A clinical trial is being launched in three African countries of a drug that could eliminate onchocerciasis, or river blindness, one of the leading infectious causes of blindness across Africa. The drug, moxidectin, is being investigated for its potential to kill or sterilize the adult worms of Onchocerca volvulus, which cause onchocerciasis.
"This is a devastating illness that has plagued 30 African countries for centuries, in particular the populations in the most remote areas 'beyond the end of the road'," says Dr Uche Amazigo, director of the African Programme for Onchocerciasis Control (APOC). "Over 100 million people are at risk of infection with onchocerciasis in Africa and a few small areas in the Americas and Yemen."
Onchocerciasis is also called river blindness because the black fly which transmits the disease breeds in fast flowing rivers, and blindness is the most incapacitating symptom of the disease which also causes debilitating skin disease.
The development of moxidectin for onchocerciasis is being conducted through a collaboration of the Special Programme for Research and Training in Tropical Diseases (TDR), which is administered by WHO, with Wyeth Pharmaceuticals. The work ranges from the development of a formulation for human use and initial studies in healthy volunteers, to clinical studies and community studies in Africa.
TDR is building the capacity and managing the clinical trials in Africa. If the development is successful and results in a positive scientific opinion from the European Medicines Evaluation Agency, Wyeth with the assistance of WHO will request approval by regulatory authorities in the countries where onchocerciasis is endemic.
Dr Henrietta Ukwu, vice president of Wyeth Pharmaceuticals, says, "Wyeth is committed to improving access to innovative drugs and biologics around the globe including in the developing world. The moxidectin data have been promising so far, and as the programme moves into larger phase III studies, we are hopeful that moxidectin will constitute a significant advance against this devastating disease."
TDR will be working with African investigators and institutions for the trial, enrolling 1500 people at four sites in Ghana, Liberia and the Democratic Republic of the Congo. Preparation has been ongoing since 2007 and include building a clinical research centre in Lofa County in Liberia and in Nord-Kivu in the Democratic Republic of the Congo. Buildings not used since the war in Ituri in the Democratic Republic of the Congo have been renovated. All centres have been provided with necessary equipment and the research teams trained on how to conduct the trial according to international standards.
TDR's director Dr Robert Ridley says, "We work with national authorities and country partners to build research capacity and infrastructure. The training we provide to researchers and health care professionals and the experience they gather during the TDR-sponsored studies enables them to conduct other clinical research later on, strengthening the health research systems in those countries."
The trial will take place over the next two and a half years. Currently, the disease is controlled by ivermectin, which has been donated for more than 20 years by the pharmaceutical company Merck & Co. for use in onchocerciasis endemic countries. Treatment with ivermectin has enabled significant progress in the control of onchocerciasis, and currently reaches more than 60 million people in Africa annually.
However, ivermectin kills the O. volvulus larvae but not the adult worms, so annual treatments for an extended period of time (at least 11-14 years) are required to ensure disease control. Since moxidectin kills not only the larvae but also sterilizes or kills the adult worms, it has the potential to interrupt the disease transmission cycle within around six annual rounds of treatment. The drug could be distributed through the community-directed mechanisms set up in collaboration among APOC, African control programmes, and NGOs for the distribution of ivermectin.