Develop and register acoziborole as a new, single-dose, oral treatment for T.b. gambiense sleeping sickness
current phase of drug development
updated 16 Feb 2023
In late 2009, acoziborole was selected as a pre-clinical candidate to treat sleeping sickness caused by T.b. gambiense. DNDi’s own lead optimization project led to the selection, starting with an initial hit identified in the Anacor chemical library. In 2012, acoziborole became the first new chemical entity to enter clinical development from DNDi’s own lead optimization programme.
The delivery of fexinidazole, a new all-oral treatment for Stage 1 and Stage 2 sleeping sickness, greatly improved therapeutic options for the disease. But the development of an additional oral drug, especially one that could be given as a one-day, single-dose treatment, could simplify administration and strengthen efforts towards sustained elimination of the disease.
Katey Owen, Director of Neglected Tropical Diseases, Bill & Melinda Gates Foundation
Fexinidazole is a true game-changer for sleeping sickness. If acoziborole, a single-dose treatment, is shown to be safe and effective, we’re hopeful it would provide national programmes an even better tool to help achieve global elimination goals.
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.
ACOZI-KIDS: Developing acoziborole for children
ACOZI-KIDS aims to develop and register acoziborole as a single-dose, oral treatment for children with Stage 1 and Stage 2 sleeping sickness caused by T.b.gambiense. The project brings together a consortium of European and African experts: DNDi, the National Control Programmes for Human African Trypanosomiasis (PNLTHA) of the Democratic Republic of Congo and Guinea, Epicentre, the Research Institute for Development (IRD), and the Nova University of Lisbon/Institute of Hygiene and Tropical Medicine (IHMT/NOVA).
News & resources
- 21 March 2023 - Sleeping sickness is nearing elimination. An experimental drug could help, ScienceNews
- 22 February 2023 - HAT Platform Newsletter No. 22
- 20 February 2023 - Un espoir pour éliminer la maladie du sommeil, RTS
- 10 February 2023 - Determination of the optimal single dose treatment for acoziborole, a novel drug for the treatment of human African trypanosomiasis: First-in-human study, Clinical Pharmacokinetics
- 27 January 2023 - Eliminating neglected diseases in Africa: there are good reasons for hope
- 15 January 2023 - Eliminar la enfermedad del sueño no es une quimera, La Razón
- 16 December 2022 - 2022 in review: Drug development milestones for tropical diseases, Pharmaceutical Technology
- 13 December 2022 - Comment éliminer la maladie du sommeil?, Telesud
- 2 December 2022 - With one dose, new drug may cure sleeping sickness. Could it also wipe it out?, NPR
- 1 December 2022 - New drug: Patients with sleeping sickness in Africa relieved, The Star
- 30 November 2022 - Un nouveau traitement fait espérer l’élimination de la maladie du sommeil, RFI
- 30 November 2022 - Drug clears sleeping sickness parasite from the body in clinical trial, New Scientist
- 30 November 2022 - Traitement de la maladie du sommeil : L’essai clinique d’un médicament à dose unique présente un taux réussite de 95%, 7 sur 7
- 30 November 2022 - Will a one-dose drug mean the end of sleeping sickness?, Medscape
- 30 November 2022 - Un nouveau traitement prometteur contre la maladie du sommeil, Libération
- 30 November 2022 - One dose of acoziborole led to cure of ‘sleeping sickness’ across disease stages, MedPage Today
- 30 November 2022 - Afrique : Acoziborole, étude d’un nouveau traitement oral et à dose unique, suscite l’espoir d’éliminer la maladie du sommeil, Actualité CD
- 30 November 2022 - New cure for sleeping sickness could eliminate ‘nightmare disease’, The Telegraph
- 30 November 2022 - El contagio de la enfermedad del sueño podría eliminarse en 2030 con una nueva dosis única, La Vanguardia
- 30 November 2022 - Un médicament fait espérer l’éradication de la maladie du sommeil, Le Monde
- 30 November 2022 - New single-dose drug 95 per cent effective against sleeping sickness in adults: Lancet study, Press Trust of India
- 30 November 2022 - Un médicament sans hospitalisation permet de guérir de la maladie du sommeil, France Info
- 30 November 2022 - Maladie du sommeil: résultats encourageants pour une nouvelle molécule, Le Figaro
- 30 November 2022 - New single-dose drug 95 per cent effective against sleeping sickness in adults: Lancet Study, The Economic Times
- 30 November 2022 - Un traitement contre la maladie du sommeil efficace en une dose orale unique, Le Quotidien du Médecin
- 30 November 2022 - Sanofi drug raises hopes of wiping out sleeping sickness, Bloomberg
- 30 November 2022 - Acoziborole: Investigational single-dose oral treatment raises hope for elimination of sleeping sickness in Africa
- 29 November 2022 - Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, Phase II/III trial, Lancet Infectious Diseases
- 23 November 2022 - Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up study, eBioMedicine
- 6 October 2021 - DNDi 2021 Projects of the Year recognize partners and colleagues for their work in developing new treatments for visceral leishmaniasis and sleeping sickness
- 4 September 2020 - Innovative single-dose oral sleeping sickness treatment to be co-developed by Sanofi and DNDi partnership
- 25 November 2019 - DNDi receives $29 million to fast-track the development of drugs to help eliminate sleeping sickness and river blindness
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