{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:24:19Z","timestamp":1792268659796,"version":"4.4.0"},"reference-count":26,"publisher":"BMJ","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ"],"accepted":{"date-parts":[[2025,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>To evaluate the efficacy and safety of anrikefon (formerly known as HSK21542), a novel selective peripherally restricted kappa opioid receptor agonist, in patients with chronic kidney disease associated pruritus.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Design<\/jats:title>\n            <jats:p>Multicentre, double blind, randomised placebo controlled phase 3 trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Setting<\/jats:title>\n            <jats:p>50 centres in China, June 2022 to June 2024.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Participants<\/jats:title>\n            <jats:p>652 patients with moderate to severe CKD associated pruritus undergoing haemodialysis were screened: 545 were randomly assigned (1:1 ratio) to receive either anrikefon (n=275) or placebo (n=270).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Interventions<\/jats:title>\n            <jats:p>Intravenous anrikefon (0.3 \u03bcg\/kg body weight) or placebo three times weekly for 12 weeks, followed by an optional open label extension phase with anrikefon treatment for 40 weeks.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Main outcome measures<\/jats:title>\n            <jats:p>The primary endpoint was the percentage of patients achieving at least a 4 point reduction in weekly mean 24 hour worst itching intensity numerical rating scale (WI-NRS) score from baseline to week 12. Secondary outcomes were the percentage of patients achieving at least a 3 point reduction in weekly mean WI-NRS score from baseline to week 12, as well as changes in itch related quality of life from baseline using the Skindex-10 and 5-D itch scales. The change in itch related quality of life from baseline to week 40 of open label treatment was also reported using the 5-D itch scale. The safety of anrikefon was evaluated throughout the trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>\n              243\/275 (88%) patients in the anrikefon group and 254\/270 (94%) in the placebo group completed the 12 week double blind treatment. 443 subsequently entered the 40 week open label extension phase. 37% of patients in the anrikefon group showed at least a 4 point reduction in WI-NRS score at week 12 compared with 15% in the placebo group (P&lt;0.001). The percentage of patients with at least a 3 point reduction in WI-NRS score from baseline to week 12 was 51% in the anrikefon group compared with 24% in the placebo group (P&lt;0.001). The anrikefon group showed significant improvements in itch related quality of life (mean change from baseline in 5-D itch scale \u22125.3\n              <jats:italic>v<\/jats:italic>\n              \u22123.1, P&lt;0.001 and in Skindex-10 scale \u221215.2\n              <jats:italic>v<\/jats:italic>\n              \u22129.3, P&lt;0.001). Anrikefon also showed sustained long term efficacy during the open label extension phase at week 40, with persistent improvement in quality of life scores on the 5-D itch scale. Mild to moderate dizziness was more common in the anrikefon group than placebo group but without evident clinical consequences.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In patients with moderate to severe pruritus undergoing haemodialysis, anrikefon was found to be safe and resulted in a noticeable reduction in itch intensity and an improvement in itch related quality of life.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>\n              ClinicalTrials.gov\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT05135390\" ext-link-type=\"clintrialgov\">NCT05135390<\/jats:ext-link>\n              .\n            <\/jats:p>\n          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Qingdao, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Hu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Zhongshan Traditional Chinese Medicine Hospital, Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 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