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REMoxTB trial results confirm moxifloxacin safety but not shortened tuberculosis treatment

8 September 2014

The results of REMoxTB, a phase III global clinical trial of new tuberculosis drug regimens, were presented Sunday 7 September 2014 at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy and published in the New England Journal of Medicine. The trial was led by Prof. Stephen H. Gillespie (St. Andrews University, Scotland) and conducted mainly in Africa (approximately 70% of patients).

The sponsor of the trial, the TB Alliance, stated in its press release that replacing one of the drugs in the standard six-month treatment regimen with moxifloxacin “did not allow the treatment time for tuberculosis (TB) patients to be shortened to four months”. “While the experimental regimens initially killed more TB bacteria than the standard regimen, patients receiving those shortened regimens were more likely to relapse than those taking the standard treatment.”

Prof. Charles Mgone, EDCTP Executive Director: “A shorter treatment regimen would have great significance for individual patients and TB care programmes alike. Unfortunately, this goal has not been achieved by the REMoxTB trial. However, it demonstrates what can be achieved in global health through partnerships and international collaboration. It is also gratifying to note that in this trial that took place in several countries in Africa, Asia and Latin America, African researchers recruited the majority of patients. As such it is a showcase of increased African capacity to undertake GCP-compliant trials.”

REMox TB trial

REMox TB is a three-arm, double-blind Phase III study in which moxifloxacin substituted for two different drugs in the current first-line standard TB therapy, ethambutol and isoniazid, and was administered for a total of four months.

REMox TB aimed to determine whether either of these two new, four-month regimens was not-inferior to standard six-month therapy in terms of failure and relapse. The trial enrolled 1,931 patients at 50 sites in nine countries: China, India, Kenya, Malaysia, Mexico, Tanzania, South Africa, and Zambia.

As part of the study, the capacity of African clinical trial centres to perform studies to the highest international regulatory standard was significantly enlarged in Tanzania (Moshi and Mbeya), Kenya (Nairobi), Zambia (Lusaka) and at several sites in South Africa. Training has been an integral part of the project; a strong team provided training in Good Clinical Practice and Good Clinical Laboratory Practice to sites on a regular basis.

At the completion of recruitment for the trial in 2012, Prof. Gillespie pointed out the long journey: ”The project started in 2008 and without the support of the TB Alliance and EDCTP this milestone could not have been reached. Developing the systems for the trial and managing the multiplicity of ethical review boards and national regulators, making translations into multiple languages, delivering drugs to a range of high burden countries to a defined standard have proved to be an enormous challenge, but the REMox TB team has worked tirelessly to achieve this complex project. Let us also recognize the considerable contribution of the patients who consented to be part of the trial.”

The REMOX TB study is registered with ClinicalTrials.gov under number NCT00864383 and with the Pan African Clinical Trials Registry under number: PACTR201110000124315.

Funding

The study was funded by the Bill & Melinda Gates Foundation, EDCTP, Irish Aid, the Medical Research Council United Kingdom (MRC UK), the United Kingdom Department for International Development (DIFID), and the United States Agency for International Development (USAID).

Via EDCTP, contributions were made by the Netherlands-African Partnership for Capacity Development and Clinical Interventions against Poverty-Related Diseases (NACCAP-WOTRO) and, again, the Bill & Melinda Gates Foundation and MRC UK.The pharmaceutical companies Bayer Healthcare AG and Sanofi provided the trial drugs and other support.

EDCTP has contributed a total of €9.7 million to REMox TB of a total project value of approximately €28 million.

PanACEA

The African branch of the REMox TB study is part of the Pan African Consortium for Evaluation of Anti-tuberculosis Antibiotics (PanACEA). EDCTP brokered the establishment of the PanACEA network which comprises six European research organisations, twelve sub-Saharan clinical trial sites, and three pharmaceutical companies.

The consortium developed a collaborative approach across the participating groups in the conduct of regulatory standard clinical trials for three TB drugs. Moreover, the groups collaborate in capacity development in sub-Saharan Africa for the conduct of ICH-GCP and GCLP compliant clinical trials.

The total funding of this consortium is €48,280,404 with a contribution of €17,264,270 from EDCTP.

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