Moxidectin for accelerating onchocerciasis elimination: A paediatric dose-finding study, a phase 3b trialc omparing efficacy and safety of annual and biannual moxidectin or ivermectin treatment and mathematical modelling of moxidectin and ivermectin based elimination strategies to support country policy decision

More than 100 million people live in areas in Africa endemic for onchocerciasis, an infectious disease caused by Onchocerca volvulus filarial nematodes transmitted by hematophagous blackflies. While annual community directed treatment with ivermectin (CDTI) over several decades has controlled and may even have eliminated onchocerciasis in some African foci, it is recognized that in many other areas ‘Alternative Treatment Strategies’ (ATS) are required to achieve elimination. One ATS identified by the African Programme for Onchocerciasis Control is moxidectin: in one Phase 2 and one Phase 3 single-dose treatment study in Ghana, the Democratic Republic of the Congo and Liberia, moxidectin was shown to have significantly superior efficacy relative to ivermectin, with a comparable safety profile. Modelling of moxidectin efficacy data suggests moxidectin MDA (M-MDA) could significantly accelerate progress towards onchocerciasis elimination relative to annual I-MDA.
Moxidectin development was initiated by the World Health Organization (WHO) and, until their withdrawal, conducted with Wyeth/Pfizer. Nonclinical and Phase 1-3 clinical studies supportive of regulatory registration were completed. The current moxidectin sponsor, Medicines Development for Global Health, submitted a New Drug Application (NDA) for moxidectin to the United States Food and Drug Administration in October 2017. In the proposed labelling, which supports annual treatment, moxidectin is indicated for treatment of onchocerciasis at a single 8 mg dose for individuals ≥ 12 years. One aim of this proposal is to obtain further efficacy and safety data to expand the moxidectin label and support registration in onchocerciasis-endemic countries.
M-MDA could be implemented within the structures established for CDTI. As all clinical studies to date weresingle-dose studies, knowledge gaps remain about the efficacy and safety, as well as the epidemiological impact and cost-effectiveness of repeated treatments. These gaps will be addressed by (1) a Phase 3b community-based study comparing the safety and efficacy of annual and biannual moxidectin and ivermectin treatment over 3 years and (2) mathematical modelling of time to elimination and cost-effectiveness of annual and biannual M-MDA and CDTI with two different models, both extensively used to support decision-making on onchocerciasis control and elimination strategies. Additionally, a paediatric pharmacokinetic and safety study is planned to expand labelling to include use in 4-11 year olds, who need also to be included in onchocerciasis control/elimination programmes.
Collectively, these data will address the second aim of this proposal: support policy decisions in endemiccountries on the adoption of moxidectin-based treatment strategies for onchocerciasis control and elimination.