Introduction and Background of the Project

GeneDesign and Drugs for Neglected Diseases initiative (DNDi) seeks to find a better treatment for cutaneous leishmaniasis (CL).

About Cutaneous Leishmaniasis

There are currently no satisfactory treatments for CL, a disease that affects about one million people worldwide each year. Unlike visceral leishmaniasis, CL is not fatal but causes devastating morbidity for the patient with scaring and social stigmatism particularly for children and women, which can mark their entire life. To address the unmet need in CL, DNDi and GeneDesign are working to develop a safe and efficacious, short duration, non-invasive treatments that are affordable and field-friendly.

Treatment Challenge

Currently, recommended treatment for CL are poorly justified and have sub-optimal effectiveness and have long depended on antiquated drugs that would be considered far too toxic for introduction under modern registration systems.

Project Aim

The aim of this project is to demonstrate in an animal model if CpG D35 either alone or in combination with chemotherapy will lead to an improved leishmania infection outcome compared with chemotherapy alone. If the results of the study yield positive supporting data on the use of CpG D35, the DNDi-GeneDesign partnership will continue its activities to demonstrate the suitability of CpG D35 for progression to Phase I clinical trials.

Specific Activities

To start the study, GeneDesign will prepare the CpG D35 formulation and DNDi will identify an organisation responsible for carrying-out the in vivo study.  The study will be designed to deliver the required dose of CpG D35. Hence formulation development activities (such as solubility, tonicity adjustment and stability) will be conducted in collaboration with GeneDesign to ensure the suitability of the formulation. Following this, the "ready to use" formulation will be prepared and shipped to the study site. To assess CpG D35, 24 Asian rhesus macaques will be challenged with 10^7 L. major metacyclic promastigotes intradermally. Two sites will be inoculated, one for clinical follow-up and one for biopsy.

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Treatment Strategy

The purpose of treatment in CL is to increase the speed to complete cure, reduce scarring, and prevent relapse. One approach is to eliminate most organisms by chemotherapy, after which host immune mechanisms would control the remaining parasites. Another approach is to boost clearance by enhancing the immune mechanisms through immunotherapy. A combined approach offers the best opportunity for treatment, which if effective would reduce the chances of treatment failure, relapse, and drug resistance.

Role and Responsibility of Each Partner

The GeneDesign team, supported by DNDi and expert Professor Eddie French a formulation consultant, will be responsible in the in-vivo efficacy study for the production of the CpG D35. This includes producing the active pharmaceutical ingredient (API), designing the formulation for the in-vivo study, preparing the study supplies and carrying out the quality control and stability testing.  GeneDesign has extensive project management experience in the field of CpG oligonucleotides.  They bring experience in test suitable for toxicology and phase I/II clinical trials and in this particular project using LC-MS for most test confirmation.   

DNDi will be responsible for the overall project management, coordination, budgeting, reporting, and contracting with partners to meet the projected timelines. DNDi will also put in place the CpG D35 Advisory Committee comprised of senior representatives of DNDi, GeneDesign and relevant consultants which will convene at the beginning and conclusion of the in-vivo study.  DNDi will also submit an open source publication emanating from the study results to enable the leishmaniasis research community to benefit from the knowledge generated from the R&D team.