A Seamless Phase 2B/C Platform Trial to Evaluate Multiple Regimens and Durations of Treatment in Pulmonary Tuberculosis
The UNITE4TB consortium is a group of universities and pharmaceutical companies funded by the European Union. This consortium are carrying out a trial to find better and faster ways to treat tuberculosis (TB). The standard treatment for TB takes 24 weeks and uses four drugs. The consortium want to find new treatments that are faster but just as safe and effective. In the trial, two new drugs will be used, BTZ-043 and GSK3036656, along with the drugs that are already used to treat TB in a variety of combinations (11 different combinations initially). These new drugs have worked well in tests with animals and have reduced the amount of TB bacteria in people's sputum/phlegm when used alone for two weeks. These new drugs will be used in combination with other TB drugs for a longer time (up to 16 weeks) in people with TB. The UNITE4TB consortium want to see if they work well and are safe. This trial will take place at sites across the world and will involve people with TB of the lungs that would usually respond well to the standard treatment. But the new treatments being tested might also work for people with drug resistant TB, that's harder to treat. The trial has two parts. In the first part, different combinations of drugs will be tried on up to 700 people for 16 weeks. These combinations will be compared to the standard 24-week treatment to see which ones work the best and are safe. In the second part, the best combinations from the first part will be taken to try to find out what the best length of time is to give the treatment for. These combinations will be tried on up to 1800 people giving them either 8, 10, 12, 14 or 16 weeks treatment. The investigators will follow these people for a total of 72 weeks to make sure the treatment is working. The UNITE4TB consortium hope that this trial will find new treatments that are fast, safe, and effective for both regular TB and resistant TB. If it works, it can then be tested again in a bigger trial to be sure.
• Age 18 years or above at screening (or above age of legal consent at screening, if this is higher than 18 years in the jurisdiction in which the study is taking place)
• Clinical evidence of active TB disease, meeting either or both of the following criteria:
‣ Symptoms consistent with pulmonary TB at screening AND/OR
⁃ Imaging findings consistent with active pulmonary TB on chest X-ray performed at screening or within 7 days prior to screening
• At least one sputum specimen produced at screening tested on Xpert MTB/RIF Ultra that has:
‣ a semi-quantitative result of 'medium' or 'high' AND
⁃ does not show rifampicin resistance
• Body weight within the range of 30 to 100kg and body mass index within the range of 15 to 40kg/m2
• Willing to comply with study visits, all study procedures and treatment observation
• Resident at a fixed address that is readily accessible for visiting, within feasible travelling distance to the site and likely to remain resident there for the duration of trial follow-up
• Has provided written informed consent