The first ever treatment for preventing a group of viruses from causing potentially lethal infections has been tested in a phase I clinical trial, and was found to be safe and able to neutralise the viruses, according to results from 40 patients published in The Lancet Infectious Diseases journal.
Henipaviruses are an emerging group of viruses with pandemic potential, but no approved vaccines or treatments exist to prevent or treat the life-threatening infections they cause.
The trial was conducted in healthy participants and further trials will be needed to demonstrate its efficacy in infected patients.
Hendra virus and Nipah virus are two closely related RNA henipaviruses that emerged in 1994 and 1998 respectively. Flying foxes, a type of fruit bat, appear to be the major natural reservoir hosts for henipaviruses. A mortality rate of 57% has been observed from seven known cases of Hendra virus in Australia, while 373 fatalities from Nipah virus have been reported in south and southeast Asia between 1998 and 2018.
Although the number of outbreaks has been small so far, Henipavirus diseases have been placed on the WHO list of diseases with epidemic potential that are a priority for research because there are no, or insufficient, countermeasures.
Nipah virus has the potential to mutate rapidly, and human-to-human transmission is possible, raising concerns of pandemic potential.
The monoclonal antibody m102.4 has successfully neutralised henipaviruses in previous experiments with non-human primates. It binds to proteins on the surface of virus cells that would normally allow the virus to gain access to host cells and cause infection. The antibody has been available since 2010 for compassionate emergency use in Australia for people exposed to Hendra virus, but the current study is the world’s first clinical trial to assess its safety in humans and to determine its fate as it travels through the body.
Laboratory experiments were also used to test the ability of the antibody to neutralise the viruses after it had been circulating in the body.
The study was randomised, double blinded and placebo-controlled. 40 eligible adults aged 18 to 50 were randomly assigned to five different groups: four groups receiving the antibody in single doses that escalated from 1mg/kg in the first group to 20mg/kg for the fourth group, and the fifth group receiving two doses of 20mg/kg. In each group, six participants received the antibody and two received a saline placebo.
Overall, the doses of m102.4 used in the study were found to be safe and well tolerated.
Dr Elliott Geoffrey Playford from Princess Alexandra Hospital, Australia, said: “Given the high death rate from infection by henipaviruses, their ability to cause infection in multiple organs including the brain, and their unique ability to spread to humans from bats via a wide range of animal species including horses and dogs, doctors need a safe way to neutralise them.
“Our results are the first to confirm that administering an antibody that binds to the virus is safe, making it the most promising therapeutic option to date for addressing this unmet medical need.”
Dr Hossain Sazzad from the University of New South Wales, Australia, said: “Further evaluation of efficacy of m102.4 in established clinical infection— which was beyond the scope of the small-scale phase 1 trial done by Playford and colleagues—will be crucial.”