Nicotinamide with bedaquiline, pretomanid, and linezolid for drug‑susceptible lung tuberculosis
A Phase 2, Open-label, Randomized Controlled Trial to Assess the Safety, Bactericidal Activity, and Pharmacokinetics of Nicotinamide in Combination With Bedaquiline, Pretomanid, and Linezolid in Adults With Drug-susceptible Pulmonary Tuberculosis
This test will see if adding nicotinamide to bedaquiline, pretomanid, and linezolid is safe and helps treat adults with drug‑susceptible pulmonary TB.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 165 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Gates Medical Research Institute Academic / other |
| Locations | 4 sites (Johannesburg, Gauteng and 3 other locations) |
| Trial ID | NCT07517445 on ClinicalTrials.gov |
What this trial studies
This Phase 2 interventional trial gives adults with drug‑susceptible pulmonary TB a regimen that includes bedaquiline, pretomanid, and linezolid and examines the effect of adding nicotinamide on bactericidal activity and safety. Participants are followed during treatment with regular sputum sampling to measure bacterial load and with clinical and laboratory monitoring for adverse events. Enrollment is limited to adults 18–65 with newly diagnosed, rifampicin‑ and isoniazid‑sensitive pulmonary TB who can produce sputum and meet weight and contraception requirements. The study is conducted at multiple clinical research sites in South Africa.
Who should consider this trial
Good fit: Adults aged 18–65 with newly diagnosed, rifampicin‑ and isoniazid‑sensitive pulmonary tuberculosis who can produce sputum and meet the study's weight and contraception requirements.
Not a fit: People with drug‑resistant TB, recent or recurrent TB within exclusion windows, extrapulmonary‑only disease, pregnant or breastfeeding women, or those with uncontrolled HIV or other disqualifying comorbidities are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, adding nicotinamide could speed bacterial clearance and improve treatment outcomes for people with drug‑susceptible pulmonary TB.
How similar studies have performed: Bedaquiline, pretomanid, and linezolid have shown efficacy in other TB regimens (notably for drug‑resistant TB), but combining nicotinamide with this regimen for drug‑susceptible TB is a relatively novel approach without established large‑scale proof of benefit.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age 18-65 years at consent * Body weight 40-100 kg at screening * Written informed consent obtained * Newly diagnosed pulmonary TB, rifampicin- and isoniazid-sensitive * ≥1+ AFB smear OR positive Xpert semi-quantitative result * Molecular confirmation of M. tuberculosis * Chest X-ray consistent with TB (Investigator assessment) * Able to spontaneously produce sputum * Contraception requirements met * Females Of Child Bearing Potential: 2 approved contraceptive methods or abstinence * Males: contraception or abstinence through 90 days post-dose Exclusion Criteria: * Prior TB within 3 years, \>1 prior episode, or anti-TB treatment within 60 days * Extrapulmonary TB (except non-significant pleural/lymph node disease) * Clinically significant comorbidities or substance abuse impacting safety/compliance * Pregnant or breastfeeding * HIV-positive AND any of the following: * Not on ART or on ART \<3 months * CD4 \<200 cells/µL * Viral load \>200 copies/mL * AIDS-defining illness (other than pulmonary TB) * Screening lab abnormalities (protocol-defined LFTs, hematology, hepatitis B or C, HbA1c) * Clinically significant ECG abnormality * Use of prohibited concomitant medications (e.g., strong CYP3A4 modifiers, certain SSRIs)
Where this trial is running
Johannesburg, Gauteng and 3 other locations
- Wits RHI - Shandukani Research — Johannesburg, Gauteng, South Africa (Not_yet_recruiting)
- The Aurum Institute Clinical Research Site - Pretoria — Pretoria, Gauteng, South Africa (Not_yet_recruiting)
- TASK Clinical Research Centre — Cape Town, Western Cape, South Africa (Recruiting)
- Centre of Tuberculosis Research Innovation — Cape Town, Western Cape, South Africa (Not_yet_recruiting)
Study contacts
- Study coordinator: Gates MRI
- Email: Clinical.trials@gatesmri.org
- Phone: +857-702-2108
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.