R&D MODEL & PORTFOLIO
PROJECT START: June 2014 OVERALL OBJECTIVE: Characterize and produce GMP-grade D35 to
New CL combination therapies
PROJECT START: June 2015 OVERALL OBJECTIVE: Develop an improved treatment for CL based
evaluate its protective cellular immunity and its effectiveness to treat PKDL and CL in chemotherapy combinations
2015 OBJECTIVE: Advance the pre-clinical development
on existing treatments used in combination
2015 OBJECTIVE: Obtain approval of the proposed study
CpG-D35 is being developed as a combination therapy for the treatment of complicated cutaneous leishmaniasis and post kala-azar dermal leishmaniasis (PKDL). Leishmania parasites are able to persist in host cells by evading or exploiting immune mechanisms. Modulating the immune response with CpG oligonucleotides may improve the effectiveness of chemotherapies. The project has four phases: production and characterization of GMP-grade CpG-D35, pre-clinical studies in two species to assess potential toxicities, Phase I clinical trials in healthy volunteers, and proof-of-concept clinical trials in patients for CpG-D35 and the combination of CpGD35 with chemotherapy. In 2015 IND-enabling pre-clinical safety prerequisites and service providers for entry into Phase I proof-of-concept clinical trials were identified.
MAIN PARTNERS: US FDA, USA; National Institutes of Health (NIH),
The efficacy of currently available and approved CL treatment approaches (antimonials, miltefosine, and thermotherapy) is approximately 70-75% worldwide. The safety profiles of these approaches when administrated alone is very well established. Using a combination of therapies may both improve this efficacy rate and reduce the length of treatment and rate of adverse events. A combination of one single application of thermotherapy at 50°C for 30 seconds with a 3 week course of oral miltefosine will be tested in order to gain information about safety and efficacy, with no anticipated safety problems and in a short period of time. The study protocol was finalized and submitted for review by local ethics committees in 2015; approval was received from Peru and Colombia in December 2015. It will be submitted to regulatory authorities in 2016 and patient enrolment is expected to begin the same year.
MAIN PARTNERS: Programa de Estudio y Control de Enfermedades Tropicales, Universidad de Antioquia, Medellin, Colombia; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
USA; Ohio State University, USA; Nagasaki University, Japan; University of Osaka, Japan; GeneDesign Inc., Japan
PROJECT START: September 2011 OVERALL OBJECTIVE: Develop at least one modality
of treatment for CL
2015 OBJECTIVE: Continue enrolment in the Phase Ib/II exploratory study and have an indication of the safety, PK, and efficacy
The rationale for development of a recruited at 1 site topical formulation of amphotericin B was to provide a treatment to be applied locally at the CL lesion, showing high anti-parasitic effect, but without the systemic toxicity associated with amphotericin B. A Phase Ib/II open-label, randomized, non-comparative, two-arm exploratory study is being conducted in Colombia. Initially planned to include only patients with CL caused by L. braziliensis, recruitment was widened to include patients with CL caused by L. panamensis. Enrolment of all 80 patients was completed in November 2015, and preliminary data on cure will be available in 2016.
If Anfoleish is shown to be efficacious against L. braziliensis and L. panamesis, a multi-country Phase III study will be planned in Latin America.
MAIN PARTNERS: Humax Pharmaceutical, Medellin, Colombia; Programa de Estudio y Control de Enfermedades Tropicales, Universidad de Antioquia, Medellin, Colombia
32 › DNDi Annual Report 2015