Can the first new tuberculosis drugs in five decades make treatment faster and less dangerous for the hundreds of thousands of people living with drug-resistant strains of the world’s deadliest infectious disease?
A cross-border, cross-sectoral clinical trial has passed a major milestone on the road to answering that question.
On Oct. 18, the endTB consortium, a partnership between Partners In Health, Médecins sans Frontières, Interactive Research & Development and financial partner UNITAID, announced that 750 patient volunteers from four continents have enrolled in a trial that aims to find effective, safer, and shorter treatments for multidrug-resistant tuberculosis (MDR-TB), an airborne, infectious disease that no longer responds to standard medications.
Thanks to the diversity of the study population, the results will be relevant to a wide range of patients living with MDR-TB, said Carole Mitnick, professor of global health and social medicine in the Blavatnik Institute at Harvard Medical School and co-principal investigator of the trial. The results will be available in 2023.
“While all were sick with TB resistant to standard treatment, the study population included people from a range of racial and ethnic backgrounds and people affected by comorbidities that occur commonly with MDR-TB like HIV, hepatitis C, or diabetes. People with these conditions are often excluded from TB trials making it difficult for doctors to know how best to treat their patients,” Mitnick said.
Started in 2017, this phase 3 randomized controlled trial recruited 750 patients with MDR-TB from seven countries: Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa. The trial compares five new treatment regimens for MDR-TB containing two of the three new TB drugs developed in recent years, bedaquiline and delamanid, in combination with other existing oral TB drugs For nearly 50 years no new anti-TB drugs were developed, and those older drugs required regimens as long as two years. Now this new generation of drugs allow for the development of radically shorter, more tolerable, injection-free treatments for MDR-TB. “An old enemy of mankind, tuberculosis remains the deadliest infectious disease today. And MDR-TB is the most cruel and merciless version. The coming results of this trial could be lifechanging for more than 500,000 people suffering from MDR-TB, and may help to appropriately treat millions of patients—tomorrow and in decades to come,” said Lorenzo Guglielmetti, endTB project leader for Médecins sans Frontières and co-principal investigator of the trial.
“This is a significant milestone in Unitaid’s largest investment into TB. With sobering new data from the Global TB Report showing progress against TB slipping backwards for the first time in over a decade, new tools and treatments are more crucial than ever. The innovative multi-country endTB trial will not only benefit people with MDR-TB—a more complex and difficult to cure strain of TB—but it is also building long-term capacity in the countries that are managing this multi-faceted clinical trial,” said Philippe Duneton, executive director of UNITAID.
The researchers highlighted other factors that make this study noteworthy.
First, the trial uses innovative study design to increase the efficiency of the trial. Regulatory bodies had approved the individual medications, but the optimal combinations of these drugs were unknown. Rather than testing different drug regimens sequentially over a decade or longer, endTB applied adaptive randomization, thereby maximizing the number of patients who get well-performing experimental regimens. This allows for a relatively small sample size, requires fewer resources, and may enable dramatic improvements in treatment over short periods of time.
Second, enrollment is designed to benefit all. For example, endTB enrolled women and adolescents—groups that are often left out of clinical trials in an effort to protect them—to be sure that doctors have the data they need to best care for them. And the consortium helped train staff at clinical sites, thus enabling more research, faster recommendations, and better treatments in the future.
Lastly, it’s significant that enrollment was completed despite massive constraints related to the COVID-19 pandemic, which has paused hundreds of clinical trials. Universities, hospitals, labs, and others have been forced to stall or cancel research into illnesses ranging from cancer to rare diseases. Instead, the endTB consortium adapted and continued.
This clinical trial is part of the larger endTB project that was launched to revolutionize treatment for MDR-TB patients. Approximately 2,800 patients from 17 countries were enrolled in an observational study that produced strong evidence of the effectiveness of new drugs and further supports a rapid increase in access to these drugs. A second randomized controlled trial, called endTB-Q, is underway to study a 6-9 month regimen to treat the most resistant form of MDR-TB.
In addition, the endTB trial complements the TB-PRACTECAL clinical trial, also sponsored by Médecins sans Frontières, which include another newer drug called pretomanid to provide high-quality evidence on shorter, all-oral regimens. Ultimately, both address the critical need for increased treatment options—and access—for the approximately 500,000 people who fall sick each year with MDR-TB.
This story is adapted from an endTB news release.