NCT05473195

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 105 (actual)
• Sponsor: TASK Applied Science · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

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 1. BVL-GSK098 9 mg once daily (OD) plus ethionamide 250 mg OD (b9Eto250) 15 2. 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.

Conditions

• Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis (TB)

Interventions

Type	Name	Description
DRUG	BVL-GSK098 9mg	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)
DRUG	Ethionamide 250mg	Ethionamide 250 mg po OD (Eto250)
DRUG	Ethionamide 250 mg	Ethionamide 750 mg po given in a single or divided dose (Eto750)
DRUG	Isoniazid 300 MG	Isoniazid 300 mg po OD (INH)

Timeline

• Start date: 2022-12-06
• Primary completion: 2024-04-16
• Completion: 2024-04-16
• First posted: 2022-07-25
• Last updated: 2025-08-21

Locations

1 site across 1 country: South Africa