As TB Alliance acknowledges its 20th year, we remain committed to advancing new cures and meeting the aspirations of those who gathered in Cape Town to demand a better future for those who suffer from TB. Read from our 20 Stories for 20 Years series below:
Late in 2005, TB Alliance signed an agreement with Bayer Healthcare AG to study moxifloxacin for potential use in new and improve tuberculosis therapies. At the time, the drug had been used off-label by health providers attempting to treat drug-resistant forms of TB and the possibility emerged that a moxifloxacin-containing regimen could shorten TB therapy.
As a non-profit dedicated to improving TB treatments, TB Alliance began preparing to evaluate moxifloxacin in a Phase 3 trial. However, it had been decades since such a study had been conducted for a new TB drug and regulatory standards had changed. What would it require to carry out a Phase 3 TB drug trial in the 21st century?
Beginning in 2006, TB Alliance set out to answer that question and build a plan to launch the first Phase 3 trial of a TB drug in decades. The stream of work that begun continues to inform cutting-edge TB drug research.
Conducting a Phase 3 trial of new TB regimens – in this case, containing moxifloxacin – would require many site locations across different continents. These sites had to have advanced scientific and technical capabilities and trained staff. They had to be compliant with standards of International Conference on Harmonization (ICH), Good Clinical Practice (GCP), and Good Laboratory Practice (GLP). They needed adequate pharmacy facilities and data management infrastructure. They also had to be located in areas with high TB burdens, which generally meant low resource settings.
From 2006 – 2008, TB Alliance evaluated 84 clinical trial sites and 72 associated mycobacteriology laboratories in 39 countries. The high-level results of this clinical trial site evaluation program were published in the International Journal of Tuberculosis and Lung Disease. This exercise concluded that developing adequate capacity to fully evaluate the clinical stage TB compounds under development at the time would require significant capacity-building efforts.
Of the 84 sites evaluated, 50% were judged capable of being ready within 6 months, 32.1% in 6–12 months and 14.3% in 1–2 years. Of the 72 mycobacteriology laboratories, 27.8% could be made ready within 6 months, 37.5% within 6–12 months and 27.8% within 1–2 years.
CONCLUSION: This survey indicates that developing adequate capacity to fully evaluate the compounds now in the clinical phases of development will require signify - cant capacity-building efforts.
The site evaluation program identified specific issues at potential trial sites that needed to be addressed in order for sites to meet the standards required to host late-stage TB trials. In some cases, TB Alliance worked with sites to help them prepare and address identified gaps. At the same time, it continued development work on moxifloxacin.
By 2009, TB Alliance and its partners began enrolment in the REMoxTB study –the Phase 3 trial testing four-month moxifloxacin-containing regimens for drug-sensitive TB. Due to extensive work and investment by TB Alliance and other stakeholders, there existed a growing network of capable sites to support the trial. REMoxTB launched in January 2009 and continued to add sites around the world throughout the course of the trial. The trial built global research capacity while investigating moxifloxacin’s potential to shorten therapy. Ultimately, the trial spanned 50 sites across nine countries.
While the trial did result in shortened TB treatment, it did yield valuable findings that informed the future study of moxifloxacin. Further it laid the foundation for 21st century TB drug research, proving that Phase 3 trials of TB therapies could be conducted to modern standards, and TB Alliance was capable of doing so.
More than a decade later, many of the core sites identified and developed as part of TB Alliance clinical trial site evaluation study are known as leading global centers for TB research. Local researchers have emerged to be among foremost experts in TB drug development. And, as the global portfolio of TB drug research has grown, so too has the global capacity to conduct such work – both of which are dynamics TB Alliance and the entire TB research community hope and work tirelessly to see continue.