The PanACEA SUDOCU study completed its recruitment: a total of 75 participants were randomized to 5 arms (15 participants each) with a wide range of sutezolid doses (from 0mg to 800mg BID given over three months).
With this open-label, randomized, phase 2B, dose selection study (ClinicalTrials.gov identifier NCT03959566) we aim to describe the safety/tolerability-exposure relationship of sutezolid (and its main metabolite), in combination with standard-dose bedaquiline, delamanid and moxifloxacin.
Participating PanACEA sites were The Aurum Institute for Health Research (Johannesburg, South Africa), Kilimanjaro Clinical Research Institute (Moshi, Arusha, Tanzania), Ifakara Health Institute (Bagamoyo, Tanzania), and National Institute for Medical Research (NIMR – MMRC) (Mbeya, Tanzania).
The current TB drug development pipeline contains only a limited number of novel agents ready for advanced phase 2 testing, and sutezolid (an oxazolidinone) is one of these compounds in the clinical development stage. Sutezolid will most likely have similar or better efficacy as its sister compound linezolid, however is probably much less toxic as indicated by in vitro and early human data. In the SUDOCU study, PanACEA evaluated sutezolid together with a novel backbone, which has the potential to be a universal regimen for drug sensitive and drug resistant TB. PanACEA anticipates that SUDOCU will identify the optimal dose of sutezolid that provides the best efficacy, at acceptable safety, to be used in follow-up large-scale clinical trials.
We are currently, completing follow-up and checking all samples and data collected. In the analysis stage, we will deploy the most innovative and advanced PK-PD methods to describe the exposure-response relationship of sutezolid.
Ideally, we aim to report a target plasma concentration and an optimal dose of sutezolid as soon as possible!
Dr. rer. nat. Petra Gross-Demel is a scientist and clinical project manager at the Division of Infectious Diseases and Tropical Medicine of the LMU Munich. Petra is part of the development team managing phase II studies of the new investigational antibiotic BTZ-043 for tuberculosis.
Petra has been working for more than 20 years in clinical development at Sandoz/Novartis and in a CRO. As a globally acting Clinical Research Manager she managed phase I and III studies and developed global clinical program designs of superiority- pharmacokinetic-, bioequivalence-, non-inferiority, equivalence-studies including compilation or review of clinical and bioanalytical protocols, ICF, CRF, validation and bioanalytical reports under consideration of drug metabolism.
The St Andrews group’s most recent paper has been published as a perspective piece in the International Journal of Tuberculosis and Lung Disease.The collaboration between the Schools of Medicine, Applied Mathematics and Computer Science provides an overview of the different types of model that can be applied to tuberculosis clinical trials. Importantly, it provides a new insight on mechanistic models that can explore the interaction between pathogens, immune samples and the local environment including antibiotic concentrations. Tuberculosis is still one of the top 10 causes of death worldwide, this approach could allow patient level simulations and, ultimately, open the prospect of conducting a virtual clinical trial and help us choose between potential new regimens to test.
In the afternoon of 20th of February a ninety minutes interactive workshop on community engagement was held. The inspiring Erica Sanga, Community Engagement Coordinator at NIMR Mwanza, Tanzania, led the workshop.
During this workshop, participants from different sites shared their experiences and challenges on community engagement activities. Participants discussed their best practices for successful engagement of community stakeholders in SimpliciTB and plans to extend engagement to other (new) sites under the PanACEA Consortium with peer-to-peer guidance and training.
Special emphasis was put on engagement of study participants, their families, and other key community stakeholders, already early in the research process. This also includes improving research literacy and dialogue about the trial with key stakeholders at all levels.
Delegates from all of our collaborators in SimpliciTB TB travelled from across the world to attend the annual face to face General Assembly (GA) meeting in Mbeya, Tanzania. Trial progress was reported, with a focus on recruitment and medical monitoring. An important development was the launch of the Capacity Development programme that allows members of the consortium to bid for funds to develop sites across Africa, for training and for innovative seed-corn projects.
The GA also decided to add Uganda Case Western Reserve University Research Collaboration (Uganda) and Kibong’oto Infectious Disease Hospital (Tanzania) to the consortium.
Dr Erica Sanga from the National Institute Medical Research, Mwanza Medical Research Centre (NIMR-MMRC) presented and facilitated an interactive workshop on Community Engagement and Good Participatory Practices in TB Trials (GPP-TB). Engaging the community who suffer the effects of tuberculosis is very important for the consortium and this workshop helped to give everyone the tools necessary to reach out to local communities and communicate the true nature of the disease.
For the 10th annual face to face meeting the PanACEA consortium came together in Mbeya, Tanzania, on 19-20 February 2020. This year our partner Mbeya Medical Research Centre (NIMR MMRC) hosted the event. The warm hospitality and great organisation of the team made for a very positive meeting environment.
We were off to a great start with a number of workshops held before the meeting by our so called Expertise Cores. Patrick Phillips and Molly (Xue) Gong from the Statistics Core led workshops for statisticians and non-statisticians alike. The Biomarkers Core had a full program of presentations about ongoing MBLA research, discussions on treatment response biomarkers and new plans for biomarkers data analysis and modelling. Robert Hunt from the Microbiology Core gave a hands-on workshop with troubleshooting and sharing good practice.
The Annual Meeting was opened on Wednesday by the Honourable Deputy Minister Dr. Faustine Ndugulile of the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDGEC), together with Dr. Nyanda Ntinginya, director of NIMR MMRC, Prof. Yunus Mgaya, director of NIMR, Dr. Deodatus, chairman of the NIMR council and Martin Boeree Coordinator of PanACEA. Another guest of honour at the meeting was Dr. Christian Lienhardt, chair of the Scientific Advisory Board of PanACEA.
The first day the consortium updated eachother on project activities and progress. The BTZ043 trial is steadily enrolling; preparations for the SUDOCU trial are progressing; and the operationalization of the PHENORIF trial has started. The Expertise Cores each gave an extensive update on their progress as well. We ended the day with discussion about the current and future PanACEA scientific program.
The second day was dedicated to research projects not or only indirectly related to PanACEA. Some of the clinical trial sites showed impressive scientific and clinical development since joining PanACEA. This was confirmed by the results of a recent questionnaire about capacity development and leadership that Stellah Mpagama and Nyanda Ntinginya conducted and presented.
Monday 9th of December the PanACEA General Assembly (GA) met again for its quarterly assembly to report and discuss the progress of the project.
The first phase of the BTZ043 trial has started at the end of November at UCTLI and TASK Applied Science. Preparations for the SUDOCU and PHENORIF trials are progressing.
Next time, the GA will meet face-to-face at the Annual Meeting in Mbeya, Tanzania on 18th and 19th of February 2020. On this occasion Investigator’s meetings will be held for the BTZ043, SUDOCU and PHENORIF trials. In addition, several of the Expertise Cores are organizing workshops for capacity development purposes. The Cores will present updates about other planned activities at the Annual Meeting.
The new drug substance BTZ043 is being tested on patients for the first time in a Phase II study performed by the PanACEA consortium. The trial is carried out in Cape Town, South Africa at TASK Applied Science Clinical Research Centre and the University of Cape Town Lung Institute (UCTLI).
The study is funded by the German Federal Ministry of Education and Research (BMBF) and the European and Developing Countries Clinical Trials Partnership (EDCTP).
BTZ043 was discovered at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena. Since 2014, the new chemical entity has been developed in a consortium of scientists from the Leibniz-HKI and the Tropical In-stitute at the Hospital of the LMU Munich within the framework of the German Center for Infection Research (DZIF).
“Following the promising results of the Phase I study in Germany, we see a great chance that the good tolerability of BTZ043 will be confirmed in the treatment of tuberculosis patients. We are confident that we will also see good results in the first efficacy data.” Says Professor Michael Hoelscher, who is leading the Phase II study. If BTZ043 proves to be safe and effective in the current study, this would be a major step in the development of a new drug.
LMU press release
Clinical trial registration
We are pleased to announce that our consortium has added two trials to its portfolio. The SUDOCU and PHENORIF trials replace the Q203 study that was initially planned in the Grant Agreement. The trials will take place in South Africa and Tanzania in 2020.
Having established the maximum tolerated dose of rifampicin in the HIGHRIF trial, the purpose of the PHENORIF study is to further investigate the interaction potential of the higher dosages with a so-called metabolic phenotyping design. This method is a new concept in the PanACEA trial portfolio.
The objective of the SUDOCU trial is to identify the optimal dose of sutezolid in order to advance it into the novel STEPIIC design of PanACEA in which several combinations regimens are evaluated.
The PanACEA HIGHRIF trial that started in the first phase of PanACEA has continued in the current programme and has succesfully come to an end. The maximum tolerated dose of rifampicin was identified at 40mg/kg. Martin Boeree recently presented the results at The 50th Union World Conference on Lung Health in Hyderabad, India. The publication will follow soon.