Project: Moxidectin for accelerating onchocerciasis elimination: A paediatric dose-finding study, a phase 3b trial comparing 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 decisions

Acronym	MoxiMultiDoseMod (Reference Number: RIA2017NCT-1843)
Duration	01/08/2019 - 31/07/2024
Project Topic	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 were single-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) two Phase 3b community-based studies comparing the safety and efficacy of annual and biannual moxidectin and ivermectin treatment after a single dose of treatment or repeated doses 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 endemic countries on the adoption of moxidectin-based treatment strategies for onchocerciasis control and elimination.
Network	EDCTP2
Call	Targeting control and elimination of NIDs through clinical trials

Project partner

Number	Name	Role	Country
1	Luxembourg Institute of Health	Coordinator	Luxembourg
2	Certara UK Limited	Partner	United Kingdom
3	Communauté Evangélique au Centre de L'Afrique	Partner	Congo
5	Division Provinciale de la Sante de L'Ituri	Partner	Congo
6	Erasmus Universitair Medisch Centrum Rotterdam	Partner	Netherlands
7	Imperial College of Science Technology and Medicine	Partner	United Kingdom
8	Medicines Development for Global Health Limited	Partner	United Kingdom
9	The Royal Veterinary College University of London	Partner	United Kingdom
10	University of Antwerp	Partner	Belgium
11	University of Health and Allied Sciences - Ghana	Partner	Ghana