A single dose of oral acoziborole resulted in a greater than 95% cure or probable cure rate for human African trypanosomiasis (HAT), also known as sleeping sickness, according to results from a clinical trial testing a one-dose experimental drug.
The drug has “the potential to revolutionize treatment” for the disease, which remains endemic in sub-Saharan Africa, said Antoine Tarral, MD, head of the human African trypanosomiasis clinical program at the Drugs for Neglected Diseases initiative, based in Geneva, and senior author of the study, in a press release.
he told this news organization. “It’s the first drug we can use without hospitalization. ... All the previous medications needed hospitalization, and therefore we could not treat the population early before they started expressing symptoms.”
The World Health Organization “has been working for decades for such a possibility to implement a new strategy for this disease,” Dr. Tarral said.
Current (2019) WHO guidelines recommend oral fexinidazole as first-line treatment for any stage of the disease. The 10-day course often requires hospitalization and skilled staff. Previous recommendations required disease-staging with cerebrospinal fluid (CSF) sampling and 7 days of intramuscular pentamidine for early-stage disease or nifurtimox-eflornithine combination therapy (NECT) with hospitalization for late-stage disease.
By contrast, acoziborole, which was codeveloped by the DND initiative and Sanofi, “is administered in a single dose and is effective across every stage of the disease, thereby eliminating the many barriers currently in place for people most vulnerable to the diseases, such as invasive treatments and long travel distances to a hospital or clinic, and opening the door to screen-and-treat approaches at the village level,” Dr. Tarral said in the statement.
“Today, and in the future, we will have less and less support to do this long and costly diagnostic process and treatment in the hospital,” he said in an interview. “This development means we can go for a simple test and a simple treatment, which means we can meet the WHO 2030 goal for ending transmission of this disease.”
Results from the multicenter, prospective, open-label, single-arm, noncomparative, phase 2/3 study were published in The Lancet.
Pragmatic study design
Sleeping sickness is caused by Trypanosoma brucei gambiense (gambiense HAT). It is transmitted by the tsetse fly and mostly fatal when left untreated.
The study enrolled 208 adults and adolescents (167 with late-stage, and 41 with early-stage or intermediate-stage disease) from 10 hospitals in the Democratic Republic of the Congo and Guinea. All patients were treated with acoziborole 960 mg – an unusual study design.
“Due to the substantial decline in incidence, enrolling patients with gambiense HAT into clinical trials is challenging,” the authors wrote. “Following advice from the European Medicines Agency, this study was designed as an open-label, single-arm trial with no comparator or control group.”
After 18 months of follow-up, treatment success, defined as absence of trypanosomes and less than 20 white blood cells per mcL of CSF, occurred in 159 (95.2%) of the late-stage patients, and 100% of the early- and intermediate-stage patients, “which was similar to the estimated historical results for NECT,” the authors noted.
Serious treatment-emergent adverse events were reported in 21 (10%) of patients, “but none of these events were considered drug-related,” they added.
The DND initiative and the WHO are currently nearing completion of a much larger, double-blind, placebo-controlled trial of acoziborole to “increase the safety database,” Dr. Tarral explained.
“Purists will say that acoziborole has not been evaluated according to current standards, because the study was not a randomized trial, there was no control group, and the number of participants was small,” said Jacques Pépin, MD, from the University of Sherbrooke (Que.), in a linked commentary.
“But these were difficult challenges to overcome, considering the drastic reduction in the number of patients with HAT and dispersion over a vast territory, particularly in the Democratic Republic of the Congo. For these reasons, the authors took a pragmatic approach instead,” he wrote.