Four-month delamanid, bedaquiline and quabodepistat for drug-susceptible TB: proof of concept

Design

Phase 2b/c, open-label, randomised, non-inferiority proof-of-concept

Population

122 adults with newly diagnosed drug-susceptible pulmonary TB, South Africa

Primary outcome

Sputum culture conversion by end of treatment

Effect

96.0% (4-month pooled) vs 100% (6-month standard); difference −4.0% (80% CI −7.4 to 3.4)

This open-label phase 2b/c trial at six South African sites, published on 29 May 2026, randomised 122 adults with newly diagnosed drug-susceptible pulmonary TB to four months of delamanid, bedaquiline and one of three doses of quabodepistat, a new DprE1 inhibitor, or six months of standard rifampicin, isoniazid, ethambutol and pyrazinamide.

At the end of treatment, sputum culture conversion was 96.0% in the pooled four-month groups against 100% on standard therapy (difference −4.0%, 80% CI −7.4 to 3.4), meeting a 12% non-inferiority margin. Grade 3 or worse adverse events were 11–20% across the new-regimen arms against 5% on standard therapy, with no serious adverse events attributed to the drugs.

The regimen is rifampicin-free, which matters for drug interactions, but it uses bedaquiline and delamanid, the backbone of drug-resistant TB treatment. Spending them on drug-susceptible disease raises resistance-stewardship questions. End-of-treatment conversion is not cure: relapse is the outcome that decides shortened TB regimens, and it is not reported here. Standard therapy, and India's national TB programme regimens, remain unchanged.

• Continue standard six-month therapy for drug-susceptible TB; this regimen is investigational.
• Culture conversion at the end of treatment is not cure; relapse data are still awaited.
• The regimen uses bedaquiline and delamanid, drugs reserved for drug-resistant TB in current programmes.
• A rifampicin-free option would matter for patients on interacting drugs such as some antiretrovirals.

Why it matters

Shorter, interaction-light TB treatment would ease adherence, but it must not spend the drugs that protect against resistance.

Don't overread it

This is a small proof-of-concept trial with an 80% confidence interval and no relapse data; it does not show the regimen cures TB as well as standard therapy.

The statistics, in plain English

The trial used an 80% confidence interval, which is narrower and less demanding than the usual 95%. With only 21 people on standard therapy, small differences cannot be ruled out.

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