Work packages
The project is divided into the above series of work packages
In a Phase 2 and a Phase 3 study conducted in sub-Saharan Africa (sites in Ghana, Liberia and the Democratic Republic of the Congo), treatment with a single dose of 8 mg moxidectin was shown to be much more efficacious than ivermectin in clearing the microfilariae of O. volvulus (the worm that causes onchocerciasis) from the skin and in preventing the adult worms from producing new microfilariae. Even 12 months after treatment with moxidectin, the number of skin microfilariae was in the range of that observed just one month after ivermectin treatment. This promising new treatment could, therefore, substantially reduce transmission of the parasite between annual treatments and thus decrease the number of years of treatments required to achieve parasite elimination.
Clinical Trials
Work package 1
The effect of repeated treatments of moxidectin on the parasites has not yet been assessed. Because moxidectin has a long lasting effect on the release of microfilariae from the adult worms, giving a second dose before the adult worms have fully recovered from the effect of the previous dose may further reduce the ability of the adult worms to produce microfilariae or continue to live. Therefore, this study is one in which people will receive one of the following 4 treatment options over a two year period:
annual treatment with ivermectin (3 doses); OR
biannual treatment with ivermectin (5 doses); OR
annual treatment with moxidectin (3 doses); OR
biannual treatment with moxidectin (5 doses).
This study will test the hypothesis that annual treatment with moxidectin reduces skin microfilariae twice as well as annual ivermectin and approximately as well as biannual treatments with ivermectin and that moxidectin given twice a year reduces skin microfilariae to undetectable levels in more people and for longer.
Data from this study will then be used to model the probabilities of elimination of transmission in various transmission scenarios for each of the four treatment strategies investigated.
Study one
This large safety study will provide more data to see whether, as in the single dose clinical studies already conducted, moxidectin is shown to be safe for wide distribution to communities by community members, i.e. people who are not trained health professionals.
Study two
Work package 2
Children can become infected with O. volvulus, with the risk of infection increasing with age and intensity of transmission in their community. This leads to decreasing effectiveness of onchocerciasis control. Inclusion of children down to 4 years of age in evaluation of moxidectin for onchocerciasis elimination programmes was previously recommended by the African Programme for Onchocerciasis Control (APOC) Technical Consultative Committee.
The objective of this study is to determine the dose of moxidectin required for treatment of children 4 to 11 years, equivalent to the dose for treatment of people 12 years and older. While the Phase 3 study included adolescents aged 12 to 17 years, it did not include pharmacokinetic (PK) assessments (measurement of levels of moxidectin in the blood). PK data from the children and adolescents will be used to select an appropriate dose for children below 12 years of age.
