Project: Simplified Short Treatment for Tuberculosis

Acronym	Simplici-TB (Reference Number: RIA2017S-2012)
Duration	01/01/2019 - 31/12/2023
Project Topic	Therapy for drug sensitive and resistant tuberculosis (TB) is arduous and expensive – a four drug combination for six months to treat drug sensitive TB; frequently at least five to six drugs plus injections for nine to 30 months for MDR-TB with only a 50% success rate and serious side effects including deafness and blindness. A need exists for novel TB drugs and regimens that are safe, effective, and will shorten the duration of all therapy. Outstanding results have been seen to date in all phases of development with the novel drugs bedaquiline (B) and pretomanid (Pa). Combining these two with the highly active compounds moxifloxacin (M) and pyrazinamide (Z) in a Phase IIb trial has shown superior efficacy compared to results from all previous 2 - month studies. Based on these results and the approval of FDA/EMA to file pretomanid registration, the proposed trial - SimpliciTB, is de-risked, especially so for successful outcomes in MDR-TB. This trial is proposed as an open-label, partially randomized trial to evaluate the efficacy, safety and tolerability of a 4-month treatment of bedaquiline (B), pretomanid (Pa), moxifloxacin (M) and pyrazinamide (Z) compared to a 6-month treatment of HRZE (control) in adult participants with DS-TB and a 6-month treatment of BPaMZ in adults with DR-TB. The dual objective of this proposal is (1) to show the possibility to shorten DS-TB treatment to four months and (2) shorten MDR-TB treatment to six months with the same, all oral, regimen. Parallel work by TB Alliance on EMA and FDA registration in 2019 of pretomanid for XDR-TB through a similar regimen (bedaquiline, pretomanid and linezolid), significantly de-risks this program and providing the potential to utilize a highly efficient, low cost design. This trial is also integrated into an extensive program which will prepare the TB market for rapid global regimen adoption. A successful outcome from this study will provide a short (4 to 6 month), safe, highly effective and easy to administer treatment . The trial (SimpliciTB) will further utilize the capacity of African partners to extend their scientific base and contribute to groundbreaking regimens for TB treatment. This application builds on a collaboration in place for 10 years, supported by EDCTP and other funders. The TB Alliance will act as sponsor and co-funder for SimpliciTB, scientific and clinical input will be provided by the PanACEA African and European partners, subject to the oversight of the PanACEA General Assembly.
Network	EDCTP2
Call	Strategic actions supporting large-scale clinical trials 2017

Project partner

Number	Name	Role	Country
1	The University Court of the University of St Andrews	Coordinator	United Kingdom
3	Centre de Recherches Médicales de Lambaréné	Partner	Gabon
4	Ifakara Health Institute Trust	Partner	Tanzania
6	Instituto Nacional de Saúde	Partner	Mozambique
7	Ludwig-Maximilians-Universitaet Muenchen	Partner	Germany
8	Medical and Molecular Labaratories Limited	Partner	Uganda
12	National Institute for Medical Research - Tanzania	Partner	Tanzania
16	Stichting Katholieke Universiteit- Radboudumc	Partner	Netherlands
17	Swiss Tropical and Public Health Institute	Partner	Switzerland
18	TASK Foundation NPC	Partner	South Africa
21	The Global Alliance for TB Drug Development	Partner	United States
22	The Good Samaritan Foundation, Kilimanjaro Christian Medical Centre	Partner	Tanzania
26	University College London	Partner	United Kingdom
28	University of Cape Town Lung Institute (Pty) Ltd	Partner	South Africa
32	University of Malawi, College of Medicine	Partner	Malawi