Research profile of moxidectin at TDR
Research on moxidectin was initiated by TDR in the late 1990s with support of the Onchocerciasis Control Programme (OCP) and the African Programme for Onchocerciasis Control (APOC), which work with TDR on research required to advance their objectives. Data from TDR sponsored research in in vitro and animal models of onchocerciasis and lymphatic filariasis showed that it was more effective than ivermectin against the parasites. Experimental data from research conducted by Fort Dodge Animal Health for moxidectin's use against animal parasites suggested that moxidectin might be safe enough for mass treatment. Based on these data, the clinical development was initiated in collaboration with the pharmaceutical company Wyeth, the owner of moxidectin at the time, and with support of OCP and APOC.
Recent APOC surveys of onchocerciasis prevalence in areas with more than 10 years of CDTI suggest that the impact of ivermectin on onchocerciasis transmission may be larger than originally anticipated and that 10-25 years of annual community-directed treatment with ivermectin (CDTI) (depending on the proportion of population treated and endemicity) may permanently interrupt transmission of the parasite in a given endemic zone. Should this be confirmed, these areas could discontinue CDTI - provided that there is no risk of 're-importing' the parasite through infected flies or people from surrounding areas.
Moxidectin may interrupt parasite transmission faster than ivermectin, thus reducing the number of years mass treatment programmes have to be sustained, allowing community, health system and donor efforts to be redirected towards other health priorities.
Studies completed to date
All pre-clinical studies and studies in healthy volunteers (Phase 1 studies) as well as the first study in humans infected with O. volvulus (Phase 2 study) have been completed.
The external expert committee (Special Project Team, SPT) which advises TDR on the development of moxidectin, met in December 2010 to review data from the Phase 1 studies and the Phase 2 study data, and recommended continuing development of moxidectin. The Phase 2 study data were discussed in March 2011 by the Technical Consultative Committee (TCC) of APOC which also recommended continuation of moxidectin development. In September 2011, TDR and APOC convened another external advisory committee (EAC) to review the Phase 2 data in light of the new data on the effect of CDTI on onchocerciasis transmission and resulting onchocerciasis control needs, taking into account other events impacting the development of moxidectin. The EAC recommended that WHO continue moxidectin development while the search for a license holder and donor is being conducted. The recommendations of the EAC were presented in September 2011 to the APOC TCC, which endorsed them.
Ongoing and planned studies
A large Phase 3 study is currently ongoing in Ghana, Liberia and the Democratic Republic of the Congo (DRC). In Ghana, the study is conducted at the Onchocerciasis Chemotherapy Research Centre which has conducted clinical research in onchocerciasis since 1977. In Liberia and DRC, three new clinical research centres were created as part of the moxidectin project:
- Liberia Institute for Biomedical Research - Clinical Research Center Bolahun
- Centre de Recherche Clinique Université Catholique de Graben in Butembo, Nord-Kivu, DRC
- Centre de Recherche en Maladies Tropicales de l'Ituri, C.R.M.T- ITURI, Hôpital Général de Référence de Rethy, Province Orientale, DRC.
A summary of the clinical research infrastructure capacity at these sites is available. The teams have completed enrolment and treatment of all subjects (1472). It is planned to complete follow up in December 2011.
Additional studies planned to obtain all data required to determine whether use of moxidectin could advance control programme objectives are: (1) a paediatric study to determine a safe dose for children; (2) a community study on the safety and efficacy of moxidectin under conditions of mass treatment; (3) evaluation of safety in case of Loa-loa co-infection as per recent advice from the EAC and APOC TCC.