Trial shows drug acoziborole cleanses body of African sleeping sickness parasites

A multicenter, open-label, phase II/III clinical trial was recently conducted to evaluate the efficacy and safety of the oral antimicrobial drug acoziborole in patients with human African trypanosomiasis (HAT). The trial findings have been published in Lancet infectious diseases.

To study: Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicenter, open-label, single-arm, phase 2/3 trial. Image Credit: Jackie Niam/Shutterstock.com

Background

HAT, also known as sleeping sickness, is a neglected tropical disease caused by the parasite Trypanosoma brucei gambiense, transmitted by the tsetse fly. HAT is endemic to sub-Saharan Africa, particularly in the Democratic Republic of the Congo.

HAT treatment approaches depend on the stage of the disease. In the early stage of the disease, an intramuscular injection of pentamidine is given to treat the infection. However, late-stage disease requires more potent treatment due to the presence of the parasite in the brain.

Late-stage HAT is conventionally treated with nifurtimox-eflornithine combination therapy (NECT), which requires hospital admission. Only one oral drug known as fexinidazole with a 10-day treatment regimen is currently available to treat late-stage HAT; however, it is not clear if this drug can reduce the severity of the disease.

The Drugs for Neglected Diseases initiative, in collaboration with Anacor Pharmaceuticals and Scynexis, has discovered another oral drug, acoziborole, for the treatment of late-stage HAT. In preclinical trials, acoziborole has been shown to be an effective antimicrobial against Trypanosoma brucei gambiense.

In the current phase II/III prospective, open-label, multicenter clinical study, scientists determine the therapeutic efficacy and safety of acoziborole in patients with laboratory-confirmed HAT.

Study design

A total of 208 patients aged 15 years or older were recruited from ten hospitals in the Democratic Republic of the Congo. Of all the participants, 167 had late-stage HAT and 41 had early-stage HAT.

Participants were administered a single 960 mg dose of acoziborole orally. The patients were observed for 15 days in the hospital. After hospital discharge, they were followed up at three, six, 12, and 18 months.

Therapeutic efficacy of acoziborole

In 159 of 167 patients with late-stage HAT, the treatment success rate at 18 months was estimated to be 95%. Treatment success was defined as cure or probable cure, reflecting the absence of trypanosomes and less than 20 white blood cell (WBC) counts per μL of cerebrospinal fluid.

Considering the evaluable population of 162 patients, the 18-month treatment success rate was estimated at 98% in 159 patients. In addition, similar treatment success rates were observed at six, 12, and 18 months, comparable to those previously observed for conventional NECT, regardless of disease severity.

Treatment failure at 18 months occurred in eight patients with late-stage HAT and included three cases of relapse, four deaths, and one case lost to follow-up.

Safety profile of treatment with acoziborole

A gradual reduction in the frequency of symptoms was observed from day 15 after treatment. However, about 75% of treated patients experienced 600 treatment-emergent adversities. Of these side effects, 93% were mild or moderate and 7% were severe in intensity. The most frequently reported adversities were pain and procedural headache, headache, fever, and malaria.

About 14% of patients experienced 38 medication-related treatment-emergent adversities that were mild or moderate in intensity. The most commonly reported adversities were fever and asthenia, also known as lack of energy.

Incidental pregnancies were detected in seven women within six months of treatment. However, no drug-related complications were observed in either the mothers or the babies.

A total of four deaths occurred in the treated population. However, none of the deaths were related to treatment or disease.

Importance of the study

The results of the study indicate that acoziborole is a safe and effective drug for the treatment of adolescent and adult patients with mild, moderate, or severe HAT. The main benefit of this treatment is that only a single oral dose of acoziborole is sufficient to treat patients with HAT. This treatment regimen would be beneficial for patients living in remote locations who do not have immediate access to healthcare facilities.

Another advantage is that acoziborole treatment does not require routine lumbar puncture procedures at diagnosis and during follow-up. However, this procedure requires trained personnel and is associated with health complications. In addition, the procedure can cause anxiety in patients.