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Harnessing potent next-generation diarylquinolines (DARQs) for long-acting injectable formulations to prevent and treat tuberculosis (TB)

This project is a collaboration between the Centre of Excellence for Long-acting Therapeutics (CELT) and Johns Hopkins University (JHU). Together we aim to develop long-acting injectable (LAI) formulations of next-generation diarylquinolines (DARQs) with and without possible companion agents for use during the continuation phase of active tuberculosis (TB) treatment and for TB preventive therapy (TPT). The goal of this NIH funded project is to develop a ‘one-shot’ DARQ LAI treatment for TPT, as well as an optimised LAI-based treatment strategy for use in the continuation phase of active TB treatment. Each should result in a sufficient data package to enable an FDA application.

Project overview

For people living with HIV (PLWH), globally TB is the most common cause of death. Effective treatment of active TB and TB prevention in PLWH could prevent many of these deaths. However, TB treatment requires 6 months of daily oral medication and TPT can require up to 9 months of tablets, but for PLWH in areas with a high TB burden continuous TPT is recommended.

TPT completion rates are low, but shorter medication regimens have a higher completion rate in both TPT and TB treatment. Improving completion rates is important as failure to complete these therapies decreases treatment efficacy and increases the chance of the development of drug resistance.

LAI options of this medication should improve completion, and therefore efficacy, as it provides a much simpler and convenient medication regimen, reducing the drug burden for both patients and health systems. Simplifying the regimen should reduce the medication burden enough that completion rates increase and the TB related deaths in PLWH decrease.

CELT's Objectives

  • Development of LAI formulations for next-generation DARQs and companion agent(s) based on a novel solid drug nanoparticles technology platform.
  • Identification of target exposures for LAI formulations and demonstration of proof-of-concept in vivo efficacy studies.
  • Nonclinical evaluation of injection site safety and tolerability, LAI stability, and CMC (Chemistry, Manufacturing and Controls) of LAI regimens to enable an IND (Investigational New Drug) application for use in TPT and/or the continuation phase of active TB treatment.
  • Non-clinical studies to confirm the sterilizing efficacy of LAI regimens for use as a single dose for TPT and for single or multiple dose treatment during the continuation phase of active TB therapy.

Awarding body

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Related publications

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