Project: PanACEA, a drug development programme to shorten and simplify treatment of tuberculosis
| Acronym | PanACEA (Reference Number: TRIA2015-1102) |
| Duration | 01/03/2017 - 28/02/2022 |
| Project Topic | PanACEA, a consortium funded previously by EDCTP 1 has managed an extensive drug development portfolio, delivering 6 clinical trials. We propose to continue and expand the programme to accelerate the development of new anti-tuberculosis drug regimens. We take full advantage of innovative trial designs, new microbiological markers of treatment response, pharmacokinetic-pharmacodynamic analyses and novel modelling techniques developed previously. Our objectives are to complete the optimisation of existing drugs and to evaluate two new novel agents. We will go further by testing combinations regimens that will shorten and simplify treatment for both drug-sensitive and drug-resistant tuberculosis. Trials will be conducted at 11 sites throughout sub-Saharan Africa, empowering African scientists in all aspects of an integrated and comprehensive programme for drug development. We will expand our capacity development programme to strengthen African clinical trial sites and research capacity and to strengthen and transfer African scientific leadership. Our key objectives are: 1. To optimise the dose of rifampicin by completion of a maximum tolerated dose study of rifampicin using our established methodology. Groups of 15 patients will each receive 50, 75 and 100 mg/kg, with strict safety stopping rules based on acceptable tolerability and dose-exposure relationships. 2. To assess the safety and efficacy: Q203 which is immediately ready for Phase II clinical evaluation and BTZ043 which will enter the clinical phase later in the programme. We will evaluate these compounds with novel mechanisms of activity through an innovative phase study design, ‘14+14’ phase IIA SMART (Sequential, Multiple Assignment, Randomized Trial). 3. To evaluate several combinations of the optimal doses of rifampicin, Q203, and an optimised dose of pyrazinamide of 40 mg/kg complemented by isoniazid and ethambutol, in a six-arm study using the novel STEP design (the Phase IIC Selection Trial with Extended Post-treatment follow-up). This closes the gap between Phase II and Phase III studies, and by a Bayesian framework analysis of relapse data, will predict the success rate of the new regimens in a future phase III study. An arm containing Q203 together with a novel backbone will be contained, which has the potential to be a universal regimen for drug sensitive and drug resistant TB. This work programme will result in at least two promising regimens with sound prediction data for a successful phase III evaluation, and advance BTZ043 into phase IIB. Our innovative approach will de-risk future investment and accelerate drug development by several years. More information about the project and its progress is available on the PanACEA website. |
| Website | visit project website |
| Network | EDCTP2 |
| Call | Research and Innovation Actions: Improved treatment and clinical management of poverty-related diseases |