LIH’s Competence Centre for Methodology and Statistics has been involved in the Phase III trial of a new drug against the parasitic disease onchocerciasis, commonly known as river blindness. The results, published in The Lancet in January 2018, showed that moxidectin reduces parasite levels in the skin better and for longer than ivermectin, the only drug currently registered for onchocerciasis. Given that the parasites in the skin cause the morbidity and are the source for transmission, the data suggest that the use of moxidectin for onchocerciasis control could reduce time to permanent interruption of transmission compared to ivermectin.
A new drug application (NDA) for moxidectin as an oral treatment for river blindness was submitted by the not-for-profit organisation Medicines Development for Global Health (MDGH) to the US Food and Drug Administration (FDA) and qualified for priority review. The FDA designates drugs for priority review that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness and completes priority reviews within six instead of ten months, which is the standard review period.
Onchocerciasis is caused by the parasitic worm Onchocerca volvulus which is transmitted through the bites of black flies. The disease symptoms include severe skin inflammation, intense itching, enlarged lymph nodes and visual impairment that can ultimately lead to blindness. Onchocerciasis is the second leading cause of infectious blindness and the fourth leading cause of preventable blindness worldwide. Ivermectin kills the parasite life stage in the skin and eyes (microfilariae) which cause the disease symptoms and reduces, but does not prevent production of new microfilariae by the adult parasite life stage (macrofilariae) Mass drug administration with ivermectin, donated by Merck & Co, is used to control onchocerciasis as a public health problem in Africa and may even eliminate parasite transmission in some areas.
The Phase III study was a randomised, double-blind study conducted in Ghana, Liberia and the Democratic Republic of the Congo. It compared the efficacy and safety of a single oral dose of moxidectin and ivermectin in around 1500 participants. Dr Michel Vaillant, formerly Deputy Head and now Head of LIH’s Competence Centre for Methodology and Statistics (since Prof Stephen Senn’s retirement) supervised data management and conducted the statistical analysis in collaboration with Dr Christine Halleux and Dr Annette Kuesel from the Special Programme for Research and Training in Tropical Diseases (TDR) hosted at the World Health Organisation.
The study found that microfilarial loads in the skin of Onchocerciasis patients were lower after moxidectin treatment than after ivermectin treatment, often reduced to an undetectable level. Moreover, moxidectin appeared to be safe to be used in mass drug administration. The new drug is expected to reduce parasite transmission between treatment rounds more efficiently than ivermectin. Its use could accelerate the progress towards elimination of the disease and thus be beneficial for a significant part of the world’s population.
LIH’s Competence Centre for Methodology and Statistics also contributed to the FDA submission. During 2016 and 2017, it worked with Syne Qua Non, a UK Contract Research Organisation (CRO) contracted by MDGH, to qualify the database and its documentation to enable MDGH to submit the NDA.
Publication: Opoku et al., The Lancet, 2018 Single dose moxidectin versus Ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial