A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Eto Alone and in Combination With BVL-GSK098

NCT05473195 | Completed Phase 2 DMC

• 1 other identifier: TASK-010-BETO
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB)

Outcome Measures

Primary Outcomes (1)

• 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.

  7 days

Secondary Outcomes (1)

• EBA TTP

  7 days

Other Outcomes (1)

• Adverse events

  7 days

Study Arms (7)

Arm 1

EXPERIMENTAL

BVL-GSK098 9 mg once daily (OD) plus ethionamide 250 mg OD (b9Eto250)

Drug: BVL-GSK098 9mg; Drug: Ethionamide 250mg

Arm 2

ACTIVE COMPARATOR

Isoniazid 300 mg po OD (INH)

Drug: Isoniazid 300 MG

Arm 3

EXPERIMENTAL

BVL-GSK098 27 mg OD plus ethionamide 125 mg po OD (b27Eto125)

Drug: BVL-GSK098 9mg; Drug: Ethionamide 250mg

Arm 4

EXPERIMENTAL

BVL-GSK098 27 mg OD plus ethionamide 250 mg po OD (b27Eto250)

Drug: BVL-GSK098 9mg; Drug: Ethionamide 250 mg

Arm 5

EXPERIMENTAL

BVL-GSK098 27 mg OD plus ethionamide 500 mg po OD (b27Eto500)

Drug: Ethionamide 250mg

Arm 6

EXPERIMENTAL

Ethionamide 250 mg po OD (Eto250)

Drug: Ethionamide 250 mg

Arm 7

EXPERIMENTAL

Ethionamide 750 mg po given in a single or divided dose daily (Eto750)

Drug: Ethionamide 250mg

Interventions

BVL-GSK098 9mg DRUG

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)

Also known as: Ethionamide 125 and 250mg

Arm 1; Arm 3; Arm 4

Ethionamide 250mg DRUG

Ethionamide 250 mg po OD (Eto250)

Arm 1; Arm 3; Arm 5; Arm 7

Ethionamide 250 mg DRUG

Ethionamide 750 mg po given in a single or divided dose (Eto750)

Also known as: Ethionamide 250mg

Arm 4; Arm 6

Isoniazid 300 MG DRUG

Isoniazid 300 mg po OD (INH)

Arm 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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).
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• TASK Applied Science: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

TASK Clinical Research Centre

Cape Town, Western Cape, 7530, South Africa

Location

MeSH Terms

Interventions

Ethionamide; Isoniazid

Intervention Hierarchy (Ancestors)

Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Hydrazines; Organic Chemicals

Study Officials

• Reinard McPherson, MBChB

  TASK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single-centre, open-label, clinical trial in two stages. All treatments will be administered orally (PO) on days 1-7.

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: July 25, 2022
• Study Start: December 6, 2022
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately after publication.
• Access Criteria: Not available yet

Locations

ZA (1)