The results of the safety study conducted with 1,208 non-parasitological-confirmed seropositive participants confirmed the favourable safety profile of acoziborole for the treatment of T.b.gambiense sleeping sickness. The recruitment of seropositive participants in StrogHAT – an intervention study to evaluate acoziborole’s safety, effectiveness, and feasibility – started in northern Equateur province in the Democratic Republic of the Congo. The recruitment of children with T.b.gambiense sleeping sickness aged between 1 and 14 years old also began in the second step of the ACOZI-KIDS study.

The recruitment and four-month follow-up of adult patients with non-parasitologically confirmed human African trypanosomiasis caused by T.b. gambiense were both completed, with 1208 participants treated with acoziborole. Data cleaning has been initiated and study results are expected in the first quarter of 2024. In parallel, nine children weighing between 30 kg and 40 kg and treated with 640 mg of acoziborole completed the 12-month follow-up visit. The study will resume in 2024 with the recruitment of children weighing 10 kg to 40 kg.

The results of the Phase II/III trial in adult patients with human African trypanosomiasis caused by T.b. gambiense (g-HAT) were published in the journal Lancet Infectious Diseases in November 2022. Extensive coverage across local and international media followed, with many experts hailing the new treatment as showing promise to sustainably eliminate the disease.

The clinical trial assessing the safety and tolerability of acoziborole in g-HAT seropositive, non-parasitologically confirmed research participants continued through 2022 with more than 1000 participants recruited by the end of the year. In parallel, the paediatric clinical trial for children diagnosed with g-HAT was initiated. Nine children weighing between 30 kg and 40 kg were each treated with 640 mg of acoziborole.

Data from the pivotal Phase II/III clinical trial in adult patients with human African trypanosomiasis caused by T.b. gambiense (g-HAT) was analysed in 2021, followed by completion of the clinical study report.   

Work on the extended use of acoziborole continued with the launch of a clinical trial assessing the safety and tolerability of acoziborole in g-HAT seropositive, non-parasitologically confirmed research participants. The first participants were treated in late 2021, while the paediatric clinical trial was submitted for regulatory authority and ethics committee review. 

In August 2020, the 18-month post-treatment follow-up was completed for all 208 patients recruited in the Democratic Republic of Congo and Guinea for DNDi’s pivotal Phase II/III clinical trial, which evaluated the safety and efficacy of acoziborole as a potential treatment for both Stage 1 and Stage 2 human African trypanosomiasis caused by T.b. gambiense (g-HAT). A final study report will be prepared in 2021. 

Additional non-clinical studies to meet European Medicines Agency and US Food and Drug Administration requirements were also carried out. Preparatory work to launch two g-HAT seropositive and paediatric clinical studies will continue in 2021.

The enrolment of 208 patients was completed in March 2019. The clinical study will be finished at the end of 2020 once 18-month post-treatment follow-up has been completed for all patients at clinical sites in the Democratic Republic of Congo and Guinea. In the interim, non-clinical studies to meet EMA and US FDA requirements will be carried out. 

In 2018, recruitment of patients continued with 189 patients enrolled by the end of the year, including 155 patients with late stage 2 disease, and the target enrolment of 210 patients reached by March 2019. Four new clinical sites in the Democratic Republic of Congo (DRC) were added to the already active sites (Katanda, Isangi, Roi Baudouin Hospital in Kinshasa, Dipumba, N’gandajika, Masi Manimba, Kwamouth, Bandundu) and a new site was opened in Guinea (Dubreka).

Recruitment continued in the DR Congo with the inclusion of 76 patients (out of a target of 210) at eight clinical sites, including new sites in Bandundu and Kinshasa (Roi Baudouin Hospital), in addition to Katanda, Isangi, Dipumba, N’gandajika, Masi Manimba, and Kwamouth. One site (Bolobo) was closed in December 2017. Three more sites will open in 2018, including one in Guinea.

A pivotal Phase II/III trial started in the last quarter of 2016. Seven study sites – Katanda, Isangi, Dipumba, Ngandajika, Masi Manimba, Kwamouth, and Bolobo – were initiated in Democratic Republic of Congo (DRC). Eleven patients (out of a target 350) had been recruited by the end of 2016.

The Phase I study with acoziborole was conducted and completed in 2015 in France. It assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of acoziborole after single oral ascending doses in 128 healthy human volunteers of sub-Saharan origin. It allowed for the therapeutic dose to be determined at 960 mg administered once as three tablets, with a favourable safety profile. As the drug has a long half-life (400 hours), the study was extended to ensure extensive safety monitoring of the healthy volunteers up to 210 days. This pharmacological finding has the advantage of translating into prolonged exposure with just one dose. These Phase I results confirm that the drug penetrates the brain, which is crucial to treat the late stage of the disease, where the parasite crosses the blood-brain barrier and kills patients if no treatment is given. Based on the results of this study, presented at the 9th European Congress on Tropical Medicine and International Health (ECTMIH) in September 2015, the single dose treatment will be tested in patients with stage 2 g-HAT in a Phase II/III trial, planned to start in the Democratic Republic of the Congo in 2016. The study will use several sites already active in fexinidazole development with addition of new sites selected from high-prevalence g-HAT areas. Patients will be followed up for 18 months after treatment to ensure long-lasting cure, with a preliminary evaluation of data performed after the first 12 months.