Advance the non-clinical and early clinical development of DNDI-0690, a selected nitroimidazole for the treatment of visceral leishmaniasis and possibly cutaneous leishmaniasis
current phase of drug development
updated 15 Feb 2023
DNDI-0690 is a nitroimidazole derivative that has shown good to excellent activity in vitro against strains of Leishmania that cause both visceral leishmaniasis and cutaneous leishmaniasis.
DNDI-0690 was identified from a library of approximately 70 nitroimidazole compounds that DNDi accessed through an agreement with the TB Alliance. While the TB Alliance investigated this class of compounds for potential TB therapies, the agreement enabled DNDi to test the compounds for potential anti-leishmanial activity.
Following its nomination as a pre-clinical candidate in September 2015, DNDI-0690 was profiled in vitro against strains of Leishmania that cause cutaneous leishmaniasis at the London School of Hygiene & Tropical Medicine and the Walter Reed Army Institute of Research.
Pre-clinical work to prepare for first-in-human studies was completed in 2019. A first Phase I study ran through early 2020 and demonstrated a favourable safety profile for single dose administration in healthy adults.
The evaluation of the safety and pharmacokinetic properties of DNDI-0690 after multiple dosing in healthy subjects was completed in 2022. Some biological abnormalities were observed in the subjects exposed to the treatment for 10 days, and additional in vitro investigations were conducted to understand the underlying mechanism. After several potential mechanisms were ruled out, the drug has been advanced for consideration for efficacy testing in leishmaniasis patients. Evaluation of the pharmacokinetic profile of the new tablet formulation will proceed when the required funding is secured.
A Phase I multiple ascending dose study of DNDI-0690 initiated in late 2020 enrolled 45 healthy adults and dosing of the drug from 5 to 10 consecutive days was completed towards the end of 2021. Results are currently being analysed and the final report is expected mid-2022. A new tablet formulation, better adapted to use in the field, has been developed and manufactured with a view to launching proof-of-concept studies in patients.
A Phase I multiple ascending dose study of DNDI-0690 was initiated in late 2020. Study completion is expected in late 2021.
A Phase I single ascending dose study in healthy volunteers was initiated in 2019; a multiple ascending dose study is planned for 2020.
A decision to progress to Phase I single ascending dose in healthy volunteers was agreed in 2018. A clinical trial application for a first-in-human study (Phase I) was submitted to UK authorities in February 2019.
A full preclinical toxicology and safety studies package was completed in 2017. The decision to progress to Phase I Single Ascending Dose in healthy volunteers was agreed in January 2018.
In 2016, DNDi activities focused on pharmaceutical development activities (drug substance and drug product development and manufacture), launching of toxicity/safety pre-IND package with dose range finding studies, as well as refinement of ADME, efficacy and safety profile to ensure a smooth transition from the pre-clinical phase to Phase I clinical phase, which should happen over the course of 2017.
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