Trial will explore shorter regimen for TB treatment
TB Alliance announced it has begun a clinical trial to test the effectiveness of a new, shorter four-drug regimen for treating most types of tuberculosis, including multidrug-resistant infections.
The first patients have been enrolled in the SimpliciTB trial in Tbilisi, Georgia, according to a news release. TB Alliance said it expects to enroll 450 patients at 26 centers in 10 countries in Africa, Asia, Europe and Latin America.
“This study will aim to show that it is effective to fully treat and eradicate TB in [most] patients with this regimen,” Daniel E. Everitt, MD, vice president and senior medical officer at TB Alliance told Infectious Disease News. “The key outcome is a durable cure for a relapse-free survival.”
Researchers will randomly assign 300 patients with drug-sensitive TB to receive either an oral regimen of bedaquiline, pretomanid, moxifloxacin and pyrazinamide (BPaMZ) for 4 months (n = 150) or the standard regimen of isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) for 6 months (n = 150). An additional 150 patients with multidrug-resistant TB (MDR-TB) will receive the BPaMZ regimen for 6 months, instead of a standard treatment regimen that can last 9 to 20 months and includes injections.
TB Alliance noted in the release that people with MDR-TB are often untreated and only half of those who do receive treatment are cured.
All patients will be evaluated 24 months after the beginning of treatment.
If the trial is successful, it will show that more than 99% of patients with TB can be treated by the new regimen, Everitt told Infectious Disease News. He said the regimen fits with new WHO guidelines for MDR-TB, which prioritize oral treatment over injections.
“WHO is encouraging the use of newer drugs like bedaquiline,” he said. “The regimen will be an improvement over the recommendation they are making now. It will be all oral and will also be a much shorter treatment duration than what is currently available.”
Pretomanid is an investigational drug that will be reviewed in the near future, so the study is helping to test it in the TB population, Everitt said.
The BPaMZ regimen was previously studied in a phase 2B study called NC-005. The study found that patients with MDR-TB who were treated with the BPaMZ regimen cleared TB bacteria from their lungs up to three times faster than drug-sensitive TB patients treated with standard HRZE treatment, according to the release. NC-005 was an 8-week trial conducted in Uganda, South Africa and Tanzania.
Building on those results, researchers in the SimpliciTB trial will test BPaMZ for a longer duration against both drug-sensitive TB and MDR-TB.
“Hopefully, we will have one standard regimen that can be used to treat more than 99% of all patients with TB for a shorter period of time than they can currently be treated,” Everitt said. “This is an all-oral, once-a-day regimen that does not include any injection. And, in the course of the study, we hope to show that it is well-tolerated, safe and better than current drugs being used.” – by Bruce Thiel
Disclosure: Everitt reports holding stock in Johnson & Johnson, which codeveloped bedaquiline.