2013 Annual Report
Planning for Phase 3

Primary endpoints met in NC-002 trial; planning for a Phase 3 trial of PaMZ.

In NC-002, a clinical trial that was the first of its kind, the novel drug combination PaMZ met its primary endpoint. TB Alliance is now planning for a global Phase 3 registration trial of the PaMZ regimen, consisting of PA-824, moxifloxacin, and pyrazinamide. Data from NC-002 is still under evaluation. The full results of the study will be available in 2014.

The PaMZ regimen has the potential to shorten and simplify treatment for TB and to be compatible with commonly used antiretrovirals. Importantly, the NC-002 study was the first to treat patients with both drug-sensitive and some forms of MDR-TB — a paradigm shift, and potentially a significant advance, in care and management of the disease.

NC-002 was an eight-week Phase 2b clinical trial that enrolled more than 200 patients, and took place at eight sites in South Africa and Tanzania.

NC-002 not only delivered exciting results, but evidenced TB Alliance's unified development pathway — a development plan designed to accelerate the timeline to deliver impactful novel treatments. As part of this innovative pathway, PaMZ is being tested to both treat drug-sensitive and some forms of drug-resistant disease in a fraction of the time it would otherwise take. By ensuring this regimen undergoes Phase 3 testing, the appropriate data can be collected so that, upon launch, it can achieve uptake and positive impact on public health.

NC-002 was an eight-week Phase 2b clinical trial that enrolled more than 200 patients, and took place at eight sites in South Africa and Tanzania. The trial was conducted based on the TB Alliance's two-week New Combination 1 trial, or NC-001, completed in 2011, which was the first study to test novel TB drugs in combination. Importantly, the NC-002 trial advanced the technical and human infrastructure to conduct TB clinical development. The study relied on collecting information from multiple labs, and also supported Community Engagement work, significantly scaling up global research capacity.

Proceeding to Phase 2B

A novel drug combination advances, based on the results of the New Combination 3 (NC-003) trial.

NC-003 was a Phase 2a trial designed to identify combination therapies for continued development that had the potential to further shorten treatment of TB and MDR-TB. The regimens tested in the two-week trial included various combinations of PA-824 (Pa), bedaquiline (J), pyrazinamide (Z), and clofazamine. NC-003 was successful in meeting its milestones, and identified bedaquiline + PA-824 + pyrazinamide (JPaZ) as a promising combination regimen. JPaZ will now be advanced to a Phase 2b two-month trial.

The JPaZ regimen includes two important new drugs (PA-824 and bedaquiline), bringing the world closer to a totally novel universal regimen. PA-824 is under development as part of the JPaZ regimen and also as part of the PaMZ program, and bedaquiline was FDA approved in late 2012 as an add-on to the current 18-month MDR-TB regimen. Importantly, JPaZ shows potential to create a shorter, completely oral regimen that could dramatically expand the number of patients able to benefit from bedaquiline.

NC-003 also tested pyrazinamide and clofazimine individually to answer important questions raised by the field. Although pyrazinamide is included in the first-line regimen and clofazimine is being tested and is used off-label to treat MDR-TB, the early bactericidal activity (EBA) of pyrazinamide and clofazimine has never been established. Full results of the NC-003 trial will be made available in 2014.

NC-003 was performed at two sites in South Africa and enrolled 105 patients with pulmonary TB.

Phase 3 Trial Completed

A trailblazing effort already achieves impact.

In 2013, TB Alliance and partners completed the REMox TB trial. The Phase 3 clinical trial tested the potential of a four-month moxifloxacin-containing treatment regimen to reduce the duration of TB therapy by a third — from 6 months to 4 months. REMox TB was a trailblazer. Conducted at 50 sites in 9 countries, it remains one of the largest and most robust TB clinical trials conducted in decades. Results are expected in 2014, but at the trial's completion, it's important to examine the impact REMox TB has already achieved.

Prior to the initiation of REMox TB, there was little infrastructure and capacity to support late-stage clinical research. Efforts to map and build local capacity to conduct such research were part of the early stages of REMox TB. Today, several research sites that were among the first to enroll patients into REMox TB have advanced their capacity and skills, and emerged as global leaders in TB clinical development. Promising treatments undergoing development today can be brought more efficiently through the last and most difficult stages of testing, in part, because of the capacity REMox TB helped build.

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Any [advance] that reduces the time span a patient is on medication is definitely welcome.
— Dr Joseph Sitieni
Ministry of Health, Kenya

In addition to determining the viability of a new, shorter treatment regimen, REMox TB will also yield results that will help enhance the understanding of several key areas of clinical TB research, including the predictive capacity of earlier stage trials. REMox TB has also served as a springboard for the development of the deepest and most complete engagement of communities in TB research to date, programs which remain pillars of TB Alliance clinical development.

Click here to read about the engagement of community in REMox TB

To ensure rapid and effective adoption and uptake of new products, key decision makers must be engaged and begin planning well in advance of a product's approval. REMox TB helped make TB research and the promise of new tools a reality to a variety of key stakeholders. The continuous progress of REMox TB enabled the proactive engagement of those required to implement new treatments, including regulatory bodies, National Treatment programs, product manufacturers, and communities. If REMox TB results are positive, the efforts to activate these relationships and processes will come to define the next stage in the pursuit of the first shortening of treatment for drug-sensitive TB in nearly a half century.