Pune, India: Doctors Without Borders/ Médecins Sans Frontières (MSF) in collaboration with Indian Council for Medical Research (ICMR)- National AIDS Research Institute (NARI) and Department of Health Service, Government of Maharashtra is initiating two major clinical trials that aim at generating clinical evidence on the safety and efficacy of novel, short and all-oral regimens for the most difficult-to-treat strains of tuberculosis (TB). The trials are part of a UNITAID-funded transformative (multi-country) project called endTB, which aims to speed up and expand access to better treatments for drug-resistant forms of TB.
India accounts for 27% of the 10 million TB cases globally, of which an estimated 130,000 are multi-drug-resistant (MDR-TB). The current treatment of MDR-TB has a duration of 18-24 months for most patients; during the treatment, patients ingest more than 14,000 pills and, in some cases have to endure painful daily injections for six to eight months, which has terrible side effects such as acute psychosis and permanent deafness. Most Indian MDR-TB patients prefer to visit private practitioners of varying standards in desperate attempts to cure their disease, find treatment expensive, causing treatment interruptions.
The two clinical trials, namely (i) endTB & (ii) endTB-Q will use the new generation of TB drugs, which were developed after almost 50 years of draught of new anti-TB drug classes — bedaquiline and delamanid — to find radically shorter (6 or 9 months), more tolerable, injection-free treatments for MDR-TB.
“New generation drugs – bedaquiline and delamanid – represent a unique opportunity to improve MDR-TB treatment. These drugs have shown promising results when added to the standard, long and badly-tolerated MDR-TB treatment; however, we know little about how to optimise their use in the management of complex cases. Without further research, we are only scratching the surface and patients continue to suffer,” said Dr. Samiran Panda, Head, Epidemiology and Communicable Disease, ICMR, and Coordinating Principal Investigator, endTB Trials -India.
Clinical trial for fluoroquinolone-susceptible MDR-TB[1](endTB clinical trial)
This is a randomized and controlled Phase III clinical trial testing new and all oral 9-month regimens compared to the current standard of care for patients with MDR-TB that is susceptible to fluoroquinolones, the most effective drug class for drug-resistant TB. Each experimental regimen will contain at least one new drug, in combination with up to four companion drugs.
The control regimen is the local standard of care consistent with latest World Health Organisation (WHO) recommendations and may include new drugs if indicated. Randomization will be outcome adapted, means that the probability of being randomized to regimens changes as the outcomes are reported; as a result, more patients will be assigned to regimens that are producing better outcomes. The clinical trial is expected to enroll 750 patients at all selected sites in various countries.
Clinical trial for fluoroquinolone-resistant MDR-TB[2] (endTB-Q clinical trial)
A related parallel trial, endTB-Q is a randomized and controlled Phase III clinical trial testing a new and all-oral treatment regimen, compared to the current standard of care, against forms of MDR-TB that are also resistant to fluoroquinolones. This regimen – containing bedaquiline, delamanid, clofazimine, and linezolid – will be delivered for 6 or 9 months: the duration will be adapted to baseline disease characteristics and treatment response of each participant. The clinical trial is expected to enroll 324 patients.
“India has had low success rate – 48% of treating MDR-TB, as compared to 56% globally. India is contributing in global TB elimination efforts by generating more scientific evidence through these trials. Together, these two trials will revolutionize the treatment by identifying the most effective and less toxic all-oral, shorter (between six and nine months) treatment regimens against the deadliest forms of TB, ” said Dr Hanif Shaikh, India Coordinator, endTB Trials.
In India, the endTB trials will be run at two sites in Maharashtra – Pune and Mumbai. Today, the first patient has been enrolled in the trials at Aundh Chest Hospital in Pune – the first trial site activated in India. Approximately 220 patients are expected to be enrolled in the trials at the two sites by the end of 2021, by a team of over 30 medical and paramedical staff, working under the joint coordination of NARI and MSF. The Site Principal Investigators are Dr. Sandip Patil, Aundh Chest Hospital- Pune and Dr. Chetan Kumar Jain, Sarvodaya Hospital- Mumbai.
“Adding India into the multi-country trials was a crucial step that will help building robust evidence about the best therapeutic options for the hardest-to-treat TB patients from a high TB burden country. MSF, with its support to public health care, remains committed to offer a better treatment and a new hope to all MDR-TB patients, bringing innovation through research and contributing to India’s goal of eliminating TB by 2025,” said Dr Stobdan Kalon, MSF Medical Coordinator, India.
