
- TASK-010-BETO
- Acronym
- BETO
- Status last verified
- Aug 2025
- First submitted
- 12 Jul 2022
- Last updated
- 21 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plan not yet available
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Ethionamide Alone and in Combination With BVL-GSK098 Administered Orally to Adults With Newly Diagnosed, Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT05473195
- Acronym / sponsor ID
- BETO / TASK-010-BETO
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- TASK Applied ScienceUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 6 Dec 2022 (actual)
- Primary completion
- 16 Apr 2024 (actual)
- Study completion
- 16 Apr 2024 (actual)
- First posted
- 25 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the 7-day early bactericidal activity (EBA), pharmacokinetics (PK), safety and tolerability of ethionamide (Eto) with or without BVL-GSK098 in participants with rifampicin- and isoniazid-susceptible pulmonary TB.
Detailed description
A single-centre, open-label, clinical trial in two stages. All treatments will be administered orally (PO) on days 1-7.
Stage 1 will recruit 15 participants into arm 1 who will receive Eto and a low dose BVL-GSK098 combination (bEto), including 3 participants from the control arm (arm 2). Participants will be randomized 5:1. This will be followed by a recruitment pause and an interim analysis to evaluate safety of the combination.
Stage 1:
Arm Regimen Participants
- BVL-GSK098 9 mg once daily (OD) plus ethionamide 250 mg OD (b9Eto250) 15
- Isoniazid 300 mg po OD (INH) 3 * BVL-GSK098 9 mg will be given 12-hourly on Day one (loading dose), then once daily on Day 2-7.
An interim safety analysis will be performed after all Stage 1 participants complete the end of treatment visit (Day 8). If the b9Eto250 arm meets the predefined safety criteria (Section 9), the study will proceed to Stage 2. Recruitment will then continue with the remaining arms randomized in a 4:5:5:5:5:5 ratio.
Stage 2:
Arm Regimen Participants 2 Isoniazid 300 mg po OD (INH) 12 3 BVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125) 15 4 BVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250) 15 5 BVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500) 15 6 Ethionamide 250 mg po OD (Eto250) 15 7 Ethionamide 750 mg po given in a single or divided dose daily (Eto750) 15
- BVL-GSK098 27 mg will be given 12-hourly on Day one (loading dose), then once daily on Day 2-7. Ethionamide 750 mg given in divided doses Day 1-3, and OD Day 4-7.
Participants on INH will serve as control for the EBA quantitative mycobacteriology. The study will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- A single-centre, open-label, clinical trial in two stages. All treatments will be administered orally (PO) on days 1-7.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: BVL-GSK098 9mg, Drug: Ethionamide 250mgBVL-GSK098 9 mg once daily (OD) plus ethionamide 250 mg OD (b9Eto250) |
| Arm 2 | Active comparator | Drug: Isoniazid 300 MGIsoniazid 300 mg po OD (INH) |
| Arm 3 | Experimental | Drug: BVL-GSK098 9mg, Drug: Ethionamide 250mgBVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125) |
| Arm 4 | Experimental | Drug: BVL-GSK098 9mg, Drug: Ethionamide 250 mgBVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250) |
| Arm 5 | Experimental | Drug: Ethionamide 250mgBVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500) |
| Arm 6 | Experimental | Drug: Ethionamide 250 mgEthionamide 250 mg po OD (Eto250) |
| Arm 7 | Experimental | Drug: Ethionamide 250mgEthionamide 750 mg po given in a single or divided dose daily (Eto750) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participants are required to meet all the following criteria in order to be randomized.
- Provide written, informed consent prior to all trial-related procedures.
- Male or female, aged between 18 and 65 years, inclusive.
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Newly diagnosed and untreated pulmonary TB.
Key exclusion criteria (21 listed)
- Medical History
- Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
- History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator
- History of hypothyroidism
- QTcF of >450 ms at baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BVL-GSK098 9mgAlso: Ethionamide 125 and 250mgBVL-GSK098 9 mg once daily po OD plus ethionamide 250 mg po OD (b9Eto250) BVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125 BVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250) BVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500) | Drug | Arm 1, Arm 3, Arm 4 |
| Ethionamide 250mgEthionamide 250 mg po OD (Eto250) | Drug | Arm 1, Arm 3, Arm 5, Arm 7 |
| Ethionamide 250 mgAlso: Ethionamide 250mgEthionamide 750 mg po given in a single or divided dose (Eto750) | Drug | Arm 4, Arm 6 |
| Isoniazid 300 MGIsoniazid 300 mg po OD (INH) | Drug | Arm 2 |
Primary outcome
EBA CFU
Time frame: 7 days
The EBA CFU(0-7) as determined by the predicted rate of change in log10CFU per ml sputum over the period day 0 to day 7 will be described using linear, bi-linear or non-linear functions using nonlinear mixed effects modelling as dictated by the data of log10CFU over time and relation to drug exposure. Predicted estimate of rates of change including uncertainties for the potential differences in treatment effects between the groups will be given and graphically illustrated.
1 secondary outcome
EBA TTP
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2025.
- Individual participant dataSharing planned: Yes. Plan not yet available
Related trials for Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB)
Not yet recruitingPhase 3
A Short Regimen for Rifampicin-resistant Isoniazid-susceptible TB
Tuberculosis, Pulmonary
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reinard McPherson, MBChB principal investigator
TASK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BVL-GSK098 9mg, Ethionamide 250mg and Ethionamide 250 mg in people with Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB), run by TASK Applied Science at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EBA CFU (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2025.