Bihar to host clinical trial on revolutionary tablet for kala-azar
The phase-II trial on LXE 408 is set to begin at ICMR’s Rajendra Memorial Research Institute of Medical Sciences (RMRIMS) in Patna and the Kala Azar Medical and Research Centre, Muzaffarpur, by July,
PATNA Come July, Bihar will host the Phase II clinical study on a new kala-azar(KA) drug, code-named ‘LXE 408’, a simple tablet, which will change the way patients are now treated through injectables, said Fabiana Alves, Leishmaniasis and Mycetoma cluster director of the Drugs for Neglected Diseases initiative (DNDi), a Geneva-based organisation that has collaborated with a multi-national pharmaceutical firm in its research on the drug.
“We will begin the phase-II trial on LXE 408 at the Indian Council of Medical Research (ICMR)’s Rajendra Memorial Research Institute of Medical Sciences (RMRIMS) in Patna and the Kala Azar Medical and Research Centre, Muzaffarpur, hopefully by July,” said Alves.
The DNDi sees this oral drug as the future treatment for kala-azar or visceral leishmaniasis (VL), a disease caused by an infection with a protozoan parasite that enters the body through the bite of an infected female sand fly or ‘balu makhi’, as it is called in local parlance. The disease is characterised by irregular bouts of fever, weight loss, anaemia, and enlargement of the spleen and liver that shows up as a pot belly in the patient. If not treated, the disease can be fatal.
RMRIMS director Dr Krishna Pandey, who is one of the principal investigators of the study, said the new tablet would herald a revolution in the treatment of kala-azar cases. “We mostly have injectables, requiring in-patient hospitalisation for the treatment of kala-azar so far, but will now have a tablet,” he said.
“In comparison to the more prevalent present-day kala-azar drug, AmBisome, an intravenous drug that has to be refrigerated and administered through a trained nurse, the LXE 408 is a more user-friendly drug as it is an oral medication and can be kept closer to the community, especially in rural areas, where people have poor access to healthcare,” said Alves.
The phase I trial of the drug on healthy individuals was done in the USA.
The commencement of phase II trial in India depends upon certain clearances on foreign funds from the government.
The study, she said, would continue for around 18 months and revolve around the duration of treatment, a patient’s tolerance to the medication, the optimum dose required to kill the leishmaniasis parasite, the safety of the drug, etc.
“We had enrolled 88 healthy volunteers in the USA during the phase I trial on healthy individuals that were completed recently after it began in 2018-19. We are now targeting around 100 patients of kala-azar during the phase II trial of the drug in Patna and Muzaffarpur,” said Alves.
Researchers, however, said that enrolling as many patients would be a challenge, given that the disease burden has come down in Bihar, the most endemic kala-azar state after Jharkhand, Uttar Pradesh, and West Bengal.
Bihar reported 163 of India’s total 215 cases of kala-azar and four of the five deaths in the last financial year (till March 2022), as per provisional data on the website of the National Center for Vector-Borne Diseases Control of the directorate general of health services, ministry of health and family welfare. Jharkhand had 44 cases and one death, Uttar Pradesh six cases, and West Bengal two during the same period.
Bihar’s kala azar scenario was much different in 2014 when it accounted for almost 85% of the country’s total 9,241 cases and 10 of the 11 deaths. Jharkhand then had 937 cases, West Bengal 668 cases and one death, Uttar Pradesh 11 cases, Sikkim 5, Uttarakhand 4, and Assam 1.
Last year, Bihar accounted for nearly 70% of India’s 1,395 cases of kala-azar, 59% of the total 773 cases of post-kala-azar dermal leishmaniasis (PKDL), and 84% of the country’s nearly 95 cases of human immunodeficiency virus infection with visceral leishmaniasis (HIV-VL), as per government data available till 2021.
“Along with Bihar, we plan to have clinical studies in Africa and Latin America so that we can tap all kala-azar endemic areas in the world for clinical trials. We are designing the study for Africa and it is likely to begin next year. Initiating the study in Latin America will take more time,” said Alves.
After five missed deadlines, the Centre has now set a plan to eliminate KA by the end of this year.
“Many Indians are also known to have developed resistance to the first known anti-kala-azar drug sodium stibogluconate, which was used in India earlier by the administration through intramuscular injection. Other medications, including liposomal amphotericin B, an intravenous drug, have some side effects or are not as easy to administer and require in-patient hospitaliation,” said Dr Pandey.
“Some studies have suggested that a few patients have developed resistance to liposomal amphotericin B. There are also reports of patients developing resistance or complications to Miltefosine (the first oral drug for leishmaniasis), an anti-cancer drug used as a topical application for the skin metastasis of breast cancer, and also to treat HIV-VL and PKDL, a complication of visceral leishmaniasis,” he added.
“Against this background, the LXE 408 tablet is being seen as a landmark and the future drug for the treatment of kala-azar,” said Dr. Pandey.