Identification of a moxidectin dose for 4- to 11-year-old children to support registration and potential use for onchocerciasis elimination: Results of an open-label pharmacokinetic and safety study in an onchocerciasis endemic area in Ghana

Identification of a moxidectin dose for 4- to 11-year-old children to support registration and potential use for onchocerciasis elimination: Results of an open-label pharmacokinetic and safety study in an onchocerciasis endemic area in Ghana | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Identification of a moxidectin dose for 4- to 11-year-old children to support registration and potential use for onchocerciasis elimination: Results of an open-label pharmacokinetic and safety study in an onchocerciasis endemic area in Ghana Nicholas O. Opoku, Felix Doe, Mannel E. Agbogah, Rukaya Laryea, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6342866/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jul, 2025 Read the published version in Parasites & Vectors → Version 1 posted 8 You are reading this latest preprint version Abstract Background: WHO and endemic countries target elimination of transmission of Onchocerca volvulus, the parasite causing onchocerciasis, primarily through ivermectin mass drug administration (MDA). In Africa, alternative treatment strategies are required to achieve or accelerate elimination. One of these is MDA of moxidectin, for which an 8 mg dose from age 12 years onward has received regulatory approval. This study was conducted to identify dose levels for 4-11-year-old children. Methods: An open-label, non-comparative, single-dose study in an onchocerciasis-endemic area of Ghana evaluated moxidectin pharmacokinetics and safety in four groups of nine individuals: (1) aged 12-17 years after 8 mg, (2) 8-11 years after 8 mg, (3) 8-11 years after 6 mg and (4) 4-7 years after 4 mg moxidectin. Evaluations to identify adverse events included physical examination, vital signs, haematology, clinical chemistry and 12-lead ECGs. Moxidectin plasma concentrations were measured 1, 2, 4, 8, 24 and 72 hours, and 1, 2, 4, and 12 weeks post-dose. The maximum concentration (Cmax) and area under the concentration-time curve from dosing to infinity (AUC0-∞) were obtained through non-compartmental analysis. Results: The 38 adverse events in 24 participants reflected events typically seen in the study population without treatment and were considered not moxidectin-related. Arithmetic mean (± standard deviation) Cmax (ng/mL) and AUC0-∞ (ng • h/mL) in all groups (range 84.6±18.2 to 39 118±26.5 and 2070±587 to 3910±1070, respectively) were lower than in healthy adults administered 36 mg (range 252±50.3 to 296±47 and 10835±2587 to 14972±2233, respectively), the highest and well-tolerated dose given to humans. Mean Cmax and AUC0-∞ in groups 1-3 (range 84.6±18.2 to 118±26.5 and 2920±2120 to 3910±1070, respectively) exceeded those in O. volvulus infected adults administered 8 mg (63.1±20.0 and 2738±1606, respectively). In group 4, mean Cmax (89.4±24.1) exceeded that in O. volvulus infected adults administered 8 mg (63.1±20.0). Mean AUC0-∞ (2070±587) exceeded that in O. volvulus infected adults administered 4 mg (1169±488), a dose shown to be almost as efficacious as 8 mg. Conclusions: Considering the safety data, exposures and potential MDA operational aspects, 8 mg for 8-11-year- and 4 mg for 4-7-year-old children were selected for further single-dose studies. Onchocerciasis moxidectin paediatric use doses for 4 to 11 year old children Ghana Full Text Additional Declarations Competing interest reported. ML and SK are staff of MDGH, Australia. WHO licensed all data on moxidectin at its disposal to MDGH to register moxidectin with a stringent regulatory authority and make moxidectin available to endemic countries which want to use moxidectin within their onchocerciasis elimination strategies. MDGH is the regulatory sponsor of moxidectin. ACK was staff of WHO responsible for all moxidectin-related activities in its department UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR). ACK retired from WHO in March 2023 and is continuing to work for TDR as a consultant. Supplementary Files Opokuetal.PaediatricDoseMoxidectinAdditionalFile1.pdf Cite Share Download PDF Status: Published Journal Publication published 24 Jul, 2025 Read the published version in Parasites & Vectors → Version 1 posted Editorial decision: Revision requested 03 Jun, 2025 Reviews received at journal 02 Jun, 2025 Reviewers agreed at journal 05 May, 2025 Reviewers agreed at journal 05 May, 2025 Reviewers invited by journal 16 Apr, 2025 Editor assigned by journal 02 Apr, 2025 Submission checks completed at journal 02 Apr, 2025 First submitted to journal 31 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6342866","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":448364739,"identity":"a38a78f9-4a13-4d0a-9b5b-cc6494ad7820","order_by":0,"name":"Nicholas O. 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ML and SK are staff of MDGH, Australia. WHO licensed all data on moxidectin at its disposal to MDGH to register moxidectin with a stringent regulatory authority and make moxidectin available to endemic countries which want to use moxidectin within their onchocerciasis elimination strategies. MDGH is the regulatory sponsor of moxidectin. ACK was staff of WHO responsible for all moxidectin-related activities in its department UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR). ACK retired from WHO in March 2023 and is continuing to work for TDR as a consultant.","formattedTitle":"Identification of a moxidectin dose for 4- to 11-year-old children to support registration and potential use for onchocerciasis elimination: Results of an open-label pharmacokinetic and safety study in an onchocerciasis endemic area in Ghana","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Onchocerciasis, moxidectin, paediatric use, doses for 4 to 11 year old children, Ghana","lastPublishedDoi":"10.21203/rs.3.rs-6342866/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6342866/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e WHO and endemic countries target elimination of transmission of Onchocerca volvulus, the parasite causing onchocerciasis, primarily through ivermectin mass drug administration (MDA). In Africa, alternative treatment strategies are required to achieve or accelerate elimination. One of these is MDA of moxidectin, for which an 8 mg dose from age 12 years onward has received regulatory approval. This study was conducted to identify dose levels for 4-11-year-old children. \u003cstrong\u003eMethods: \u003c/strong\u003eAn open-label, non-comparative, single-dose study in an onchocerciasis-endemic area of Ghana evaluated moxidectin pharmacokinetics and safety in four groups of nine individuals: (1) aged 12-17 years after 8 mg, (2) 8-11 years after 8 mg, (3) 8-11 years after 6 mg and (4) 4-7 years after 4 mg moxidectin. Evaluations to identify adverse events included physical examination, vital signs, haematology, clinical chemistry and 12-lead ECGs. Moxidectin plasma concentrations were measured 1, 2, 4, 8, 24 and 72 hours, and 1, 2, 4, and 12 weeks post-dose. The maximum concentration (Cmax) and area under the concentration-time curve from dosing to infinity (AUC0-∞) were obtained through non-compartmental analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The 38 adverse events in 24 participants reflected events typically seen in the study population without treatment and were considered not moxidectin-related. Arithmetic mean (± standard deviation) Cmax (ng/mL) and AUC0-∞ (ng • h/mL) in all groups (range 84.6±18.2 to 39 118±26.5 and 2070±587 to 3910±1070, respectively) were lower than in healthy adults administered 36 mg (range 252±50.3 to 296±47 and 10835±2587 to 14972±2233, respectively), the highest and well-tolerated dose given to humans. Mean Cmax and AUC0-∞ in groups 1-3 (range 84.6±18.2 to 118±26.5 and 2920±2120 to 3910±1070, respectively) exceeded those in O. volvulus infected adults administered 8 mg (63.1±20.0 and 2738±1606, respectively). In group 4, mean Cmax (89.4±24.1) exceeded that in O. volvulus infected adults administered 8 mg (63.1±20.0). Mean AUC0-∞ (2070±587) exceeded that in O. volvulus infected adults administered 4 mg (1169±488), a dose shown to be almost as efficacious as 8 mg.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Considering the safety data, exposures and potential MDA operational aspects, 8 mg for 8-11-year- and 4 mg for 4-7-year-old children were selected for further single-dose studies.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Identification of a moxidectin dose for 4- to 11-year-old children to support registration and potential use for onchocerciasis elimination: Results of an open-label pharmacokinetic and safety study in an onchocerciasis endemic area in Ghana","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 03:39:51","doi":"10.21203/rs.3.rs-6342866/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-03T10:53:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-02T23:12:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"115539846607034617620064673424733609974","date":"2025-05-05T07:19:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"203146704969986879413061664187177326351","date":"2025-05-05T06:13:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-16T11:52:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-02T07:31:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-02T04:49:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Parasites \u0026 Vectors","date":"2025-03-31T08:04:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b99cb9a1-2df4-439e-b222-fb2d5a59200b","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T16:00:17+00:00","versionOfRecord":{"articleIdentity":"rs-6342866","link":"https://doi.org/10.1186/s13071-025-06891-z","journal":{"identity":"parasites-and-vectors","isVorOnly":false,"title":"Parasites \u0026 Vectors"},"publishedOn":"2025-07-24 15:57:21","publishedOnDateReadable":"July 24th, 2025"},"versionCreatedAt":"2025-04-28 03:39:51","video":"","vorDoi":"10.1186/s13071-025-06891-z","vorDoiUrl":"https://doi.org/10.1186/s13071-025-06891-z","workflowStages":[]},"version":"v1","identity":"rs-6342866","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6342866","identity":"rs-6342866","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}