Infectious Disease · Clinical trials
Tuberculosis Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About tuberculosis — and why its trials are hard
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains one of the leading infectious killers worldwide, chiefly affecting the lungs but capable of disseminating to almost any organ. Drug-susceptible TB is cured with the decades-old four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) given over six months, and this backbone still underpins global programs. The modern therapeutic frontier is drug-resistant disease. Multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) forms historically required 18-24 months of toxic injectables with poor cure rates. The diarylquinoline bedaquiline (2012) was the first novel TB drug class in 40 years, and pretomanid (2019) enabled the all-oral, six-month BPaL regimen (bedaquiline, pretomanid, linezolid) validated in the Nix-TB trial. These advances have transformed resistant-TB outcomes, cutting treatment from up to two years of injectables down to an oral six-month course. Diagnostics such as rapid molecular assays, latent-infection treatment to prevent reactivation, and vaccine development beyond the century-old BCG remain active priorities as the field pursues shorter, safer, universally effective regimens and works to counter the continued spread of drug resistance.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Isoniazid + rifampin + pyrazinamide + ethambutol (Standard regimen (HRZE)) | 1952-1971 (individual agents) | Drug-susceptible pulmonary TB, 6-month course | British Medical Research Council controlled trials (historical) | Sputum culture conversion and relapse-free cure | Cure rates >95% under directly observed therapy in susceptible disease |
| Bedaquiline (Sirturo) | 2012 | MDR-TB, combination therapy (accelerated approval) | C208 (phase 2b) | Time to sputum culture conversion | Faster culture conversion vs placebo added to background regimen (median ~83 vs 125 days) |
| Pretomanid (Pretomanid (as part of BPaL)) | 2019 | XDR-TB and treatment-intolerant/nonresponsive MDR-TB (with bedaquiline + linezolid) | Nix-TB | Favorable outcome (culture-negative, relapse-free) 6 months post-treatment | ~90% favorable outcome (89/109 patients) with all-oral 6-month regimen |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in tuberculosis development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Moxifloxacin (regimen-shortening) — REMoxTB | Fluoroquinolone-containing 4-month regimens failed to demonstrate non-inferiority to standard 6-month therapy | Higher relapse rates with shortened treatment despite faster early culture conversion |
| Gatifloxacin (regimen-shortening) — OFLOTUB | 4-month gatifloxacin regimen failed non-inferiority for unfavorable outcomes | Increased relapse with shortened duration; safety signals limited fluoroquinolone dose |
Choosing the right endpoint
Primary endpoints that matter in tuberculosis trials
- Sputum culture conversion — Conversion to negative culture is the core microbiologic marker of treatment response and early efficacy
- Favorable outcome (relapse-free cure) — Composite of cure without relapse, typically assessed 6 months after treatment completion
- Time to culture conversion — Continuous early endpoint used in phase 2 to rank new agents' bactericidal activity
- Treatment-emergent resistance — Acquisition of resistance during therapy signals regimen inadequacy
How iNGENū runs tuberculosis trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Tuberculosis clinical trials — FAQs
What is the standard treatment for drug-susceptible TB?
What is the BPaL regimen?
Why did fluoroquinolone regimens fail to shorten treatment?
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